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Sample records for combining polyamine depletion

  1. Role of hypusinated eukaryotic translation initiation factor 5A in polyamine depletion-induced cytostasis.

    Science.gov (United States)

    Hyvönen, Mervi T; Keinänen, Tuomo A; Cerrada-Gimenez, Marc; Sinervirta, Riitta; Grigorenko, Nikolay; Khomutov, Alex R; Vepsäläinen, Jouko; Alhonen, Leena; Jänne, Juhani

    2007-11-30

    We have earlier shown that alpha-methylated spermidine and spermine analogues rescue cells from polyamine depletion-induced growth inhibition and maintain pancreatic integrity under severe polyamine deprivation. However, because alpha-methylspermidine can serve as a precursor of hypusine, an integral part of functional eukaryotic translation initiation factor 5A required for cell proliferation, and because alpha, omega-bismethylspermine can be converted to methylspermidine, it is not entirely clear whether the restoration of cell growth is actually attributable to hypusine formed from these polyamine analogues. Here, we have used optically active isomers of methylated spermidine and spermine and show that polyamine depletion-induced acute cytostasis in cultured cells could be reversed by all the isomers of the methylpolyamines irrespective of whether they served or not as precursors of hypusine. In transgenic rats with activated polyamine catabolism, all the isomers similarly restored liver regeneration and reduced plasma alpha-amylase activity associated with induced pancreatitis. Under the above experimental conditions, the (S, S)- but not the (R, R)-isomer of bismethylspermine was converted to methylspermidine apparently through the action of spermine oxidase strongly preferring the (S, S)-isomer. Of the analogues, however, only (S)-methylspermidine sustained cell growth during prolonged (more than 1 week) inhibition of polyamine biosynthesis. It was also the only isomer efficiently converted to hypusine, indicating that deoxyhypusine synthase likewise possesses hidden stereospecificity. Taken together, the results show that growth inhibition in response to polyamine depletion involves two phases, an acute and a late hypusine-dependent phase.

  2. Polyamine Depletion Attenuates Isoproterenol-Induced Hypertrophy and Endoplasmic Reticulum Stress in Cardiomyocytes

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    Yan Lin

    2014-10-01

    Full Text Available Background/Aim: Polyamines (putrescine, spermidine and spermine play an essential role in cell growth, differentiation and apoptosis. Hypertrophy is accompanied by an increase in polyamine synthesis and endoplasmic reticulum stress (ERS in cardiomyocytes. The present study was undertaken to elucidate the molecular interactions between polyamines, ERS and cardiac hypertrophy. Methods: Myocardial hypertrophy was simulated by incubating cultured neonatal rat cardiomyocytes in 100 nM isoproterenol (ISO. Polyamine deletion was achieved using 0.5 mM difluoromethylornithine (DFMO. Hypertrophy was estimated using cell surface area measurements, total protein concentrations and atrial natriuretic peptide (ANP gene expression. Apoptosis was measured using flow cytometry and transmission electron microscopy. Expression of ornithine decarboxylase (ODC and spermidine/spermine N1-acetyltransferase (SSAT were analyzed via real-time PCR and Western blotting. Protein expression of ERS and apoptosis factors were analyzed using Western blotting. Results: DFMO (0.5 mM and 2 mM treatments significantly attenuated hypertrophy and apoptosis induced by ISO in cardiomyocytes. DFMO also decreased lactate dehydrogenase (LDH and malondialdehyde (MDA level in the culture medium. In addition, DFMO (0.5 mM down regulated the expression of ODC, glucose-regulated protein 78 (GRP78, C/EBP homologous protein (CHOP, cleaved caspase-12, and Bax and up regulated the expression of SSAT and Bcl-2. Finally, these changes were partly reversed by the addition of exogenous putrescine (0.5 mM. Conclusion: The data presented here suggest that polyamine depletion could inhibit cardiac hypertrophy and apoptosis, which is closely related to the ERS pathway.

  3. Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy.

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    Xie, Ying; Murray-Stewart, Tracy; Wang, Yazhe; Yu, Fei; Li, Jing; Marton, Laurence J; Casero, Robert A; Oupický, David

    2017-01-28

    Combination of anticancer drugs with therapeutic microRNA (miRNA) has emerged as a promising anticancer strategy. However, the promise is hampered by a lack of desirable delivery systems. We report on the development of self-immolative nanoparticles capable of simultaneously delivering miR-34a mimic and targeting dysregulated polyamine metabolism in cancer. The nanoparticles were prepared from a biodegradable polycationic prodrug, named DSS-BEN, which was synthesized from a polyamine analog N(1),N(11)-bisethylnorspermine (BENSpm). The nanoparticles were selectively disassembled in the cytoplasm where they released miRNA. Glutathione (GSH)-induced degradation of self-immolative linkers released BENSpm from the DSS-BEN polymers. MiR-34a mimic was effectively delivered to cancer cells as evidenced by upregulation of intracellular miR-34a and downregulation of Bcl-2 as one of the downstream targets of miR-34a. Intracellular BENSpm generated from the degraded nanoparticles induced the expression of rate-limiting enzymes in polyamine catabolism (SMOX, SSAT) and depleted cellular natural polyamines. Simultaneous regulation of polyamine metabolism and miR-34a expression by DSS-BEN/miR-34a not only enhanced cancer cell killing in cultured human colon cancer cells, but also improved antitumor activity in vivo. The reported findings validate the self-immolative nanoparticles as delivery vectors of therapeutic miRNA capable of simultaneously targeting dysregulated polyamine metabolism in cancer, thereby providing an elegant and efficient approach to combination nanomedicines.

  4. Polyamines

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    Marton, Laurence J.

    The polyamines spermidine [NH2(CH2)3NH(CH2)4NH2] and spermine [NH2(CH2)3NH(CH2)4NH(CH2)3NH2] and their diamine precursor, putrescine [NH2(CH2)4NH2], have been the subject of intense study relative to their potential as tumor markers during the past decade (1). These compounds have been implicated in numerous biochemical reactions and have been clearly associated with cellular growth processes. A number of publications have reviewed our present knowledge regarding these compounds, including their relationship to human disease (2-6).

  5. Polyamine depletion enhances the roscovitine-induced apoptosis through the activation of mitochondria in HCT116 colon carcinoma cells.

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    Arısan, Elif Damla; Coker, Ajda; Palavan-Ünsal, Narçin

    2012-02-01

    Small molecule inhibitors of cyclin-dependent kinases (CDKs) show high therapeutic potential in various cancer types which are characterized by the accumulation of transformed cells due to impaired apoptotic machinery. Roscovitine, a CDK inhibitor showed to be a potent apoptotic inducer in several cancer cells. Polyamines, putrescine, spermidine and spermine, are biogenic amines involved in many cellular processes, including apoptosis. In this study, we explored the potential role of polyamines in roscovitine-induced apoptosis in HCT116 colon cancer cells. Roscovitine induced apoptosis by activating mitochondrial pathway caspases and modulating the expression of Bcl-2 family members. Depletion of polyamines by treatment with difluoromethylornithine (DFMO) increased roscovitine-induced apoptosis. Transient silencing of ornithine decarboxylase, polyamine biosynthesis enzyme and special target of DFMO also increased roscovitine-induced apoptosis in HCT116 cells. Interestingly, additional putrescine treatment was found pro-apoptotic due to the presence of non-functional ornithine decarboxylase (ODC). Finally, roscovitine altered polyamine catabolic pathway and led to decrease in putrescine and spermidine levels. Therefore, the metabolic regulation of polyamines may dictate the power of roscovitine induced apoptotic responses in HCT116 colon cancer cells.

  6. Depletion of polyamines prevents the neurotrophic activity of the GABA-agonist THIP in cultured rat cerebellar granule cells

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    Abraham, J H; Hansen, Gert Helge; Seiler, N

    1993-01-01

    Effects of polyamine depletion by alpha-difluoromethylornithine (DFMO) were studied on the GABA-agonist mediated enhancement of the morphological development of cultured rat cerebellar granule cells. An increase in the number of neurite extending cells and in the cytoplasmic density of organelles...... endoplasmic reticulum, Golgi apparatus and different types of vesicles was prevented by the exposure to DFMO....

  7. Increased toxicity of a trinuclear Pt-compound in a human squamous carcinoma cell line by polyamine depletion

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    Kjellström Johan

    2012-05-01

    Full Text Available Abstract Background Mononuclear platinum anticancer agents hold a pivotal place in the treatment of many forms of cancers, however, there is a potential to improve response to evade resistance development and toxic side effects. BBR3464 is a promising trinuclear platinum anticancer agent, which is a polyamine mimic. The aim was to investigate the influence of polyamine pool reduction on the cytotoxic effects of the trinuclear platinum complex BBR3464 and cisplatin. Polyamine pool reduction was achieved by treating cells with either the polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO or the polyamine analogue N1,N11-diethylnorspermine (DENSPM. Methods A human squamous cell carcinoma cell line, LU-HNSCC-4, established from a primary head and neck tumour was used to evaluate cellular effects of each drug alone or combinations thereof. High-performance liquid-chromatography was used to quantify intracellular polyamine contents. Inductively coupled mass spectroscopy was used to quantify intracellular platinum uptake. Cells were exposed to DFMO or DENSPM during 48 h at concentrations ranging from 0 to 5 mM or 0 to 10 μM, respectively. Thereafter, non-treated and treated cells were exposed to cisplatin or BBR3464 during 1 h at concentrations ranging from 0 to 100 μM. A 96-well assay was used to determine cytotoxicity after five days after treatment. Results The cytotoxic effect of BBR3464 on LU-HNSCC-4 cells was increased after cells were pre-treated with DENSPM or DFMO, and the interaction was found to be synergistic. In contrast, the interaction between cisplatin and DFMO or DENSPM was near-additive to antagonistic. The intracellular levels of the polyamines putrescine and spermidine were decreased after treatment with DFMO, and treatment with DENSPM resulted in an increase in putrescine level and concomitant decrease in spermidine and spermine levels. The uptake of BBR3464 was significantly increased after pre

  8. Depletion of the polyamines spermidine and spermine by overexpression of spermidine/spermine N¹-acetyltransferase 1 (SAT1) leads to mitochondria-mediated apoptosis in mammalian cells.

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    Mandal, Swati; Mandal, Ajeet; Park, Myung Hee

    2015-06-15

    The polyamines putrescine, spermidine and spermine are intimately involved in the regulation of cellular growth and viability. Transduction of human embryonic kidney (HEK) 293T cells with an adenovirus encoding a key polyamine catabolic enzyme, spermidine N¹-acetyltransferase 1 (SSAT1)/SAT1 (AdSAT1), leads to a rapid depletion of spermidine and spermine, arrest in cell growth and a decline in cell viability. Annexin V/propidium iodide FACS analyses, terminal uridine nucleotide end-labelling (TUNEL) and caspase 3 assays showed a clear indication of apoptosis in AdSAT1-transduced cells (at 24-72 h), but not in cells transduced with GFP-encoding adenovirus (AdGFP). Apoptosis in the polyamine-depleted cells occurs by the mitochondrial intrinsic pathway, as evidenced by loss of mitochondrial membrane potential, increase in pro-apoptotic Bax, decrease in anti-apoptotic Bcl-xl, Bcl2 and Mcl-1 and release of cytochrome c from mitochondria, upon transduction with AdSAT1. Moreover, TEM images of AdSAT1-transduced cells revealed morphological changes commonly associated with apoptosis, including cell shrinkage, nuclear fragmentation, mitochondrial alteration, vacuolization and membrane blebbing. The apoptosis appears to result largely from depletion of the polyamines spermidine and spermine, as the polyamine analogues α-methylspermidine (α-MeSpd) and N¹,N¹²-dimethylspermine (Me₂Spm) that are not substrates for SAT1 could partially restore growth and prevent apoptosis of AdSAT1-transduced cells. Inhibition of polyamine oxidases did not restore the growth of AdSAT1-transduced cells or block apoptosis, suggesting that the growth arrest and apoptosis were not induced by oxidative stress resulting from accelerated polyamine catabolism. Taken together, these data provide strong evidence that the depletion of the polyamines spermidine and spermine leads to mitochondria-mediated apoptosis. © The Authors Journal compilation © 2015 Biochemical Society.

  9. Induced ATF-2 represses CDK4 transcription through dimerization with JunD inhibiting intestinal epithelial cell growth after polyamine depletion.

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    Xiao, Lan; Rao, Jaladanki N; Zou, Tongtong; Liu, Lan; Yu, Ting-Xi; Zhu, Xiao-Yu; Donahue, James M; Wang, Jian-Ying

    2010-05-01

    Intestinal epithelium is a rapidly self-renewing tissue in the body, and its homeostasis is tightly regulated by numerous factors including polyamines. Decreased levels of cellular polyamines increase activating transcription factor (ATF)-2, but the exact role and mechanism of induced ATF-2 in the regulation of intestinal epithelial cell (IEC) growth remain elusive. Cyclin-dependent kinase (CDK) 4 is necessary for the G1-to-S phase transition during the cell cycle, and its expression is predominantly controlled at the transcription level. Here, we reported that induced ATF-2 following polyamine depletion repressed CDK4 gene transcription in IECs by increasing formation of the ATF-2/JunD heterodimers. ATF-2 formed complexes with JunD as measured by immunoprecipitation using the ATF-2 and JunD antibodies and by glutathione S-transferase (GST) pull-down assays using GST-ATF-2 fusion proteins. Studies using various mutants of GST-ATF-2 revealed that formation of the ATF-2/JunD dimers depended on the COOH-terminal basic region-leucine zipper domain of ATF-2. Polyamine depletion increased ATF-2/JunD complex and inhibited CDK4 transcription as indicated by a decrease in the levels of CDK4-promoter activity and its mRNA. ATF-2 silencing not only prevented inhibition of CDK4 transcription in polyamine-deficient cells but also abolished repression of CDK4 expression induced by ectopic JunD overexpression. ATF-2 silencing also promoted IEC growth in polyamine-depleted cells. These results indicate that induced ATF-2/JunD association following polyamine depletion represses CDK4 transcription, thus contributing to the inhibition of IEC growth.

  10. Phase I/II clinical trial of 2-Difluoromethylornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma

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    Skorupski, Katherine A.; O'Brien, Thomas G; Guerrero, Teri; Rodriguez, Carlos O.; Burns, Mark R.

    2011-01-01

    Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumor regression in mouse models of SCC. The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase inhibitor, DFMO, and to determine whether this therapy results in reduction in tumor polyamine levels. Thirteen cats with oral SCC received both drugs orally ...

  11. The polyamine inhibitor alpha-difluoromethylornithine modulates hippocampus-dependent function after single and combined injuries.

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    Susanna Rosi

    Full Text Available Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury.

  12. The mechanism by which MEK/ERK regulates JNK and p38 activity in polyamine depleted IEC-6 cells during apoptosis.

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    Bavaria, Mitul N; Jin, Shi; Ray, Ramesh M; Johnson, Leonard R

    2014-03-01

    Polyamine-depletion inhibited apoptosis by activating ERK1/2, while, preventing JNK1/2 activation. MKP-1 knockdown by SiRNA increased ERK1/2, JNK1/2, and p38 phosphorylation and apoptosis. Therefore, we predicted that polyamines might regulate MKP1 via MEK/ERK and thereby apoptosis. We examined the role of MEK/ERK in the regulation of MKP1 and JNK, and p38 activities and apoptosis. Inhibition of MKP-1 activity with a pharmacological inhibitor, sanguinarine (SA), increased JNK1/2, p38, and ERK1/2 activities without causing apoptosis. However, pre-activation of these kinases by SA significantly increased camptothecin (CPT)-induced apoptosis suggesting different roles for MAPKs during survival and apoptosis. Inhibition of MEK1 activity prevented the expression of MKP-1 protein and augmented CPT-induced apoptosis, which correlated with increased activities of JNK1/2, caspases, and DNA fragmentation. Polyamine depleted cells had higher levels of MKP-1 protein and decreased JNK1/2 activity and apoptosis. Inhibition of MEK1 prevented MKP-1 expression and increased JNK1/2 and apoptosis. Phospho-JNK1/2, phospho-ERK2, MKP-1, and the catalytic subunit of PP2Ac formed a complex in response to TNF/CPT. Inactivation of PP2Ac had no effect on the association of MKP-1 and JNK1. However, inhibition of MKP-1 activity decreased the formation of the MKP-1, PP2Ac and JNK complex. Following inhibition by SA, MKP-1 localized in the cytoplasm, while basal and CPT-induced MKP-1 remained in the nuclear fraction. These results suggest that nuclear MKP-1 translocates to the cytoplasm, binds phosphorylated JNK and p38 resulting in dephosphorylation and decreased activity. Thus, MEK/ERK activity controls the levels of MKP-1 and, thereby, regulates JNK activity in polyamine-depleted cells.

  13. Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma.

    Science.gov (United States)

    Skorupski, K A; O'Brien, T G; Guerrero, T; Rodriguez, C O; Burns, M R

    2011-12-01

    Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumour regression in mouse models of squamous cell carcinoma (SCC). The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase (ODC) inhibitor, DFMO, and to determine whether this therapy results in reduction in tumour polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumour biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose (MTD) of MQT 1426 when combined with DFMO was determined. Dose-limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, two cats experienced objective tumour regression and six cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted.

  14. Polyamine toxins

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Jensen, Lars S; Vogensen, Stine B

    2005-01-01

    Polyamine toxins, isolated from spiders and wasps, have been used as pharmacological tools for the study of ionotropic receptors, but their use have so far been hampered by their lack of selectivity. In this mini-review, we describe how careful synthetic modification of native polyamine toxins have...

  15. Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

    NARCIS (Netherlands)

    L. van Zuylen; C. Mueller; J. Verweij (Jaap); J.A. Ledermann; J. Bridgewater; A. Sparreboom (Alex); F.A.L.M. Eskens (Ferry); P. de Bruijn (Peter); I. Sklenar; A.S.Th. Planting (André); L. Choi; D. Bootle

    2004-01-01

    textabstractPURPOSE: The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients.

  16. Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases

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    Wesley H. Brooks

    2013-04-01

    Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.

  17. Polyamine analogues targeting epigenetic gene regulation.

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    Huang, Yi; Marton, Laurence J; Woster, Patrick M; Casero, Robert A

    2009-11-04

    Over the past three decades the metabolism and functions of the polyamines have been actively pursued as targets for antineoplastic therapy. Interactions between cationic polyamines and negatively charged nucleic acids play a pivotal role in DNA stabilization and RNA processing that may affect gene expression, translation and protein activity. Our growing understanding of the unique roles that the polyamines play in chromatin regulation, and the discovery of novel proteins homologous with specific regulatory enzymes in polyamine metabolism, have led to our interest in exploring chromatin remodelling enzymes as potential therapeutic targets for specific polyamine analogues. One of our initial efforts focused on utilizing the strong affinity that the polyamines have for chromatin to create a backbone structure, which could be combined with active-site-directed inhibitor moieties of HDACs (histone deacetylases). Specific PAHAs (polyaminohydroxamic acids) and PABAs (polyaminobenzamides) polyamine analogues have demonstrated potent inhibition of the HDACs, re-expression of p21 and significant inhibition of tumour growth. A second means of targeting the chromatin-remodelling enzymes with polyamine analogues was facilitated by the recent identification of flavin-dependent LSD1 (lysine-specific demethylase 1). The existence of this enzyme demonstrated that histone lysine methylation is a dynamic process similar to other histone post-translational modifications. LSD1 specifically catalyses demethylation of mono- and di-methyl Lys4 of histone 3, key positive chromatin marks associated with transcriptional activation. Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1. Cellular inhibition of LSD1 by these unique compounds led to the re-activation of multiple epigenetically silenced genes important in tumorigenesis. The use of

  18. Polyamine catabolism and disease.

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    Casero, Robert A; Pegg, Anthony E

    2009-07-15

    In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis and the response to stressful stimuli, and contribute to the aetiology of several pathological states, including cancer. The highly inducible enzymes SSAT (spermidine/spermine N1-acetyltransferase) and SMO (spermine oxidase) and the generally constitutively expressed APAO (N1-acetylpolyamine oxidase) appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique druggable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homoeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathological states. The activity of SSAT provides substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal of the present review is to cover those aspects of polyamine catabolism that have an impact on disease aetiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.

  19. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

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    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  20. Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines

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    Üçpunar, Habibe K.; Svensson, Thomas; Quillery, Elsa; Gompel, Nicolas; Ignell, Rickard; Grunwald Kadow, Ilona C.

    2016-01-01

    The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detrimental effects on health, cognitive function, reproduction, and lifespan. Here, we show that a diet high in polyamine is beneficial and increases reproductive success of flies, and we unravel the sensory mechanisms that attract Drosophila to polyamine-rich food and egg-laying substrates. Using a combination of behavioral genetics and in vivo calcium imaging, we demonstrate that Drosophila uses multisensory detection to find and evaluate polyamines present in overripe and fermenting fruit, their favored feeding and egg-laying substrate. In the olfactory system, two coexpressed ionotropic receptors (IRs), IR76b and IR41a, mediate the long-range attraction to the odor. In the gustatory system, multimodal taste sensation by IR76b receptor and GR66a bitter receptor neurons is used to evaluate quality and valence of the polyamine providing a mechanism for the fly’s high attraction to polyamine-rich and sweet decaying fruit. Given their universal and highly conserved biological roles, we propose that the ability to evaluate food for polyamine content may impact health and reproductive success also of other animals including humans. PMID:27145030

  1. Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines.

    Directory of Open Access Journals (Sweden)

    Ashiq Hussain

    2016-05-01

    Full Text Available The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detrimental effects on health, cognitive function, reproduction, and lifespan. Here, we show that a diet high in polyamine is beneficial and increases reproductive success of flies, and we unravel the sensory mechanisms that attract Drosophila to polyamine-rich food and egg-laying substrates. Using a combination of behavioral genetics and in vivo calcium imaging, we demonstrate that Drosophila uses multisensory detection to find and evaluate polyamines present in overripe and fermenting fruit, their favored feeding and egg-laying substrate. In the olfactory system, two coexpressed ionotropic receptors (IRs, IR76b and IR41a, mediate the long-range attraction to the odor. In the gustatory system, multimodal taste sensation by IR76b receptor and GR66a bitter receptor neurons is used to evaluate quality and valence of the polyamine providing a mechanism for the fly's high attraction to polyamine-rich and sweet decaying fruit. Given their universal and highly conserved biological roles, we propose that the ability to evaluate food for polyamine content may impact health and reproductive success also of other animals including humans.

  2. Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines.

    Science.gov (United States)

    Hussain, Ashiq; Zhang, Mo; Üçpunar, Habibe K; Svensson, Thomas; Quillery, Elsa; Gompel, Nicolas; Ignell, Rickard; Grunwald Kadow, Ilona C

    2016-05-01

    The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detrimental effects on health, cognitive function, reproduction, and lifespan. Here, we show that a diet high in polyamine is beneficial and increases reproductive success of flies, and we unravel the sensory mechanisms that attract Drosophila to polyamine-rich food and egg-laying substrates. Using a combination of behavioral genetics and in vivo calcium imaging, we demonstrate that Drosophila uses multisensory detection to find and evaluate polyamines present in overripe and fermenting fruit, their favored feeding and egg-laying substrate. In the olfactory system, two coexpressed ionotropic receptors (IRs), IR76b and IR41a, mediate the long-range attraction to the odor. In the gustatory system, multimodal taste sensation by IR76b receptor and GR66a bitter receptor neurons is used to evaluate quality and valence of the polyamine providing a mechanism for the fly's high attraction to polyamine-rich and sweet decaying fruit. Given their universal and highly conserved biological roles, we propose that the ability to evaluate food for polyamine content may impact health and reproductive success also of other animals including humans.

  3. Polyamines in Human Breast Milk

    OpenAIRE

    Nihal Büyükuslu

    2015-01-01

    Human milk is the ideal food for all newborns and infants. It involves macro nutrients and functional compounds for growth and development. The composition of breast milk differs between preterm and term milk. Polyamines are essential for cell proliferation and differentiation. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as food, and intestinal microbiota. Breast milk is the first source of exogenous polyamines...

  4. Polyamines in plant physiology

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    Galston, A. W.; Sawhney, R. K.

    1990-01-01

    The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.

  5. Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

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    Julie Harvengt

    2014-01-01

    Full Text Available A 1-year-old girl born to consanguineous parents presented with unexplained liver failure, leading to transplantation at 19 months. Subsequent partial splenectomy for persistent cytopenia showed the presence of foamy cells, and Gaucher disease was confirmed by homozygosity for the p.Leu483Pro mutation in the GBA gene. She was treated by enzyme replacement therapy (ERT. Clinical follow-up showed mild developmental delay, strabismus, nystagmus and oculomotor apraxia. Biochemical studies revealed multiple respiratory chain deficiencies and a mosaic pattern of deficient complex IV immunostaining in liver and fibroblast. Molecular analysis identified a mtDNA depletion syndrome due to the homozygous p.Pro98Leu mutation in MPV17. A younger sister unaffected by mtDNA depletion, presented with pancytopenia and hepatosplenomegaly. ERT for Gaucher disease resulted in visceral normalization without any neurological symptom. A third sister, affected by both conditions, had marked developmental delay, strabismus and ophthalmoplegia but no liver cirrhosis. In conclusion, intrafamilal variability occurs in MPV17-related disease. The combined pathological effect of Gaucher and mitochondrial diseases can negatively impact neurological and liver functions and influence the outcome in consanguineous families. The immunocytochemical staining of OXPHOS protein in tissues and cultured cells is a powerful tool revealing mosaic pattern of deficiency pointing to mtDNA-related mitochondrial disorders.

  6. Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention.

    Science.gov (United States)

    Battaglia, Valentina; DeStefano Shields, Christina; Murray-Stewart, Tracy; Casero, Robert A

    2014-03-01

    Polyamines, including spermine, spermidine, and the precursor diamine, putrescine, are naturally occurring polycationic alkylamines that are required for eukaryotic cell growth, differentiation, and survival. This absolute requirement for polyamines and the need to maintain intracellular levels within specific ranges require a highly regulated metabolic pathway primed for rapid changes in response to cellular growth signals, environmental changes, and stress. Although the polyamine metabolic pathway is strictly regulated in normal cells, dysregulation of polyamine metabolism is a frequent event in cancer. Recent studies suggest that the polyamine catabolic pathway may be involved in the etiology of some epithelial cancers. The catabolism of spermine to spermidine utilizes either the one-step enzymatic reaction of spermine oxidase (SMO) or the two-step process of spermidine/spermine N (1)-acetyltransferase (SSAT) coupled with the peroxisomal enzyme N (1)-acetylpolyamine oxidase. Both catabolic pathways produce hydrogen peroxide and a reactive aldehyde that are capable of damaging DNA and other critical cellular components. The catabolic pathway also depletes the intracellular concentrations of spermidine and spermine, which are free radical scavengers. Consequently, the polyamine catabolic pathway in general and specifically SMO and SSAT provide exciting new targets for chemoprevention and/or chemotherapy.

  7. Polyamines in tea processing.

    Science.gov (United States)

    Palavan-Unsal, Narcin; Arisan, Elif Damla; Terzioglu, Salih

    2007-06-01

    The distribution of dietary polyamines, putrescine, spermidine and spermine, was determined during processing of Camellia sinensis. Black tea manufacture is carried by a series of processes on fresh tea leaves involving withering, rolling, fermentation, drying and sieving. The aim of this research was to determine the effect of tea processing on the polyamine content in relation with antioxidant enzymes, superoxide dismutase, lipid peroxidase and glutathione peroxidase. Before processing, the spermine content was much higher than the putrescine and spermidine content in green tea leaves. Spermine was significantly decreased during processing while the putrescine and spermine contents increased during withered and rolling and decreased in the following stages. The superoxide dismutase activity increased at the withering stage and declined during processing. The transcript level of the polyamine biosynthesis-responsible enzyme ornithine decarboxylase was reduced during each processing step. This study reveals the importance of protection of nutritional compounds that are essential for health during the manufacturing process.

  8. The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

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    Malloy Mary J

    2006-07-01

    Full Text Available Abstract Background Lipoprotein Lipase (LPL, a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH. Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined. Results We found evidence of significant allelic (447Xcontrol: 0.130 vs. 447Xcase: 0.031, χ2 = 29.085; 1df; p 2 = 26.09; 1df; p Conclusion These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors.

  9. Say what? The activity of the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO) in chemoprevention is a result of reduced thymidine pools?

    Science.gov (United States)

    Casero, Robert A.

    2013-01-01

    Summary In the current issue of Cancer Discovery, Witherspoon, Lipkin and colleagues use an unbiased metabolite profiling approach to study the effects of polyamine depletion by DFMO in colon cancer cells. Their surprising findings indicate that it is a decrease in thymidine pools resulting from altered tetrahydrofolate availability rather than decreases in polyamines that produce cytostasis. PMID:24019331

  10. Say what? The activity of the polyamine biosynthesis inhibitor difluoromethylornithine in chemoprevention is a result of reduced thymidine pools?

    Science.gov (United States)

    Casero, Robert A

    2013-09-01

    In this issue of Cancer Discovery, Witherspoon and colleagues use an unbiased metabolite profiling approach to study the effects of polyamine depletion by 2-difluoromethylornithine in colon cancer cells. Their surprising findings indicate that it is a decrease in thymidine pools resulting from altered tetrahydrofolate availability rather than decreases in polyamines that produces cytostasis.

  11. Synthesis of a Versatile Building Block Combining Cyclen-derivative DO3A with a Polyamine via a Rigid Spacer

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    Zdeněk Trávníček

    2013-11-01

    Full Text Available The five-step synthesis of a polydentate building block combining a cyclen-based macrocycle (DO3A with N-(2-aminoethylpropane-1,3-diamine, which are linked through the xylylen moiety as a rigid C-spacer is described. These two molecular parts were coupled by subsequent bromine atom substitution in 1,4-bis(bromomethylbenzene. First, N-(2-aminoethylpropane-1,3-diamine was protected by phthaloyl moieties and then it was reacted with 1,4-bis(bromomethylbenzene to form (2-phthalimidoethyl(3-phthalimido-prop-1-yl(4-bromomethylbenzylamine (2. This compound underwent a substitution reaction with DO3A in the form of its tert-butyl esters leading to the intermediate 1-{4-[(2-phthalimidoethyl(3-phthalimidoprop-1-ylaminomethyl]phenylmethyl}-4,7,10-tris(t-butoxy-carbonylmethyl-1,4,7,10-tetraazacyclododecane (3. The phthaloyl as well as the t-butyl protecting groups were removed in the next two reaction steps to form the final product 1-{4-[(2-aminoethyl(3-aminoprop-1-ylaminomethyl]phenylmethyl}-4,7,10-tris(carboxy-methyl-1,4,7,10-tetraazacyclododecane (5. The intermediates 1–4 as well as the final product 5 were characterized by elemental analysis, mass spectrometry, and multinuclear (1H and 13C and two-dimensional NMR spectroscopy. The final product 5 could serve as a potential building block in subsequent syntheses of binuclear complexes of lanthanides and/or transition metals.

  12. Polyamines are oncometabolites that regulate the LIN28/let-7 pathway in colorectal cancer cells.

    Science.gov (United States)

    Paz, Edwin A; LaFleur, Bonnie; Gerner, Eugene W

    2014-02-01

    Polyamine metabolism is a highly coordinated process that is essential for normal development and neoplastic growth in mammals. Although polyamine metabolism is a validated pathway for prevention of carcinogenesis, the mechanisms by which polyamines elicit their tumorigenic effects are poorly understood. In this study, we investigated the role of polyamine metabolism in colon cancer by screening a non-coding RNA (ncRNA) platform to identify polyamine responsive signaling nodes. We report that multiple non-coding RNAs are altered by polyamine depletion including induction of microRNA (miRNA) let-7i, a member of the tumor suppressive let-7 family. The let-7 family targets several RNAs for translational repression, including the growth-associated transcription factor HMGA2 and is negatively regulated by the pluripotency factor LIN28. Depletion of polyamines using difluoromethylornithine (DFMO) or genetic knockdown of the polyamine-modified eukaryotic translation initiation factor 5A isoforms 1 and 2 (eIF5A1/2) resulted in robust reduction of both HMGA2 and LIN28. Locked nucleic acid (LNA) oligonucleotides targeting the seed region of the let-7 family rescued the expression of HMGA2, but not LIN28, in both DFMO-treated and eIF5A1/2 knockdown cultures. Our findings suggest that polyamines are oncometabolites that influence specific aspects of tumorigenesis by regulating pluripotency associated factors, such as LIN28, via an eIF5A-dependent but let-7-independent mechanism while the expression of proliferation-related genes regulated by let-7, such as HMGA2, is mediated through microRNA mediated repression. Therefore, manipulating polyamine metabolism may be a novel method of targeting the LIN28/let-7 pathway in specific disease states. © 2013 Wiley Periodicals, Inc.

  13. Combined effects of alpha particles and depleted uranium on Zebrafish (Danio rerio) embryos

    Science.gov (United States)

    Ng, Candy Y.P.; Pereira, Sandrine; Cheng, Shuk Han; Adam-Guillermin, Christelle; Garnier-Laplace, Jacqueline; Yu, Kwan Ngok

    2016-01-01

    The combined effects of low-dose or high-dose alpha particles and depleted uranium (DU) in Zebrafish (Danio rerio) embryos were studied. Three schemes were examined—(i) [ILUL]: 0.44 mGy alpha-particle dose + 10 µg/l DU exposure, (ii) [IHUH]: 4.4 mGy alpha-particle dose + 100 µg/l DU exposure and (iii) [IHUL]: 4.4 mGy alpha-particle dose + 10 µg/l DU exposure—in which Zebrafish embryos were irradiated with alpha particles at 5 h post fertilization (hpf) and/or exposed to uranium at 5–6 hpf. The results were also compared with our previous work, which studied the effects of [ILUH]: 0.44 mGy alpha-particle dose + 100 µg/l DU exposure. When the Zebrafish embryos developed to 24 hpf, the apoptotic signals in the entire embryos, used as the biological endpoint for this study, were quantified. Our results showed that [ILUL] and [IHUL] led to antagonistic effects, whereas [IHUH] led to an additive effect. The effect found for the previously studied case of [ILUH] was difficult to define because it was synergistic with reference to the 100 µg/l DU exposure, but it was antagonistic with reference to the 0.44 mGy alpha-particle dose. All the findings regarding the four different schemes showed that the combined effects critically depended on the dose response to each individual stressor. We also qualitatively explained these findings in terms of promotion of early death of cells predisposed to spontaneous transformation by alpha particles, interacting with the delay in cell death resulting from various concentrations of DU exposure. PMID:26937024

  14. Polyamines are present in mast cell secretory granules and are important for granule homeostasis.

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    Gianni García-Faroldi

    Full Text Available BACKGROUND: Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG present within the granules. Polyamines (putrescine, spermidine and spermine are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules. METHODOLOGY/PRINCIPAL FINDINGS: Spermidine was released by mouse bone marrow derived mast cells (BMMCs after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

  15. Modulation of protein synthesis by polyamines.

    Science.gov (United States)

    Igarashi, Kazuei; Kashiwagi, Keiko

    2015-03-01

    Polyamines are ubiquitous small basic molecules that play important roles in cell growth and viability. Since polyamines mainly exist as a polyamine-RNA complex, we looked for proteins whose synthesis is preferentially stimulated by polyamines at the level of translation, and thus far identified 17 proteins in Escherichia coli and 6 proteins in eukaryotes. The mechanisms of polyamine stimulation of synthesis of these proteins were investigated. In addition, the role of eIF5A, containing hypusine formed from spermidine, on protein synthesis is described. These results clearly indicate that polyamines and eIF5A contribute to cell growth and viability through modulation of protein synthesis.

  16. Mammalian polyamine catabolism: a therapeutic target, a pathological problem, or both?

    Science.gov (United States)

    Wang, Yanlin; Casero, Robert A

    2006-01-01

    With the recent discovery of the polyamine catabolic enzyme spermine oxidase (SMO/PAOh1), the apparent complexity of the polyamine metabolic pathway has increased considerably. Alone or in combination with the two other known members of human polyamine catabolism, spermidine/spermine N(1)-acetyltransferase, and N(1)-acetylpolyamine oxidase (PAO), SMO/PAOh1 expression has the potential to alter polyamine homeostasis in response to normal cellular signals, drug treatment and environmental and/or cellular stressors. The activity of the oxidases producing toxic aldehydes and the reactive oxygen species (ROS) H(2)O(2), suggest a mechanism by which these oxidases can be exploited as an antineoplastic drug target. However, inappropriate activation of the pathways may also lead to pathological outcomes, including DNA damage that can lead to cellular transformation. The most recent data suggest that the two polyamine catabolic pathways exhibit distinct properties and understanding these properties should aid in their exploitation for therapeutic and/or chemopreventive strategies.

  17. Interference with polyamine biosynthesis and/or function by analogs of polyamines or methionine as a potential anticancer chemotherapeutic strategy.

    Science.gov (United States)

    Porter, C W; Sufrin, J R

    1986-01-01

    The obvious goal in cancer chemotherapy is selectivity. Highly cytotoxic agents abound but their usefulness as anticancer agents extends only so far as their specificity for tumor cells and tissues. In this context, we have reviewed those aspects of polyamine and AdoMet metabolism and function which might contribute to their potential as target sites for chemotherapeutic intervention. Although largely untested to date and far from unequivocal, these various considerations seem to provide sufficient rationale for continued evaluation of the therapeutic potential of these sites. Polyamine analogs and methionine analogs designed to modulate polyamine biosynthesis directly or through AdoMet formation have been discussed as strategies to effect this goal and previous studies with similar analogs have been reviewed. Progress achieved thus far with analogs derived from our own laboratories provides novel insights into polyamine and AdoMet metabolism and/or function as well as new leads towards the design of more effective agents and drug combinations. More detailed reading of the biochemistry of polyamines in eukaryotes and prokaryotes is available in several very excellent current reviews (6-9, 77).

  18. Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

    Science.gov (United States)

    Zhu, Yu

    Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

  19. Polyamines and cancer; The role of diet polyamines in patients with cancer

    OpenAIRE

    Büyükuslu, Nihal; Erdoğdu Eröz, Seda

    2015-01-01

    Polyamines (putrescine, spermidine and spermine) are basic compounds that are found in all living systems. They are responsible for cell proliferation and differentiation, DNA, RNA and protein synthesis. In addition to the endogenous synthesis of polyamines inside the cell, exogenous intake is also possible. The activity of enzymes that are involved in polyamine synthesis increases in cancer tissues, and consequently the level of polyamines rise. Therefore, polyamine concentrations in serum a...

  20. 40 CFR 721.6186 - Polyamine dithiocarbamate.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyamine dithiocarbamate. 721.6186... Substances § 721.6186 Polyamine dithiocarbamate. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a polyamine dithiocarbamate (PMN No....

  1. Nanoparticle strategies for cancer therapeutics: Nucleic acids, polyamines, bovine serum amine oxidase and iron oxide nanoparticles (Review).

    Science.gov (United States)

    Agostinelli, Enzo; Vianello, Fabio; Magliulo, Giuseppe; Thomas, Thresia; Thomas, T J

    2015-01-01

    Nanotechnology for cancer gene therapy is an emerging field. Nucleic acids, polyamine analogues and cytotoxic products of polyamine oxidation, generated in situ by an enzyme-catalyzed reaction, can be developed for nanotechnology-based cancer therapeutics with reduced systemic toxicity and improved therapeutic efficacy. Nucleic acid-based gene therapy approaches depend on the compaction of DNA/RNA to nanoparticles and polyamine analogues are excellent agents for the condensation of nucleic acids to nanoparticles. Polyamines and amine oxidases are found in higher levels in tumours compared to that of normal tissues. Therefore, the metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, can be targets for antineoplastic therapy since these naturally occurring alkylamines are essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. In particular, polyamine catabolism involves copper-containing amine oxidases. Several studies showed an important role of these enzymes in developmental and disease-related processes in animals through the control of polyamine homeostasis in response to normal cellular signals, drug treatment, and environmental and/or cellular stress. The production of toxic aldehydes and reactive oxygen species (ROS), H2O2 in particular, by these oxidases suggests a mechanism by which amine oxidases can be exploited as antineoplastic drug targets. The combination of bovine serum amine oxidase (BSAO) and polyamines prevents tumour growth, particularly well if the enzyme has been conjugated with a biocompatible hydrogel polymer. The findings described herein suggest that enzymatically formed cytotoxic agents activate stress signal transduction pathways, leading to apoptotic cell death. Consequently, superparamagnetic nanoparticles or other

  2. Hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to gamma radiation and depleted uranium singly and in combination

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: yso@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Evensen, Øystein [Norwegian University of Life Sciences (NMBU), Department of Basic Sciences and Aquatic Medicine, P.O. Box 8146 Dep., N-0033 Oslo (Norway); Lind, Ole Christian [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management (INA), P.O. Box 5003, N-1432 Ås (Norway); and others

    2016-08-15

    Radionuclides are a special group of substances posing both radiological and chemical hazards to organisms. As a preliminary approach to understand the combined effects of radionuclides, exposure studies were designed using gamma radiation (Gamma) and depleted uranium (DU) as stressors, representing a combination of radiological (radiation) and chemical (metal) exposure. Juvenile Atlantic salmon (Salmo salar) were exposed to 70 mGy external Gamma dose delivered over the first 5 h of a 48 h period (14 mGy/h), 0.25 mg/L DU were exposed continuously for 48 h and the combination of the two stressors (Combi). Water and tissue concentrations of U were determined to assess the exposure quality and DU bioaccumulation. Hepatic gene expression changes were determined using microarrays in combination with quantitative real-time reverse transcription polymerase chain reaction (qPCR). Effects at the higher physiological levels were determined as plasma glucose (general stress) and hepatic histological changes. The results show that bioaccumulation of DU was observed after both single DU and the combined exposure. Global transcriptional analysis showed that 3122, 2303 and 3460 differentially expressed genes (DEGs) were significantly regulated by exposure to gamma, DU and Combi, respectively. Among these, 349 genes were commonly regulated by all treatments, while the majority was found to be treatment-specific. Functional analysis of DEGs revealed that the stressors displayed similar mode of action (MoA) across treatments such as induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation, but also stressor-specific mechanisms such as cellular stress and injury, metabolic disorder, programmed cell death, immune response. No changes in plasma glucose level as an indicator of general stress and hepatic histological changes were observed. Although no direct linkage was successfully established between molecular responses and adverse effects at the organism

  3. Immune Depletion in Combination with Allogeneic Islets Permanently Restores Tolerance to Self-Antigens in Diabetic NOD Mice.

    Directory of Open Access Journals (Sweden)

    Nicola Gagliani

    Full Text Available The destruction of beta cells in type 1 diabetes (T1D results in loss of insulin production and glucose homeostasis. Treatment of non-obese diabetic (NOD mice with immune-depleting/modulating agents (e.g., anti-CD3, murine anti-thymocyte-globulin (mATG can lead to diabetes reversal. However, for preclinical studies with these and other agents seeking to reverse disease at onset, the necessity for exogenous insulin administration is debated. Spontaneously diabetic NOD mice were treated with a short-course of mATG and insulin provided as drug therapy or by way of allogeneic islet implants. Herein we demonstrate that exogenous insulin administration is required to achieve disease reversal with mATG in NOD mice. Unexpectedly, we also observed that provision of insulin by way of allogeneic islet implantation in combination with mATG leads to a pronounced reversal of diabetes as well as restoration of tolerance to self-islets. Expansion/induction of regulatory cells was observed in NOD mice stably cured with mATG and allogeneic islets. These data suggest that transient provision of allogeneic insulin-producing islets might provide a temporary window for immune depletion to be more effective and instilling stable tolerance to endogenous beta cells. These findings support the use of a never before explored approach for preserving beta cell function in patients with recent onset T1D.

  4. Dissecting rice polyamine metabolism under controlled long-term drought stress.

    Directory of Open Access Journals (Sweden)

    Phuc Thi Do

    Full Text Available A selection of 21 rice cultivars (Oryza sativa L. ssp. indica and japonica was characterized under moderate long-term drought stress by comprehensive physiological analyses and determination of the contents of polyamines and selected metabolites directly related to polyamine metabolism. To investigate the potential regulation of polyamine biosynthesis at the transcriptional level, the expression of 21 genes encoding enzymes involved in these pathways were analyzed by qRT-PCR. Analysis of the genomic loci revealed that 11 of these genes were located in drought-related QTL regions, in agreement with a proposed role of polyamine metabolism in rice drought tolerance. The cultivars differed widely in their drought tolerance and parameters such as biomass and photosynthetic quantum yield were significantly affected by drought treatment. Under optimal irrigation free putrescine was the predominant polyamine followed by free spermidine and spermine. When exposed to drought putrescine levels decreased markedly and spermine became predominant in all cultivars. There were no correlations between polyamine contents and drought tolerance. GC-MS analysis revealed drought-induced changes of the levels of ornithine/arginine (substrate, substrates of polyamine synthesis, proline, product of a competing pathway and GABA, a potential degradation product. Gene expression analysis indicated that ADC-dependent polyamine biosynthesis responded much more strongly to drought than the ODC-dependent pathway. Nevertheless the fold change in transcript abundance of ODC1 under drought stress was linearly correlated with the drought tolerance of the cultivars. Combining metabolite and gene expression data, we propose a model of the coordinate adjustment of polyamine biosynthesis for the accumulation of spermine under drought conditions.

  5. B-cell dysfunction and depletion using mycophenolate mofetil in a pediatric combined liver and kidney graft recipient.

    Science.gov (United States)

    Ganschow, R; Lyons, M; Kemper, M J; Burdelski, M

    2001-02-01

    The use of mycophenolate mofetil (MMF) in combination with cyclosporin A (CsA) and steroids is well established after kidney transplantation (Tx) in children. A 9-yr-old girl with primary hyperoxaluria type 1 and systemic oxalosis underwent a combined kidney and liver Tx at our institution. The post-operative immunosuppression consisted of CsA, prednisolone, and MMF. Four weeks post-transplant the girl suffered from a severe urinary tract infection caused by Pseudomonas aeruginosa, when the serum immunoglobulin G (IgG) concentration was found to be critically low (IVIG) substitution was necessary. There was no significant loss of immunoglobulins in the ascites and urine and no other medication with possible side-effects on B cells was given. We suggest that MMF can lead to suppressed IgG production by B cells and can cause a defective differentiation into mature B cells. In vitro studies demonstrated these effects of MMF on B cells, but no in vivo cases of this phenomenon have been reported. B-cell counts and serum IgG concentrations returned to normal values after discontinuing the MMF. As we can assume that the observed B-cell dysfunction and depletion were MMF related, we suggest that serum IgG concentrations should be monitored when MMF is used after solid-organ Tx.

  6. Role of polyamines in gastrointestinal mucosal growth

    Institute of Scientific and Technical Information of China (English)

    Zhao Xiang Bian; Jian Hua Wang

    2000-01-01

    The polyamines [putrescine (PU), spermidine (SPD) and spermine (SPM)] are ubiquitous polycationiccompounds found in all prokaryotic and eukaryotic cells, are essentially involved in a variety of regulatorysteps during normal, adaptive, and malignant cell proliferation. Nearly four decades investigation about thepolyamines contributed to the synthesis and decomposition of polyamines and the active and passive enzymeswhich regulate them at different levels. This review focuses on the sources and homeostasis of intracellularpolyamines, the transport and role of the polyamines in the growth of the gastrointestinal mucosa and theirpossible mechanism. We tried to point out the gaps remaining in the story and give a working hypothesis forthe role of polyamines in gastrointestinal mucosal growth. We propose in the hypothesis that polyamine is a“key”to unlock the “door”of cell proliferation. How many “doors” between the “polyamine key” and the“real start” of proliferation? The polyamine might be the only key for cell proliferation. Another possibilityis that polyamine is the first key and its “unlocking-effect” resulting in getting another key for the next doorin the proliferation chain, for example, proto-oncogenes. To decide whether polyamine is an intermediatestep or just only one step of cell proliferation, the possible way is to keep polyamine to be a stimulus and finda way to deprive the function of proto-oncogene protein (or other possible gene expression product) to checkthe effect on the cell proliferation. Another important question is how polyamine can trigger the synthesis ofDNA in virtual. Arabinose operon model may give us some ideas to investigate about that. And furthermore,it is necessary to pay attention to the relationship between polyamine and other cell proliferation regulator,like growth factor, chalone, cAMP, cGMP, etc. Further studies are needed to investigate the mechanism ofpolyamine acted on the gastrointestinal mucosal

  7. Correlation between Polyamines and Growth Regulators

    DEFF Research Database (Denmark)

    Gemici, Meliha; Unal, D.; Azeri, N.;

    2007-01-01

    Compounds of polyamines, considering to be essential for life, are found in prokaryotes and eukaryotes. Although their exact functions have not yet been identified, it is clear that the polyamines play important specific roles in a number of cellular processes such as replication and translation......, embryonic development, cell cycle, programmed cell death and cancer. In addition, the metabolic pathway of these compounds is lighten in recent years, the relationship between polyamines and hormones still remains unclear. In this study, we suggest that cytokinin and auxin, a plant growth hormone...... and regulating cell cycle progression, could be correlated with polyamines....

  8. Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Son, Cheol-Hun [Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Bae, Jae-Ho [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Shin, Dong-Yeok; Lee, Hong-Rae; Jo, Wol-Soon; Yang, Kwangmo [Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Park, You-Soo, E-mail: biotek01@hanmail.net [Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

    2015-06-01

    Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.

  9. Short-term cross-sensitizion of need-free sugar intake by combining sodium depletion and hypertonic NaCl intake.

    Science.gov (United States)

    Santos, Bruna M; de Andrade, Carina A F; Menani, José V; De Luca, Laurival A

    2016-12-01

    History of sodium depletion cross-sensitizes the effects of drugs of abuse. The objective of the present study was to find out if history of sodium depletion also cross-sensitizes a natural reward such as sugar intake in the rat. Sodium depletion was induced by furosemide combined with removal of ambient sodium for 24 h; it was repeated seven days later. The depletion was immediately followed by 0.3 M NaCl intake in a sodium appetite test (active sodium repletion). Seven days after the last depletion, hydrated and fed (need-free) sucrose-naïve animals were offered 10% sucrose in a first 2-h sucrose test. The sucrose test was repeated once a day in a series of five consecutive days. History of sodium depletion enhanced sucrose intake in the first and second tests; it had no effect from the third to fifth sucrose test. The effect on the initial sucrose intake tests disappeared if the rats did not ingest 0.3 M NaCl in the sodium appetite test. Prior experience with sucrose intake in need-free conditions had no effect on sodium appetite. History of intracellular dehydration transiently influenced sucrose intake in the first sucrose test. We found no evidence for thirst sensitization. We conclude that history of dehydration, particularly that resulting from sodium depletion, combined to active sodium repletion, produced short-term cross-sensitization of sucrose intake in sucrose-naïve rats. The results suggest that the cross-sensitization of sucrose intake related with acquisition of sugar as a novel nutrient rather than production of lasting effects on sugar rewarding properties.

  10. Significance of targeting polyamine metabolism as an antineoplastic strategy: unique targets for polyamine analogues.

    Science.gov (United States)

    Casero, Robert A; Frydman, Benjamin; Stewart, Tracy Murray; Woster, Patrick M

    2005-01-01

    The polyamines, putrescine, spermidine, and spermine, are naturally occurring polycationic alkylamines that are absolutely required for eukaryotic cell growth. Importantly, the polyamine metabolic pathway, as well as the requirement of polyamines for cell growth, is frequently dysregulated in cancer cells, thus providing a unique set of targets for therapeutic intervention. Ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis, is frequently up-regulated in preneoplastic cells, and has been implicated as an oncogene in multiple tumor types. Several model systems have demonstrated that inhibition of ODC's enzymatic activity and down-regulation of its expression are rational strategies for both chemotherapy and chemoprevention. Specific inhibitors of ODC, most notably 2-difluoromethylornithine (DFMO), have been used experimentally to validate polyamine metabolism as an antineoplastic strategy. However, multiple biochemical and clinical limitations to these ODC-targeting strategies minimize their value as therapeutic tools. Included among these limitations are poor bioavailability of the inhibitor, and the compensatory up-regulation of polyamine metabolism and transport that allow tumor cells to escape the growth inhibitory effects of blockers specifically targeting ODC. As a strategy to overcome the limitations of direct enzyme inhibition, several groups have pursued the design of polyamine analogues that specifically target the dysregulated polyamine metabolism found in tumors. These analogues have been developed specifically to target the specific polyamine transporter, thus competing with circulating natural polyamines. Additionally, most of the analogues examined thus far maintain the regulatory function of the natural polyamines, but are unable to functionally substitute for them in promoting growth. Specifically, individual analogues have demonstrated the ability to down-regulate each of the biosynthetic enzymes without causing

  11. YB-1 immunization combined with regulatory T-cell depletion induces specific T-cell responses that protect against neuroblastoma in the early stage

    Institute of Scientific and Technical Information of China (English)

    Jin Zheng; Ping Liu; Xiaofeng Yang

    2012-01-01

    Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy.Currently,no effective clinical treatments are available for advanced neuroblastoma.In a previous study,we screened Y Box protein 1 (YB-1) as a potential neuroblastoma-associated antigen from sera of AGN2a-immunized mice by serological analysis of recombinant cDNA expression libraries technique.The aim of this study is to explore if YB-1 immunization in the context of Treg depletion could induce protective immune response against the neuroblastoma in mice.YB-1 was expressed and purified by pET-15b prokaryotic expression system.It was demonstrated that anti-YB-1 CD8+ T-cell responses could be induced by AGN2a immunization,and the strongest CD8+ T-cell responses against AGN2a were induced by YB-1-immunized mice in the context of Treg depletion compared with YB-1 only immunization group and control group.Importantly,the survival rate of mice treated with YB-1 immunization combined with Treg depletion was 80% when challenged by 1 × 104 AGN2a cells,significantly higher than that of mice immunized with YB-1 alone (P< 0.01).Furthermore,T-cell adoptive therapy showed that the neuroblastoma growth was inhibited when T cells or splenic cells from YB-1-immunized mice with Treg depletion were transferred to AGN2a bearing mice.Both CD4+ and CD8+ T cells were involved in the anti-neuroblastoma responses induced by YB-1immunization combined with Treg depletion.These results indicated that YB-1 immunization combined with Treg depletion could induce specific T-cell responses against neuroblastoma and could be a potential strategy for the prevention and treatment of neuroblastoma in the early stage.

  12. Polyamine metabolic canalization in response to drought stress in Arabidopsis and the resurrection plant Craterostigma plantagineum

    Science.gov (United States)

    Bartels, Dorothea; Koncz, Csaba; Altabella, Teresa

    2011-01-01

    In this work, we have studied the transcriptional profiles of polyamine biosynthetic genes and analyzed polyamine metabolic fluxes during a gradual drought acclimation response in Arabidopsis thaliana and the resurrection plant Craterostigma plantagineum. The analysis of free putrescine, spermidine and spermine titers in Arabidopsis arginine decarboxylase (adc1–3, adc2–3), spermidine synthase (spds1–2, spds2–3) and spermine synthase (spms-2) mutants during drought stress, combined with the quantitative expression of the entire polyamine biosynthetic pathway in the wild-type, has revealed a strong metabolic canalization of putrescine to spermine induced by drought. Such canalization requires spermidine synthase 1 (SPDS1) and spermine synthase (SPMS) activities and, intriguingly, does not lead to spermine accumulation but to a progressive reduction in spermidine and spermine pools in the wild-type. Our results suggest the participation of the polyamine back-conversion pathway during the drought stress response rather than the terminal catabolism of spermine. The putrescine to spermine canalization coupled to the spermine to putrescine back-conversion confers an effective polyamine recycling-loop during drought acclimation. Putrescine to spermine canalization has also been revealed in the desiccation tolerant plant C. plantagineum, which conversely to Arabidopsis, accumulates high spermine levels which associate with drought tolerance. Our results provide a new insight to the polyamine homeostasis mechanisms during drought stress acclimation in Arabidopsis and resurrection plants. PMID:21330782

  13. Regulated expression of an essential allosteric activator of polyamine biosynthesis in African trypanosomes.

    Directory of Open Access Journals (Sweden)

    Erin K Willert

    2008-10-01

    Full Text Available Trypanosoma brucei is the causative agent of African sleeping sickness. The polyamine biosynthetic pathway has the distinction of being the target of the only clinically proven anti-trypanosomal drug with a known mechanism of action. Polyamines are essential for cell growth, and their metabolism is extensively regulated. However, trypanosomatids appear to lack the regulatory control mechanisms described in other eukaryotic cells. In T. brucei, S-adenosylmethionine decarboxylase (AdoMetDC and ornithine decarboxylase (ODC are required for the synthesis of polyamines and also for the unique redox-cofactor trypanothione. Further, trypanosomatid AdoMetDC is activated by heterodimer formation with a catalytically dead homolog termed prozyme, found only in these species. To study polyamine regulation in T. brucei, we generated inducible AdoMetDC RNAi and prozyme conditional knockouts in the mammalian blood form stage. Depletion of either protein led to a reduction in spermidine and trypanothione and to parasite death, demonstrating that prozyme activation of AdoMetDC is essential. Under typical growth conditions, prozyme concentration is limiting in comparison to AdoMetDC. However, both prozyme and ODC protein levels were significantly increased relative to stable transcript levels by knockdown of AdoMetDC or its chemical inhibition. Changes in protein stability do not appear to account for the increased steady-state protein levels, as both enzymes are stable in the presence of cycloheximide. These observations suggest that prozyme and ODC are translationally regulated in response to perturbations in the pathway. In conclusion, we describe the first evidence for regulation of polyamine biosynthesis in T. brucei and we demonstrate that the unique regulatory subunit of AdoMetDC is a key component of this regulation. The data support ODC and AdoMetDC as the key control points in the pathway and the likely rate-limiting steps in polyamine biosynthesis.

  14. Current status of the polyamine research field.

    Science.gov (United States)

    Pegg, Anthony E; Casero, Robert A

    2011-01-01

    This chapter provides an overview of the polyamine field and introduces the 32 other chapters that make up this volume. These chapters provide a wide range of methods, advice, and background relevant to studies of the function of polyamines, the regulation of their content, their role in disease, and the therapeutic potential of drugs targeting polyamine content and function. The methodology provided in this new volume will enable laboratories already working in this area to expand their experimental techniques and facilitate the entry of additional workers into this rapidly expanding field.

  15. Polyamines and cancer: implications for chemotherapy and chemoprevention.

    Science.gov (United States)

    Nowotarski, Shannon L; Woster, Patrick M; Casero, Robert A

    2013-02-22

    Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.

  16. Polyamines and cancer: Implications for chemoprevention and chemotherapy

    Science.gov (United States)

    Nowotarski, Shannon L.; Woster, Patrick M.; Casero, Robert A.

    2013-01-01

    Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes and a poorly characterized transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate, and skin cancers, and altered levels of the rate limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway specific drugs, and ongoing clinical trials targeting polyamine biosynthesis. PMID:23432971

  17. Stress and Polyamine Metabolism in Fungi

    Science.gov (United States)

    Valdés-Santiago, Laura; Ruiz-Herrera, José

    2013-12-01

    Fungi, as well as the rest of living organisms must deal with environmental challenges such as stressful stimuli. Fungi are excellent models to study the general mechanisms of the response to stress, because of their simple, but conserved, signal-transduction and metabolic pathways that are often equivalent to those present in other eukaryotic systems. A factor that has been demonstrated to be involved in these responses is polyamine metabolism, essentially of the three most common polyamines: putrescine, spermidine and spermine. The gathered evidences on this subject suggest that polyamines are able to control cellular signal transduction, as well as to modulate protein-protein interactions. In the present review, we will address the recent advances on the study of fungal metabolism of polyamines, ranging from mutant characterization to potential mechanism of action during different kinds of stress in selected fungal models.

  18. STRESS AND POLYAMINE METABOLISM IN FUNGI

    Directory of Open Access Journals (Sweden)

    Laura eValdés-Santiago

    2014-01-01

    Full Text Available Fungi, as well as the rest of living organisms must deal with environmental challenges such as stressful stimuli. Fungi are excellent models to study the general mechanisms of the response to stress, because of their simple, but conserved, signal-transduction and metabolic pathways that are often equivalent to those present in other eukaryotic systems. A factor that has been demonstrated to be involved in these responses is polyamine metabolism, essentially of the three most common polyamines: putrescine, spermidine and spermine. The gathered evidences on this subject suggest that polyamines are able to control cellular signal transduction, as well as to modulate protein-protein interactions. In the present review, we will address the recent advances on the study of fungal metabolism of polyamines, ranging from mutant characterization to potential mechanism of action during different kinds of stress in selected fungal models.

  19. Stress and polyamine metabolism in fungi.

    Science.gov (United States)

    Valdés-Santiago, Laura; Ruiz-Herrera, José

    2013-01-01

    Fungi, as well as the rest of living organisms must deal with environmental challenges such as stressful stimuli. Fungi are excellent models to study the general mechanisms of the response to stress, because of their simple, but conserved, signal-transduction and metabolic pathways that are often equivalent to those present in other eukaryotic systems. A factor that has been demonstrated to be involved in these responses is polyamine metabolism, essentially of the three most common polyamines: putrescine, spermidine and spermine. The gathered evidences on this subject suggest that polyamines are able to control cellular signal transduction, as well as to modulate protein-protein interactions. In the present review, we will address the recent advances on the study of fungal metabolism of polyamines, ranging from mutant characterization to potential mechanism of action during different kinds of stress in selected fungal models.

  20. Oligoamine analogues in combination with 2-difluoromethylornithine synergistically induce re-expression of aberrantly silenced tumour-suppressor genes.

    Science.gov (United States)

    Wu, Yu; Steinbergs, Nora; Murray-Stewart, Tracy; Marton, Laurence J; Casero, Robert A

    2012-03-15

    Epigenetic gene silencing is an important mechanism in the initiation and progression of cancer. Abnormal DNA CpG island hypermethylation and histone modifications are involved in aberrant silencing of tumour-suppressor genes. LSD1 (lysine-specific demethylase 1) was the first enzyme identified to specifically demethylate H3K4 (Lys(4) of histone H3). Methylated H3K4 is an important mark associated with transcriptional activation. The flavin adenine dinucleotide-binding amine oxidase domain of LSD1 is homologous with two polyamine oxidases, SMO (spermine oxidase) and APAO (N(1)-acetylpolyamine oxidase). We have demonstrated previously that long-chain polyamine analogues, the oligoamines, are inhibitors of LSD1. In the present paper we report the synergistic effects of specific oligoamines in combination with DFMO (2-difluoromethylornithine), an inhibitor of ornithine decarboxylase, in human colorectal cancer cells. DFMO treatment depletes natural polyamines and increases the uptake of exogenous polyamines. The combination of oligoamines and DFMO results in a synergistic re-expression of aberrantly silenced tumour-suppressor genes, including SFRP2 (secreted frizzled-related protein 2), which encodes a Wnt signalling pathway antagonist and plays an anti-tumorigenic role in colorectal cancer. The treatment-induced re-expression of SFRP2 is associated with increased H3K4me2 (di-methyl H3K4) in the gene promoter. The combination of LSD1-inhibiting oligoamines and DFMO represents a novel approach to epigenetic therapy of cancer.

  1. Biochemical and morphological effects of polyamine biosynthesis inhibitors on Trichophyton and Microsporum.

    Science.gov (United States)

    Gruhn, C M; Boyle, S M

    1991-01-01

    The minimum inhibitory concentrations (MICs) of three known irreversible inhibitors of polyamine synthesis, alpha-difluoromethylornithine (DFMO) and monofluoromethyldehydroornithine methylester (MFMOme), inhibitors of ornithine decarboxylase (ODC) and alpha-difluoromethylarginine (DFMA), an inhibitor of arginine decarboxylase (ADC), were determined for 10 species of dermatophytic fungi. Trichophyton species were generally more sensitive to these inhibitors than Microsporum species. Both genera produced arginase, and treatment of members of either genus with DFMO or DFMA resulted in an inhibition of ODC activity and a depletion of cellular polyamines. However, conversion of labelled DFMA to DFMO, either in vivo or in vitro, could not be demonstrated in spite of both genera producing arginase. The ultrastructure of cells cultured in the presence of either DFMO or DFMA was similar, and revealed disruption of calcium metabolism, an increase in mitochondrial number and alterations to membrane systems. DFMA and DFMO also inhibited sporulation in Microsporum gypseum. Our findings indicate that DFMO limits the growth of dermatophytes by direct inhibition of ODC and lowering of cellular polyamine levels; in contrast, DFMA inhibits polyamine synthesis in an unspecified manner as ADC activity was undetected.

  2. Transcriptional effects of polyamines on ribosomal proteins and on polyamine-synthesizing enzymes in Escherichia coli.

    Science.gov (United States)

    Huang, S C; Panagiotidis, C A; Canellakis, E S

    1990-05-01

    We find that the transcription of various ribosomal proteins can be differentially affected by polyamines and by changes in growth rates. Using strain MG1655 of Escherichia coli K-12 (F-, lambda-), we have determined the effects of polyamines and changes in growth rate on the transcription of several ribosomal genes and the polyamine-synthesizing enzymes ornithine decarboxylase (L-ornithine carboxy-lyase; EC 4.1.1.17) and arginine decarboxylase (L-arginine carboxylyase; EC 4.1.1.19). Ribosomal proteins S20 and L34 can be differentiated from the other ribosomal proteins studied; the transcription of S20 and L34 is especially sensitive to polyamines and less sensitive to changes in growth rates. In contrast, the transcription of S10, S15, S19, L2, L4, L20, L22, and L23 is insensitive to polyamines although it is particularly sensitive to changes in growth rates. Like S20 and L34, the transcription of ornithine decarboxylase and arginine decarboxylase is especially sensitive to polyamines. Polyamines specifically enhance the transcription of ribosomal proteins S20 and L34, and decrease that of ornithine decarboxylase and arginine decarboxylase. It is evident that polyamines can exert both positive and negative regulation of gene expression in E. coli that can be differentiated from the effects caused by changes in growth rates.

  3. In vitro effects of extract of Senna alata (Ceasalpiniaceae on the polyamines produced by Leukaemia cells (L1210

    Directory of Open Access Journals (Sweden)

    C A Pieme

    2009-01-01

    Full Text Available The present study reports the effects of S. alata (Ceasalpiniaceae extract on the metabolism of polyamines resulting from the proliferation of leukaemia cells (L1210. The results established that the inhibition of cell proliferation was significantly increased with the concentration of extract from 28 to 32.80 % after 72 h. The percentage of cells viability changed significantly from 9.72 to 80 % when cells are treated with extract alone, in combination with DEMO or putrescine. The levels of the intracellular yield of putrescine, spermidine and spermine were also reduced by the extract compared to the control. The DEMO-extract complex enhanced the inhibition of the production polyamines up to 95 %. In opposite, the complex S. alata- putrescine complex stimulated significantly its biosynthesis of polyamines. A significant reduction of the level of protein after 72 h of treatment was observed. This result corroborated with the reduction of polyamines resulting from inhibition cell proliferation.

  4. Changes of polyamine pattern in digestive glands of mussel Mytilus galloprovincialis under exposure to cadmium.

    Science.gov (United States)

    Kournoutou, Georgia G; Pytharopoulou, Sofia; Leotsinidis, Michel; Kalpaxis, Dimitrios L

    2014-09-01

    Polyamines, in particular spermidine and spermine, have been identified as important antioxidants, highly induced by oxidative stress in a variety of organisms. However, little is known about changes in polyamine content of metal-stressed marine organisms. In the present study, mussels (Mytilus galloprovincialis) were experimentally exposed to 25 μg/L Cd(2+) or 100 μg/L Cd(2+) for up to 15 days. Cd(2+) was progressively accumulated in mussel tissues, leading to a characteristic oxidative-stress status. Free putrescine (PUT) production was noticeably induced in response to Cd(2+) at day 5 and then declined. In contrast, free spermidine (SPD) content was gradually reduced, whereas the concentration of free spermine (SPM) increased. In combination, these changes led to a 69% or 88% reduction in the ratio of (SPD+SPM)/PUT at day 5, dependent on the Cd(2+) concentration used, which subsequently followed an upward trend in values, albeit not reaching those of controls. Conjugated polyamines constantly increased, in particular conjugated spermidine and spermine, tagging along with metallothionein production. Acetylated polyamines showed a diverse profile of changes, but their content was generally kept at low levels throughout the exposure period. Collectively, our results suggest that certain polyamine compounds could play a significant role in the tolerance of mussels against Cd(2+)-mediated stress, and that the ratio (SPD+SPM)/PUT could be a good indicator of the metal-stress status.

  5. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ghanashyam Sarikonda

    Full Text Available A recent type 1 diabetes (T1D clinical trial of rituximab (a B cell-depleting anti-CD20 antibody achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin with anti-CD3 antibody (a T cell-directed immunomodulator offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks was also ineffective, while proinsulin DNA (weekly for up to 12 weeks showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04. In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.

  6. Recent advances in the medicinal chemistry of polyamine toxins

    DEFF Research Database (Denmark)

    Strømgaard, K; Andersen, K; Krogsgaard-Larsen, P

    2001-01-01

    This review describes the recent developments in the field of polyamine toxins, with focus on structure activity relationship investigations, including studies of importance of the polyamine moiety for biological activity, photolabeling studies using polyamine toxins as templates, as well as use ...

  7. Localization and biosynthesis of polyamines in insulin-producing cells

    DEFF Research Database (Denmark)

    Hougaard, D M; Larsson, L I; Nielsen, Jens Høiriis

    1986-01-01

    Two recently developed fluorescence cytochemical methods, specific for spermidine and spermine, were used to localize polyamines in the endocrine pancreas. The polyamines were restricted to the insulin-producing beta-cells and were mainly associated with the secretory granules. Chemical polyamine...

  8. Speculation: Polyamines are important in abiotic stress signaling.

    Science.gov (United States)

    Pál, Magda; Szalai, Gabriella; Janda, Tibor

    2015-08-01

    The main role of polyamines was originally assumed to be as direct protective compounds important under stress conditions. Although in some cases a correlation was found between the endogenous polyamine content and stress tolerance, this relationship cannot be generalized. Polyamines should no longer be considered simply as protective molecules, but rather as compounds that are involved in a complex signaling system and have a key role in the regulation of stress tolerance. The major links in polyamine signaling may be H2O2 and NO, which are not only produced in the course of the polyamine metabolism, but also transmit signals that influence gene expression via an increase in the cytoplasmic Ca(2+) level. Polyamines can also influence Ca(2+) influx independently of the H2O2- and/or NO-mediated pathways. Furthermore, these pathways may converge. In addition, several protein kinases have been shown to be influenced at the transcriptional or post-translational level by polyamines. Individual polyamines can be converted into each other in the polyamine cycle. In addition, their metabolism is linked with other hormones or signaling molecules. However, as individual polyamines trigger different transcriptional responses, other mechanisms and the existence of polyamine-responsive elements and the corresponding transacting protein factors are also involved in polyamine-related signaling pathways.

  9. Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2014-01-01

    Full Text Available Exposure to ionizing radiation alone (radiation injury, RI or combined with traumatic tissue injury (radiation combined injury, CI is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to 60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.

  10. Possible role of polyamines in gyrate atrophy.

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    Sulochana Konerirajapuram

    2000-01-01

    Full Text Available PURPOSE: Gyrate atrophy (GA is marked by hyperornithinemia and lowered ornithine amino transferase (OAT. However there are patients of GA without hyperornithinemia and those with hyperornithinemia without GA. Some cases of GA have been reported to have low lysine. The purpose of the study was to determine if polyamines, the metabolites of ornithine, and lysine have any diagnostic role in GA. METHODS: Ornithine in plasma was estimated by two-dimensional paper chromatography, with elution of the coloured spot, and the absorbance measured using a spectrophotometer at 560 nm. OAT assay in lymphocytes was done spectrophotometrically using ornithine as substrate. Blood and urinary polyamines were extracted with n-butanol, benzoylated and analysed with HPLC; putrescine, spermine, spermidine, and cadaverine were assayed individually at 254 nm with the UV detector using ODS, G18 column with 63% methanol as solvent. RESULTS: Of the 7 patients investigated, 6 had features typical of GA. One was diagnosed to have atypical retinitis pigmentosa (case 3. The first five cases had elevated ornithine and diminished OAT, but cases 6 and 7 had near-normal ornithine and case 7 had near-normal OAT. However, all 7 patients had increased levels of total polyamines in urine compared to normals. Five had increased putrescine and three had increased spermine. All the 7 had decreased cadaverine in urine. Thus, though there were inconsistencies with ornithine and OAT, all the 7 patients had elevated polyamines from ornithine and decreased cadaverine. CONCLUSION: In addition to estimating ornithine and OAT in GA, it is suggested that urinary polyamines may be analysed as the latter appears to correlate better with the clinical condition and help in the diagnosis to a greater extent. Moreover, while ornithine is an innocuous amino acid, polyamines are known to damage DNA and proteins.

  11. Polyamines Function in Stress Tolerance: From Synthesis to Regulation

    Directory of Open Access Journals (Sweden)

    Ji-Hong eLiu

    2015-10-01

    Full Text Available Plants are challenged by a variety of biotic or abiotic stresses, which can affect their growth and development, productivity and geographic distribution. In order to survive adverse environmental conditions, plants have evolved various adaptive strategies, among which is the accumulation of metabolites that play protective roles. A well-established example of the metabolites that are involved in stress responses, or stress tolerance, is the low-molecular-weight aliphatic polyamines, including putrescine,spermidine and spermine. The critical role of polyamines in stress tolerance is suggested by several lines of evidence: firstly, the transcript levels of polyamine biosynthetic genes, as well as the activities of the corresponding enzymes, are induced by stresses; secondly, elevation of endogenous polyamine levels by exogenous supply of polyamines, or overexpression of polyamine biosynthetic genes, results in enhanced stress tolerance; and thirdly, a reduction of endogenous polyamines is accompanied by compromised stress tolerance. A number of studies have demonstrated that polyamines function in stress tolerance largely by modulating the homeostasis of reactive oxygen species (ROS due to their direct, or indirect, roles in regulating antioxidant systems or suppressing ROS production. The transcriptional regulation of polyamine synthesis by transcription factors is also reviewed here. Meanwhile, future perspectives on polyamine research are also suggested.

  12. Determination of substrate specificity of polyamine transporters in roseobacter species

    Science.gov (United States)

    Madhuri, S.; Mou, X.

    2012-12-01

    Polyamines, such as cadaverine, putrescine, spermidine, spermine and norspermine are a class of dissolved organic nitrogen (DON) that is ubiquitously found in marine environments. Intracellular polyamines are important in a variety of biological reactions, such as nucleic acid synthesis and protein synthesis. Free polyamines in seawater can be transported into bacterial cells by ABC transporter systems, each of which consists of four components including one substrate binding protein, one ATPase and two permeases. In silico analysis of marine bacterial genomes has revealed that roseobacter, a numerically and ecologically important taxa of marine bacteria, have at least two sets of polyamine transporter genes. This study was to examine the potential preference of roseobacter to different polyamine compounds and the substrate specificity of different polyamine transporters. Eleven roseobacter species, which genomes have been sequenced, were grown in defined media supplied with single polyamine compound as the sole carbon and nitrogen source. Growth assay showed a small number of roseobacter isolates to be generalist showing no preference among the tested polyamines (Ruegeria pomeroyi DSS-3, Roseovarius sp. TM1035, Roseovarius nubinhibens ISM, Jannaschia sp. CCS1 and Sagittula stellata E-37), whereas other isolates were specilists and were specific on polyamine compounds (Roseobacter sp. CCS2 and Roseobacter denitrificans OCh 114). Primers that probe poly-1 and pot-D genes, the two genes that encode common polyamine-binding genes of polyamine transporter systems were designed using net primer and primer design program. The specificity of the primers was validated by PCR followed by amplicon sequencing. Single step reverse transcription quantitative polymerase chain reactions (RT-qPCR) was performed to investigate substrate specificity of poly-1 and pot-D genes. Key-words Roseobacter, polyamine, polyamine transporter, dissolved organic nitrogen

  13. Polyamine-DNA interactions and development of gene delivery vehicles.

    Science.gov (United States)

    Thomas, T J; Tajmir-Riahi, H A; Thomas, Thresia

    2016-10-01

    Polyamines are positively charged organic cations under physiologic ionic and pH conditions and hence they interact with negatively charged macromolecules such as DNA and RNA. Although electrostatic interaction is the predominant mode of polyamine-nucleic acid interactions, site- and structure-specific binding has also been recognized. A major consequence of polyamine-DNA interaction is the collapse of DNA to nanoparticles of approximately 100 nm diameter. Electron and atomic force microscopic studies have shown that these nanoparticles are spheroids, toroids and rods. DNA transport to cells for gene therapy applications requires the condensation of DNA to nanoparticles and hence the study of polyamines and related compounds with nucleic acids has received technological importance. In addition to natural and synthetic polyamines, several amine-terminated or polyamine-substituted agents are under intense investigation for non-viral gene delivery vehicles.

  14. A Drosophila model to identify polyamine-drug conjugates that target the polyamine transporter in an intact epithelium.

    Science.gov (United States)

    Tsen, Chung; Iltis, Mark; Kaur, Navneet; Bayer, Cynthia; Delcros, Jean-Guy; von Kalm, Laurence; Phanstiel, Otto

    2008-01-24

    Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polyamine conjugates for their PAT-selective targeting ability. We report here a novel Drosophila-based model for screening anthracene-polyamine conjugates in a developing and intact epithelium ( Drosophila imaginal discs), wherein cell-cell adhesion properties are maintained. Data from the Drosophila assay are consistent with previous results in CHO cells, indicating that the Drosophila epithelium has a PAT with vertebrate-like characteristics. This assay will be of use to medicinal chemists interested in screening drugs that use PAT for cellular entry, and it offers the possibility of genetic dissection of the polyamine transport process, including identification of a Drosophila PAT.

  15. Effect of polyamines on shoot multiplication and furanocoumarin production in Ruta graveolens cultures.

    Science.gov (United States)

    Diwan, Renuka; Malpathak, Nutan

    2012-07-01

    The influence of the polyamines putrescine (Put), spermine (Spr) and spermidine (Spd) on growth and furanocoumarin production was investigated by exogenous addition, at different concentrations, to shoot cultures of Ruta graveolens at different phases of growth. Preliminary studies indicated that addition of Put (20 microM) and Spr (80 microM) had a promotive effect on shoot multiplication rate and number of multiple shoots formed. Spd was toxic, even at lower concentrations. The growth-phase of the culture at the time of exogenous addition of polyamines was found to be an important factor. Put was most effective when added at the lag phase, while Spr was most effective when added in the log phase. Time course studies of growth and furanocoumarin content were carried out for each polyamine and phase of addition. It was seen that maximum production of furanocoumarins (256.8 mg/10 g DW) occurred in the second week when Put was added in the lag phase and 260.5 mg/10 g DW in the fourth week when Spr was added in the log phase. Put addition resulted in a 3.10 fold increase in psoralen, 6.12 in xanthotoxin and 1.46 fold in bergapten production. Spr addition resulted in a 1.31 fold increase in psoralen, 4.11 fold in xanthotoxin and 1.49 fold in bergapten production. Results indicate that alteration of growth and furanocoumarin production kinetics is a combined outcome of choice of polyamine and the phase of culture at the time of exogenous addition. Polyamine addition enabled significant enhancement in production of pharmaceutically important bergapten and xanthotoxin in shoot cultures of Ruta graveolens, which could be explored for commercial production.

  16. Trypanocidal Effect of Isotretinoin through the Inhibition of Polyamine and Amino Acid Transporters in Trypanosoma cruzi

    Science.gov (United States)

    Reigada, Chantal; Valera-Vera, Edward A.; Sayé, Melisa; Errasti, Andrea E.; Avila, Carla C.; Miranda, Mariana R.; Pereira, Claudio A.

    2017-01-01

    Polyamines are essential compounds to all living organisms and in the specific case of Trypanosoma cruzi, the causative agent of Chagas disease, they are exclusively obtained through transport processes since this parasite is auxotrophic for polyamines. Previous works reported that retinol acetate inhibits Leishmania growth and decreases its intracellular polyamine concentration. The present work describes a combined strategy of drug repositioning by virtual screening followed by in vitro assays to find drugs able to inhibit TcPAT12, the only polyamine transporter described in T. cruzi. After a screening of 3000 FDA-approved drugs, 7 retinoids with medical use were retrieved and used for molecular docking assays with TcPAT12. From the docked molecules, isotretinoin, a well-known drug used for acne treatment, showed the best interaction score with TcPAT12 and was selected for further in vitro studies. Isotretinoin inhibited the polyamine transport, as well as other amino acid transporters from the same protein family (TcAAAP), with calculated IC50 values in the range of 4.6–10.3 μM. It also showed a strong inhibition of trypomastigote burst from infected cells, with calculated IC50 of 130 nM (SI = 920) being significantly less effective on the epimastigote stage (IC50 = 30.6 μM). The effect of isotretinoin on the parasites plasma membrane permeability and on mammalian cell viability was tested, and no change was observed. Autophagosomes and apoptotic bodies were detected as part of the mechanisms of isotretinoin-induced death indicating that the inhibition of transporters by isotretinoin causes nutrient starvation that triggers autophagic and apoptotic processes. In conclusion, isotretinoin is a promising trypanocidal drug since it is a multi-target inhibitor of essential metabolites transporters, in addition to being an FDA-approved drug largely used in humans, which could reduce significantly the requirements for its possible application in the treatment of

  17. Polyamines and α-Carbonic Anhydrases

    Directory of Open Access Journals (Sweden)

    Andrea Scozzafava

    2016-12-01

    Full Text Available Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the inhibition of the metalloenzymes carbonic anhydrases (CAs; EC 4.2.2.1. CA enzymes are established pharmacological targets for important pathologies, which, among others, include glaucoma, hypoxic tumors, and central nervous system (CNS-affecting diseases. Moreover, they are expressed in many bacteria, fungi and helminths which are the etiological agents of the majority of infectious diseases. In this context, natural products represent the ideal source of new and selective druggable CA modulators for biomedical purposes. Herein we report the state of the art on polyamines of natural origin as well as of synthetic derivatives as inhibitors of human CAs.

  18. Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

    Directory of Open Access Journals (Sweden)

    Daniel Fürniss

    2013-01-01

    Full Text Available Sugar moieties are present in a wide range of bioactive molecules. Thus, having versatile and fast methods for the decoration of biomimetic molecules with sugars is of fundamental importance. The glycosylation of peptoids and polyamines as examples of such biomimetic molecules is reported here. The method uses Cu-catalyzed azide alkyne cycloaddition to promote the reaction of azidosugars with either polyamines or peptoids. In addition, functionalized nucleic acids were attached to polyamines via the same route. Based on a modular solid-phase synthesis of peralkynylated peptoids with up to six alkyne groups, the latter were modified with azidosugar building blocks by using copper-catalyzed azide alkyne cycloadditions. In addition, the up-scaling of some particular azide-modified sugars is described.

  19. COMBINED CO AND DUST SCALING RELATIONS OF DEPLETION TIME AND MOLECULAR GAS FRACTIONS WITH COSMIC TIME, SPECIFIC STAR-FORMATION RATE, AND STELLAR MASS

    Energy Technology Data Exchange (ETDEWEB)

    Genzel, R.; Tacconi, L. J.; Lutz, D.; Berta, S.; Burkert, A. [Max-Planck-Institut für Extraterrestrische Physik (MPE), Giessenbachstr., D-85748 Garching (Germany); Saintonge, A. [Department of Physics and Astronomy, University College London, Gower Place, London WC1E 6BT (United Kingdom); Magnelli, B. [Argelander-Institut für Astronomie, Universität Bonn, Auf dem Hügel 71, D-53121 Bonn (Germany); Combes, F. [Observatoire de Paris, LERMA, CNRS, 61 Av. de l' Observatoire, F-75014 Paris (France); García-Burillo, S. [Observatorio Astronómico Nacional-OAN, Observatorio de Madrid, Alfonso XII, 3, 28014 Madrid (Spain); Neri, R.; Boissier, J. [IRAM, 300 Rue de la Piscine, F-38406 St. Martin d' Heres, Grenoble (France); Bolatto, A. [Department of Astronomy, University of Maryland, College Park, MD 20742-2421 (United States); Contini, T.; Boone, F.; Bouché, N. [Institut d' Astrophysique et de Planétologie, Universite de Toulouse, 9 Avenue du Colonel Roche BP 44346, F-31028 Toulouse Cedex 4 (France); Lilly, S.; Carollo, M. [Institute of Astronomy, Department of Physics, Eidgenössische Technische Hochschule, CH-8093 ETH Zürich (Switzerland); Bournaud, F. [Service d' Astrophysique, DAPNIA, CEA/Saclay, F-91191 Gif-sur-Yvette Cedex (France); Colina, L. [CSIC Instituto Estructura Materia, C/Serrano 121, E-28006 Madrid (Spain); Cooper, M. C., E-mail: linda@mpe.mpg.de, E-mail: genzel@mpe.mpg.de [Department of Physics and Astronomy, Frederick Reines Hall, University of California, Irvine, CA 92697 (United States); and others

    2015-02-10

    We combine molecular gas masses inferred from CO emission in 500 star-forming galaxies (SFGs) between z = 0 and 3, from the IRAM-COLDGASS, PHIBSS1/2, and other surveys, with gas masses derived from Herschel far-IR dust measurements in 512 galaxy stacks over the same stellar mass/redshift range. We constrain the scaling relations of molecular gas depletion timescale (t {sub depl}) and gas to stellar mass ratio (M {sub mol} {sub gas}/M{sub *} ) of SFGs near the star formation ''main-sequence'' with redshift, specific star-formation rate (sSFR), and stellar mass (M{sub *} ). The CO- and dust-based scaling relations agree remarkably well. This suggests that the CO → H{sub 2} mass conversion factor varies little within ±0.6 dex of the main sequence (sSFR(ms, z, M {sub *})), and less than 0.3 dex throughout this redshift range. This study builds on and strengthens the results of earlier work. We find that t {sub depl} scales as (1 + z){sup –0.3} × (sSFR/sSFR(ms, z, M {sub *})){sup –0.5}, with little dependence on M {sub *}. The resulting steep redshift dependence of M {sub mol} {sub gas}/M {sub *} ≈ (1 + z){sup 3} mirrors that of the sSFR and probably reflects the gas supply rate. The decreasing gas fractions at high M{sub *} are driven by the flattening of the SFR-M {sub *} relation. Throughout the probed redshift range a combination of an increasing gas fraction and a decreasing depletion timescale causes a larger sSFR at constant M {sub *}. As a result, galaxy integrated samples of the M {sub mol} {sub gas}-SFR rate relation exhibit a super-linear slope, which increases with the range of sSFR. With these new relations it is now possible to determine M {sub mol} {sub gas} with an accuracy of ±0.1 dex in relative terms, and ±0.2 dex including systematic uncertainties.

  20. THE EFFECT OF SPRUCE BARK POLYPHENOLS EXTRACT IN COMBINATION WITH DEUTERIUM DEPLETED WATER (DDW ON GLYCINE MAX L. AND HELIANTHUS ANNUUS L. DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Corneliu Tanase

    2010-09-01

    Full Text Available The aim of this study was to evaluate the effect of spruce bark aqueous extract and deuterium depleted water (DDW as bioregulators on the plant growth Glycine max L. and Helianthus annuus. The following specific parameteres were closely monitorised: germination energy and germination capacity, plants vegetative organelles growth and development and photoassimilatory pigments concentrations. The results have shown that DDW presents different effects depending on tested plant species. In the case of soybean, DDW presented stimulatory effects on both germination energy and capacity, radicles elongation, primary leaves growth and development but inhibitory effects on photoassimilatory pigments. Spruce bark extract reduced the germination capacity of soybean seeds, but accelerated the germination process of sunflower seeds and present stimulatory effects on plantlets biomass accumulation. The combination of DDW with Picea abies polyphenolic extract promoted soybean plantlet elongation, especially the rootlets ones and stimulated green biomass accumulation for both soybean and sunflower plantlets. Analyzing the photoassimilatory pigments concentration for sunflower, it can be observed an increasing trend (almost 100% comparing with control when introduce into the growth medium DDW and P. abies polyphenolic extract. DDW and P. abies bark extract have shown an important role in plant growth and development, improving photoassimiliation process.

  1. Targeted silencing of DNA-specific B cells combined with partial plasma cell depletion displays additive effects on delaying disease onset in lupus-prone mice.

    Science.gov (United States)

    Nikolova-Ganeva, K A; Gesheva, V V; Todorov, T A; Voll, R E; Vassilev, T L

    2013-11-01

    Targeting autoreactive B lymphocytes at any stage of their differentiation could yield viable therapeutic strategies for treating autoimmunity. All currently used drugs, including the most recently introduced biological agents, lack target specificity. Selective silencing of double-stranded DNA-specific B cells in animals with spontaneous lupus has been achieved previously by the administration of a chimeric antibody molecule that cross-links their DNA-reactive B cell immunoglobulin receptors with inhibitory FcγIIb (CD32) receptors. However, long-lived plasmacytes are resistant to this chimeric antibody as well as to all conventional treatments. Bortezomib (a proteasome inhibitor) depletes most plasma cells and has been shown recently to suppress disease activity in lupus mice. We hypothesized that the co-administration of non-toxic doses of bortezomib, that partially purge long-lived plasma cells, together with an agent that selectively silences DNA-specific B cells, should have additive effects in an autoantibody-mediated disease. Indeed, our data show that the simultaneous treatment of lupus-prone MRL/lpr mice with suboptimal doses of bortezomib plus the chimeric antibody resulted in the prevention or the delayed appearance of the disease manifestations as well as in a prolonged survival. The effect of the combination therapy was significantly stronger than that of the respective monotherapies and was comparable to that observed after cyclophosphamide administration.

  2. Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice.

    Science.gov (United States)

    Sakaguchi, Satoshi; Goto, Hisatsugu; Hanibuchi, Masaki; Otsuka, Shinsaku; Ogino, Hirokazu; Kakiuchi, Soji; Uehara, Hisanori; Yano, Seiji; Nishioka, Yasuhiko; Sone, Saburo

    2010-05-01

    Lung cancer frequently develops multiple organ metastases, which thus makes this disease a leading cause of malignancy-related death worldwide. A gender difference is reported to affect the incidence and mortality of lung cancer; however, whether and how the gender difference is involved in lung cancer metastasis is unclear. This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid hormone-related protein (PTHrP) associated with gender or androgen suppression. An in vitro study also indicated that sex steroid treatment had no effect on the proliferation or PTHrP production in SBC-5 cells. These results indicate that the balance of sex steroids therefore plays an important role in the formation of bone metastasis in small cell lung cancer, and suggests diverse mechanisms of interaction between cancer cells and host cells in the bone microenvironment.

  3. Local and Global Impacts of Carbon Capture and Storage Combined with Enhanced Oil Recovery in Four Depleted Oil Fields, Kern County, California

    Science.gov (United States)

    Gillespie, J.; Jordan, P. D.; Goodell, J. A.; Harrington, K.; Jameson, S.

    2015-12-01

    Depleted oil reservoirs are attractive targets for geologic carbon storage (GCS) because they possess proven trapping mechanisms and large amounts of data pertaining to production and reservoir geometry. In addition, CO2 enhanced oil recovery (EOR) can improve recovery of the remaining oil at recovery factors of 6 to 20% of original oil in place in appropriate reservoirs. CO2 EOR increases the attractiveness of depleted oil and gas reservoirs as a starting point for CCS because the CO2 becomes a commodity that can be purchased by field operators for EOR purposes thereby offsetting the costs of CO2 capture at the power plant. In California, Kern County contains the largest oil reservoirs and produces 76% of California's oil. Most of the production at depths suitable for CCS combined with CO2 EOR comes from three reservoirs: the Vedder and Temblor formations and the Stevens Sandstone of the Monterey Formation. These formations were evaluated for GCS and CO2 EOR potential at the North and South Coles Levee (Stevens Sandstone), Greeley (Vedder) and McKittrick (Temblor) fields. CO2 EOR could be expected to produce an additional 150 million bbls of oil. The total storage space created by pre- and post-EOR fluid production for all three reservoirs is approximately 104 million metric tons (MMT). Large fixed sources in California produce 156 MMT/yr of CO2, and sources in Kern County produce 26 MMT/yr (WESTCARB, 2012). Therefore, the fields could store about four years of local large fixed source emissions and about two thirds of statewide emissions. However, from a global perspective, burning the additional oil produced by CO2 EOR would generate an additional 65 MMT of CO2 if not captured. This would result in a net reduction of greenhouse gas of only 39 MMT rather than the full 104 MMT. If the water produced along with the oil recovered during CO2 EOR operations is not reinjected into the reservoir, the storage space could be much higher.

  4. Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor

    Science.gov (United States)

    Huang, Yunfei; Higginson, Daniel S.; Hester, Lynda; Park, Myung Hee; Snyder, Solomon H.

    2007-01-01

    Eukaryotic translation initiation factor 5A (eIF5A), the only known protein containing the polyamine-derived amino acid hypusine, modulates protein synthesis. We show that neurotrophic and neuroprotective actions of nerve growth factor (NGF) are mediated by hypusinated eIF5A, which can account for the known roles of polyamines in cell growth and survival. NGF treatment of PC12 cells stimulates eIF5A formation. Moreover, prevention of hypusine formation by a selective inhibitor of deoxyhypusine synthase and by its depletion with RNA interference blocks the NGF-elicited augmentation of neurite outgrowth and cell survival of PC12 cells. In brain cultures, inhibition of hypusine formation also inhibits neuronal process extension. PMID:17360499

  5. Polyamine Metabolism in Fungi with Emphasis on Phytopathogenic Species

    Directory of Open Access Journals (Sweden)

    Laura Valdés-Santiago

    2012-01-01

    Full Text Available Polyamines are essential metabolites present in all living organisms, and this subject has attracted the attention of researchers worldwide interested in defining their mode of action in the variable cell functions in which they are involved, from growth to development and differentiation. Although the mechanism of polyamine synthesis is almost universal, different biological groups show interesting differences in this aspect that require to be further analyzed. For these studies, fungi represent interesting models because of their characteristics and facility of analysis. During the last decades fungi have contributed to the understanding of polyamine metabolism. The use of specific inhibitors and the isolation of mutants have allowed the manipulation of the pathway providing information on its regulation. During host-fungus interaction polyamine metabolism suffers striking changes in response to infection, which requires examination. Additionally the role of polyamine transporter is getting importance because of its role in polyamine regulation. In this paper we analyze the metabolism of polyamines in fungi, and the difference of this process with other biological groups. Of particular importance is the difference of polyamine biosynthesis between fungi and plants, which makes this process an attractive target for the control of phytopathogenic fungi.

  6. Polyamines as redox homeostasis regulators during salt stress in plants

    Directory of Open Access Journals (Sweden)

    Jayita eSaha

    2015-04-01

    Full Text Available The balance between accumulation of stress-induced polyamines and reactive oxygen species (ROS is arguably a critical factor in plant tolerance to salt stress. Polyamines are compounds, which accumulate in plants under salt stress and help maintain cellular ROS homeostasis. In this review we first outline the role of polyamines in mediating salt stress responses through their modulation of redox homeostasis. The two proposed roles of polyamines in regulating ROS – as antioxidative molecules and source of ROS synthesis – are discussed and exemplified with recent studies. Second, the proposed function of polyamines as modulators of ion transport is discussed in the context of plant salt stress. Finally, we highlight the apparent connection between polyamine accumulation and programmed cell death induction during stress. Thus polyamines have a complex functional role in regulating cellular signaling and metabolism during stress. By focusing future efforts on how polyamine accumulation and turnover is regulated, research in this area may provide novel targets for developing stress tolerance.

  7. Transgenic manipulation of the metabolism of polyamines in poplar cells

    Science.gov (United States)

    Pratiksha Bhatnagar; Bernadette M. Glasheen; Suneet K. Bains; Stephanie L. Long; Rakesh Minocha; Christian Walter; Subhash C. Minocha

    2001-01-01

    The metabolism of polyamines (putrescine, spermidine, and spermine) has become the target of genetic manipulation because of their significance in plant development and possibly stress tolerance. We studied the polyamine metabolism in non-transgenic (NT) and transgenic cells of poplar (Populus nigra 3 maximowiczii) expressing a...

  8. Ornithine: the overlooked molecule in the regulation of polyamine metabolism

    Science.gov (United States)

    Rajtilak Majumdar; Lin Shao; Rakesh Minocha; Stephanie Long; Subhash C. Minocha

    2013-01-01

    We overexpressed a mouse ornithine decarboxylase gene under the control of a constitutive and an estradiol-inducible promoter in Arabidopsis thaliana to increase our understanding of the regulation of polyamine metabolism. Of particular interest was the role of the substrate ornithine not only in the regulation of polyamine biosynthesis, but also in...

  9. Natural Product Polyamines That Inhibit Human Carbonic Anhydrases

    Directory of Open Access Journals (Sweden)

    Rohan A. Davis

    2014-01-01

    Full Text Available Natural product compound collections have proven an effective way to access chemical diversity and recent findings have identified phenolic, coumarin, and polyamine natural products as atypical chemotypes that inhibit carbonic anhydrases (CAs. CA enzymes are implicated as targets of variable drug therapeutic classes and the discovery of selective, drug-like CA inhibitors is essential. Just two natural product polyamines, spermine and spermidine, have until now been investigated as CA inhibitors. In this study, five more complex natural product polyamines 1–5, derived from either marine sponge or fungi, were considered for inhibition of six different human CA isozymes of interest in therapeutic drug development. All compounds share a simple polyamine core fragment, either spermine or spermidine, yet display substantially different structure activity relationships for CA inhibition. Notably, polyamines 1–5 were submicromolar inhibitors of the cancer drug target CA IX, this is more potent than either spermine or spermidine.

  10. Learning about ozone depletion

    Energy Technology Data Exchange (ETDEWEB)

    Crutzen, J. P. [Department of Atmospheric Chemistry, Max Planck Institute for Chemistry, Mainz, Germany; Oppenheimer M. [Woodrow Wilson School of Public and International Affairs, Department of Geosciences, Princeton University, Princeton, NJ (United States)

    2008-07-15

    Stratospheric ozone depletion has been much studied as a case history in the interaction between environmental science and environmental policy. The positive influence of science on policy is often underscored, but here we review the photochemistry of ozone in order to illustrate how scientific learning has the potential to mislead policy makers. The latter may occur particularly in circumstances where limited observations are combined with simplified models of a complex system, such as may generally occur in the global change arena. Even for the well-studied case of ozone depletion, further research is needed on the dynamics of scientific learning, particularly the scientific assessment process, and how assessments influence the development of public policy.

  11. Mechanism of polyamine tolerance in yeast: novel regulators and insights.

    Science.gov (United States)

    Porat, Z; Wender, N; Erez, O; Kahana, C

    2005-12-01

    Polyamines are small charged molecules essential for various cellular functions, but at high levels they are cytotoxic. Two yeast kinases, SKY1 and PTK2, have been demonstrated to regulate polyamine tolerance. Here we report the identification and characterization of additional genes involved in regulating polyamine tolerance: YGL007W, FES1 and AGP2. Deletion of YGL007W, an open reading frame located within the promoter of the membrane proton pump PMA1, decreased Pma1p expression. Deletion of FES1 or AGP2 resulted in reduced polyamine uptake. While high-affinity spermine uptake was practically absent in agp2Delta cells, fes1Delta cells displayed only reduced affinity towards spermine. Despite the reduced uptake, the resistant strains accumulated significant levels of polyamines and displayed increased ornithine decarboxylase activity, suggesting reduced polyamine sensing. Interestingly, fes1Delta cells were highly sensitive to salt ions, suggesting different underlying mechanisms. These results indicate that mechanisms leading to polyamine tolerance are complex, and involve components other than uptake.

  12. Characteristics of cellular polyamine transport in prokaryotes and eukaryotes.

    Science.gov (United States)

    Igarashi, Kazuei; Kashiwagi, Keiko

    2010-07-01

    Polyamine content in cells is regulated by biosynthesis, degradation and transport. In Escherichia coli, there are two polyamine uptake systems, namely spermidine-preferential (PotABCD) and putrescine-specific (PotFGHI), which belong to the family of ATP binding cassette transporters. Putrescine-ornithine and cadaverine-lysine antiporters, PotE and CadB, each consisting of 12 transmembrane segments, are important for cell growth at acidic pH. Spermidine excretion protein (MdtJI) was also recently identified. When putrescine was used as energy source, PuuP functioned as a putrescine transporter. In Saccharomyces cerevisiae, there are four kinds of polyamine uptake proteins (DUR3, SAM3, GAP1 and AGP2), consisting of either 12 or 16 transmembrane segments. Among them, DUR3 and SAM3 mostly contribute to polyamine uptake. There are also five kinds of polyamine excretion proteins (TPO1-5), consisting of 12 transmembrane segments. Among them, TPO1 and TPO5 are the most active proteins. Since a polyamine metabolizing enzyme, spermidine/spermine N(1)-acetyltransferase, is not present in yeast, five kinds of excretion proteins may exist. The current status of polyamine transport in mammalian and plant cells are reviewed.

  13. General synthesis of β-alanine-containing spider polyamine toxins and discovery of nephila polyamine toxins 1 and 8 as highly potent inhibitors of ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Lucas, Simon; Poulsen, Mette H; Nørager, Niels G

    2012-01-01

    Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotrop...

  14. Polyamine Metabolism and Osmotic Stress 1

    Science.gov (United States)

    Tiburcio, Antonio Fernández; Kaur-Sawhney, Ravindar; Galston, Arthur W.

    1986-01-01

    We have attempted to improve the viability of cereal mesophyll protoplasts by pretreatment of leaves with dl-α-difluoromethylarginine (DFMA), a specific `suicide' inhibitor of the enzyme (arginine decarboxylase) responsible for their osmotically induced putrescine accumulation. Leaf pretreatment with DFMA before a 6 hour osmotic shock caused a 45% decrease of putrescine and a 2-fold increase of spermine titer. After 136 hours of osmotic stress, putrescine titer in DFMA-pretreated leaves increased by only 50%, but spermidine and spermine titers increased dramatically by 3.2- and 6-fold, respectively. These increases in higher polyamines could account for the reduced chlorophyll loss and enhanced ability of pretreated leaves to incorporate tritiated thymidine, uridine, and leucine into macromolecules. Pretreatment with DFMA significantly improved the overall viability of the protoplasts isolated from these leaves. The results support the view that the osmotically induced rise in putrescine and blockage of its conversion to higher polyamines may contribute to the lack of sustained cell division in cereal mesophyll protoplasts, although other undefined factors must also play a major role. PMID:11539087

  15. Effects of polyamines on K+,Na+ and Cl- content and distribution in different organs of cucumber (Cucumis sativus L.) seedlings under NaCl stress

    Institute of Scientific and Technical Information of China (English)

    WANG Suping; JIA Yongxia; GUO Shirong; ZHOU Guoxian

    2007-01-01

    Seedlings from the salt-sensitive cucumber cultivar Jinchun No.2 and the salt-tolerant cucumber cultivar Changchun Mici were exposed for 8 days to 50 mmol/L NaCl in the absence or in the presence of exogenous foliar spraying PAs [putrescine (Put),spermidine (Spd),and spermine (Spin)1 mmol/L] to compare the effects of different kinds of polyamines (PAs) on plant tolerance to salinity.This paper studied the effects of exogenous PAs on K+,Na+ and Cl- in different organs of cucumber seedlings.The results showed that K+ content as well as the ratios of K/Na and Cl/Na decreased,while Na+ and Cl- concentrations increased in salt-treated cucumber seedlings.The differences in K+,Na+ and Cl- content and the K/Na and Cl/Na ratios were greater for the salt sensitive cultivar Jinchun No.2 than for the salt-tolerant cultivar Changchun Mici.Cucumber seedlings treated with exogenous polyamines and combined with salinity exhibited a higher level of K+ accumulation and lower levels of Na+ and Cl- accumulation compared with the seedlings treated only with salt stress.Among the three kinds of polyamines,Spd and Spm were more effective in inhibiting the accumulation of Na+ and reduction of K+.However,Put was more effective in reducing Cl- accumulation.Furthermore,all of the three kinds of exogenous polyamines could increase the ratio of K/Na,improving the absorption and transport selectivities of K+ and Na+ from stems to leaves for both cultivars.In conclusion,exogenous polyamines could alleviate salt damage to some extent and enhance the accumulation of biomass.Among the three kinds of polyamines,spermidine was most effective.Exogenous polyamines could improve tolerance of cucumber seedlings under salt stress by regulating the absorption and distribution of ions in different organs.

  16. Properties of purified recombinant human polyamine oxidase, PAOh1/SMO.

    Science.gov (United States)

    Wang, Yanlin; Murray-Stewart, Tracy; Devereux, Wendy; Hacker, Amy; Frydman, Benjamin; Woster, Patrick M; Casero, Robert A

    2003-05-16

    The discovery of an inducible oxidase whose apparent substrate preference is spermine indicates that polyamine catabolism is more complex than that originally proposed. To facilitate the study of this enzyme, the purification and characterization of the recombinant human PAOh1/SMO polyamine oxidase are reported. Purified PAOh1/SMO oxidizes both spermine (K(m)=1.6 microM) and N(1)-acetylspermine (K(m)=51 microM), but does not oxidize spermidine. The purified human enzyme also does not oxidize eight representative antitumor polyamine analogues; however, specific oligamine analogues were found to be potent inhibitors of the oxidation of spermine by PAOh1/SMO. The results of these studies are consistent with the hypothesis that PAOh1/SMO represents a new addition to the polyamine metabolic pathway that may represent a new target for antineoplastic drug development.

  17. Targeting polyamine metabolism for cancer therapy and prevention.

    Science.gov (United States)

    Murray-Stewart, Tracy R; Woster, Patrick M; Casero, Robert A

    2016-10-01

    The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention.

  18. Polyamines Are Required for Virulence in Salmonella enterica Serovar Typhimurium

    DEFF Research Database (Denmark)

    Jelsbak, Lotte; Thomsen, Line Elnif; Wallrodt, Inke

    2012-01-01

    Sensing and responding to environmental cues is a fundamental characteristic of bacterial physiology and virulence. Here we identify polyamines as novel environmental signals essential for virulence of Salmonella enterica serovar Typhimurium, a major intracellular pathogen and a model organism fo...

  19. Polyamine interactions with plant hormones: crosstalk at several levels

    Science.gov (United States)

    Polyamines play important roles in diverse plant growth and development processes including seed germination, tissue lignification, organogenesis, flowering, pollination, embryogenesis, fruit development, ripening, abscission, senescence and stress responses. In all these processes, synergistic and ...

  20. Cellular content and biosynthesis of polyamines during rooster spermatogenesis.

    Science.gov (United States)

    Oliva, R; Vidal, S; Mezquita, C

    1982-11-15

    The natural polyamines spermine and spermidine, and the diamine putrescine, were extracted from rooster testis cells separated by sedimentation at unit gravity, and from vas-deferens spermatozoa. The ratios spermine/DNA and spermidine/DNA were kept relatively constant throughout spermatogenesis, whereas the ratio putrescine/DNA rose in elongated spermatids. The cellular content of spermine, spermidine and putrescine decreased markedly in mature spermatozoa. Two rate-limiting enzymes in the biosynthetic pathway of polyamines, ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, showed their highest activities at the end of spermiogenesis and were not detectable in vas-deferens spermatozoa. A marked reduction in cell volume during spermiogenesis without a parallel decrease in the cellular content of polyamines suggests the possibility that the marked changes in chromatin composition and structure occurring in rooster late spermatids could take place in an ambience of high polyamine concentration.

  1. Polyamines Are Required for Virulence in Salmonella enterica Serovar Typhimurium

    DEFF Research Database (Denmark)

    Jelsbak, Lotte; Thomsen, Line Elnif; Wallrodt, Inke;

    2012-01-01

    Sensing and responding to environmental cues is a fundamental characteristic of bacterial physiology and virulence. Here we identify polyamines as novel environmental signals essential for virulence of Salmonella enterica serovar Typhimurium, a major intracellular pathogen and a model organism......, we show that an S. Typhimurium polyamine mutant is defective for invasion, intracellular survival, killing of the nematode Caenorhabditis elegans and systemic infection of the mouse model of typhoid fever. Virulence of the mutant could be restored by genetic complementation, and invasion...

  2. Polyamine synthesis and interconversion by the Microsporidian Encephalitozoon cuniculi.

    Science.gov (United States)

    Bacchi, C J; Lane, S; Weiss, L M; Yarlett, N; Takvorian, P; Cali, A; Wittner, M

    2001-01-01

    Polyamines are small cationic molecules necessary for growth and differentiation in all cells. Although mammalian cells have been studied extensively, particularly as targets of polyamine antagonists, i.e. antitumor agents, polyamine metabolism has also been studied as a potential drug target in microorganisms. Since little is known concerning polyamine metabolism in the microsporidia, we investigated it in Encephalitozoon cuniculi, a microspordian associated with disseminated infections in humans. Organisms were grown in RK-13 cells and harvested using Percoll gradients. Electron microscopy indicated that the fractions banding at 1.051-1.059/g/ml in a microgradient procedure, and 1.102-1.119/g/ml in a scaled-up procedure were nearly homogenous, consisting of pre-emergent (immature) spores which showed large arrays of ribosomes near polar filament coils. Intact purified pre-emergent spores incubated with [1H] ornithine and methionine synthesized putrescine, spermidine, and spermine, while [14C]spermine was converted to spermidine and putrescine. Polyamine production from ornithine was inhibitable by DL-alpha-difluoromethylornithine (DFMO) but not by DL-alpha-difluoromethylarginine (DFMA). Cell-free extracts from mature spores released into the growth media had ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetdc), and spermidine/spermine N1-acetyltransferase (SSAT) activities. ODC activity was inhibited by DFMO, but not by DFMA. AdoMetdc was putrescine-stimulated and inhibited by methylglyoxal-bis(guanylhydrazone); arginine decarboxylase activity could not be detected. It is apparent from these studies that Encephalitozoon cuniculi pre-emergent spores have a eukaryotic-type polyamine biosynthetic pathway and can interconvert exogenous polyamines. Pre-emergent spores were metabolically active with respect to polyamine synthesis and interconversion, while intact mature spores harvested from culture supernatants had little metabolic activity.

  3. Polyamine-independent Expression of Caenorhabditis elegans Antizyme.

    Science.gov (United States)

    Stegehake, Dirk; Kurosinski, Marc-André; Schürmann, Sabine; Daniel, Jens; Lüersen, Kai; Liebau, Eva

    2015-07-17

    Degradation of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis, is promoted by the protein antizyme. Expression of antizyme is positively regulated by rising polyamine concentrations that induce a +1 translational frameshift required for production of the full-length protein. Antizyme itself is negatively regulated by the antizyme inhibitor. In our study, the regulation of Caenorhabditis elegans antizyme was investigated, and the antizyme inhibitor was identified. By applying a novel GFP-based method to monitor antizyme frameshifting in vivo, we show that the induction of translational frameshifting also occurs under stressful conditions. Interestingly, during starvation, the initiation of frameshifting was independent of polyamine concentrations. Because frameshifting was also prevalent in a polyamine auxotroph double mutant, a polyamine-independent regulation of antizyme frameshifting is suggested. Polyamine-independent induction of antizyme expression was found to be negatively regulated by the peptide transporter PEPT-1, as well as the target of rapamycin, but not by the daf-2 insulin signaling pathway. Stress-dependent expression of C. elegans antizyme occurred morely slowly than expression in response to increased polyamine levels, pointing to a more general reaction to unfavorable conditions and a diversion away from proliferation and reproduction toward conservation of energy. Interestingly, antizyme expression was found to drastically increase in aging individuals in a postreproductive manner. Although knockdown of antizyme did not affect the lifespan of C. elegans, knockdown of the antizyme inhibitor led to a significant reduction in lifespan. This is most likely caused by an increase in antizyme-mediated degradation of ornithine decarboxylase-1 and a resulting reduction in cellular polyamine levels.

  4. Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi, Maria Lauda [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); Ryoo, Minjung; Skay, Anna [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); Tomasi, Ivan; Giordano, Pasquale [Department of Colorectal Surgery, Whipps Cross University Hospital, London E11 1NR (United Kingdom); Mato, José M. [CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia (Spain); Lu, Shelly C., E-mail: shellylu@usc.edu [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States)

    2013-07-15

    Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70–75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100 pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell. -- Highlights: • MAT2A knockdown depletes putrescine and leads to apoptosis. • Putrescine attenuates MAT2A knockdown-induced apoptosis and growth

  5. Polyamine-Induced Rapid Root Abscission in Azolla pinnata

    Directory of Open Access Journals (Sweden)

    Sushma Gurung

    2012-01-01

    Full Text Available Floating ferns of the genus Azolla detach their roots under stress conditions, a unique adaptive response termed rapid root abscission. We found that Azolla pinnata plants exhibited dose-dependent rapid root abscission in response to the polyamines spermidine and spermine after a substantial time lag (>20 min. The duration of the time lag decreased in response to high pH and high temperature whereas high light intensity increased the time lag and markedly lowered the rate of abscission. The oxidation products of polyamines, 1,3-diaminopropane, β-alanine and hydrogen peroxide all failed to initiate root abscission, and hydroxyethyl hydrazine, an inhibitor of polyamine oxidase, did not inhibit spermine-induced root abscission. Exposure of A. pinnata to the polyamines did not result in detectable release of NO and did not affect nitrite-dependent NO production. The finding of polyamine-induced rapid root abscission provides a facile assay for further study of the mode of action of polyamines in plant stress responses.

  6. Polyamine-Induced Rapid Root Abscission in Azolla pinnata.

    Science.gov (United States)

    Gurung, Sushma; Cohen, Michael F; Fukuto, Jon; Yamasaki, Hideo

    2012-01-01

    Floating ferns of the genus Azolla detach their roots under stress conditions, a unique adaptive response termed rapid root abscission. We found that Azolla pinnata plants exhibited dose-dependent rapid root abscission in response to the polyamines spermidine and spermine after a substantial time lag (>20 min). The duration of the time lag decreased in response to high pH and high temperature whereas high light intensity increased the time lag and markedly lowered the rate of abscission. The oxidation products of polyamines, 1,3-diaminopropane, β-alanine and hydrogen peroxide all failed to initiate root abscission, and hydroxyethyl hydrazine, an inhibitor of polyamine oxidase, did not inhibit spermine-induced root abscission. Exposure of A. pinnata to the polyamines did not result in detectable release of NO and did not affect nitrite-dependent NO production. The finding of polyamine-induced rapid root abscission provides a facile assay for further study of the mode of action of polyamines in plant stress responses.

  7. Polyamine uptake by DUR3 and SAM3 in Saccharomyces cerevisiae.

    Science.gov (United States)

    Uemura, Takeshi; Kashiwagi, Keiko; Igarashi, Kazuei

    2007-03-09

    It has been reported that GAP1 and AGP2 catalyze the uptake of polyamines together with amino acids in Saccharomyces cerevisiae. We have looked for polyamine-preferential uptake proteins in S. cerevisiae. DUR3 catalyzed the uptake of polyamines together with urea, and SAM3 was found to catalyze the uptake of polyamines together with S-adenosylmethionine, glutamic acid, and lysine. Polyamine uptake was greatly decreased in both DUR3- and SAM3-deficient cells. The K(m) values for putrescine and spermidine of DUR3 were 479 and 21.2 mum, respectively, and those of SAM3 were 433 and 20.7 mum, respectively. Polyamine stimulation of cell growth of a polyamine requiring mutant, which is deficient in ornithine decarboxylase, was not influenced by the disruption of GAP1 and AGP2, but it was diminished by the disruption of DUR3 and SAM3. Furthermore, the polyamine stimulation of cell growth of a polyamine-requiring mutant was completely inhibited by the disruption of both DUR3 and SAM3. The results indicate that DUR3 and SAM3 are major polyamine uptake proteins in yeast. We previously reported that polyamine transport protein kinase 2 regulates polyamine transport. It was found that DUR3 (but not SAM3) was activated by phosphorylation of Thr(250), Ser(251), and Thr(684) by polyamine transport protein kinase 2.

  8. Modulation of Higher Order Chromatin Conformation in Mammalian Cell Nuclei Can Be Mediated by Polyamines and Divalent Cations.

    Directory of Open Access Journals (Sweden)

    Ashwat Visvanathan

    Full Text Available The organisation of the large volume of mammalian genomic DNA within cell nuclei requires mechanisms to regulate chromatin compaction involving the reversible formation of higher order structures. The compaction state of chromatin varies between interphase and mitosis and is also subject to rapid and reversible change upon ATP depletion/repletion. In this study we have investigated mechanisms that may be involved in promoting the hyper-condensation of chromatin when ATP levels are depleted by treating cells with sodium azide and 2-deoxyglucose. Chromatin conformation was analysed in both live and permeabilised HeLa cells using FLIM-FRET, high resolution fluorescence microscopy and by electron spectroscopic imaging microscopy. We show that chromatin compaction following ATP depletion is not caused by loss of transcription activity and that it can occur at a similar level in both interphase and mitotic cells. Analysis of both live and permeabilised HeLa cells shows that chromatin conformation within nuclei is strongly influenced by the levels of divalent cations, including calcium and magnesium. While ATP depletion results in an increase in the level of unbound calcium, chromatin condensation still occurs even in the presence of a calcium chelator. Chromatin compaction is shown to be strongly affected by small changes in the levels of polyamines, including spermine and spermidine. The data are consistent with a model in which the increased intracellular pool of polyamines and divalent cations, resulting from depletion of ATP, bind to DNA and contribute to the large scale hyper-compaction of chromatin by a charge neutralisation mechanism.

  9. Naturally occurring branched-chain polyamines induce a crosslinked meshwork structure in a giant DNA

    Science.gov (United States)

    Muramatsu, Akira; Shimizu, Yuta; Yoshikawa, Yuko; Fukuda, Wakao; Umezawa, Naoki; Horai, Yuhei; Higuchi, Tsunehiko; Fujiwara, Shinsuke; Imanaka, Tadayuki; Yoshikawa, Kenichi

    2016-12-01

    We studied the effect of branched-chain polyamines on the folding transition of genome-sized DNA molecules in aqueous solution by the use of single-molecule observation with fluorescence microcopy. Detailed morphological features of polyamine/DNA complexes were characterized by atomic force microscopy (AFM). The AFM observations indicated that branched-chain polyamines tend to induce a characteristic change in the higher-order structure of DNA by forming bridges or crosslinks between the segments of a DNA molecule. In contrast, natural linear-chain polyamines cause a parallel alignment between DNA segments. Circular dichroism measurements revealed that branched-chain polyamines induce the A-form in the secondary structure of DNA, while linear-chain polyamines have only a minimum effect. This large difference in the effects of branched- and linear-chain polyamines is discussed in relation to the difference in the manner of binding of these polyamines to negatively charged double-stranded DNA.

  10. Thermodynamic analysis of biogenic and synthetic polyamines conjugation with PAMAM-G4 nanoparticles.

    Science.gov (United States)

    Chanphai, P; Tajmir-Riahi, H A

    2016-02-01

    We report the thermodynamic analysis of the bindings of poly(amidoamine) (PAMAM-G4) nanoparticles with biogenic polyamines spermine (spm), spermidine (spmd) and synthetic polyamines 3,7,11,15-tetrazaheptadecane·4HCl (BE-333) in aqueous solution at physiological conditions. Multiple spectroscopic methods, thermodynamic parameters and molecular modelling were used to analyse polyamine bindings to PAMAM dendrimers. Thermodynamic parameters ΔS, ΔH and ΔG parameters showed that polyamines bind polymer through H-bonding and van der Waals contacts with biogenic polyamines form more stable conjugates than synthetic polyamines. Modelling showed that polyamines are located at the surface of PAMAM with the free binding energy of -3.56 (spermine), -3.88 (spermidine) and -3.13 kcal/mol (BE-333), indicating spontaneous polyamine-polymer interaction at room temperature.

  11. Polyamines and abiotic stress in plants: A complex relationship

    Directory of Open Access Journals (Sweden)

    Rakesh eMinocha

    2014-05-01

    Full Text Available The physiological relationship between abiotic stress in plants and polyamines was reported more than 40 years ago. Ever since there has been a debate as to whether increased polyamines protect plants against abiotic stress (e.g. due to their ability to deal with oxidative radicals or cause damage to them (perhaps due to hydrogen peroxide produced by their catabolism. The observation that cellular polyamines are typically elevated in plants under both short-term as well as long-term abiotic stress conditions is consistent with the possibility of their dual effects, i.e. being a protector as well as a perpetrator of stress damage to the cells. The observed increase in tolerance of plants to abiotic stress when their cellular contents are elevated by either exogenous treatment with polyamines or through genetic engineering with genes encoding polyamine biosynthetic enzymes is indicative of a protective role for them. However, through their catabolic production of hydrogen peroxide and acrolein, both strong oxidizers, they can potentially be the cause of cellular harm during stress. In fact, somewhat enigmatic but strong positive relationship between abiotic stress and foliar polyamines has been proposed as a potential biochemical marker of persistent environmental stress in forest trees in which phenotypic symptoms of stress are not yet visible. Such markers may help forewarn forest managers to undertake amelioration strategies before the appearance of visual symptoms of stress and damage at which stage it is often too late for implementing strategies for stress remediation and reversal of damage. This review provides a comprehensive and critical evaluation of the published literature on interactions between abiotic stress and polyamines in plants, and examines the experimental strategies used to understand the functional significance of this relationship with the aim of improving plant productivity, especially under conditions of abiotic stress.

  12. Effect of polyamines and synthetic polyamine-analogues on the expression of antizyme (AtoC and its regulatory genes

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    Garnelis Thomas

    2007-01-01

    Full Text Available Abstract Background In bacteria, the biosynthesis of polyamines is modulated at the level of transcription as well as post-translationally. Antizyme (Az has long been identified as a non-competitive protein inhibitor of polyamine biosynthesis in E. coli. Az was also revealed to be the product of the atoC gene. AtoC is the response regulator of the AtoS-AtoC two-component system and it functions as the positive transcriptional regulator of the atoDAEB operon genes, encoding enzymes involved in short chain fatty acid metabolism. The antizyme is referred to as AtoC/Az, to indicate its dual function as both a transcriptional and post-translational regulator. Results The roles of polyamines on the transcription of atoS and atoC genes as well as that of atoDAEB(ato operon were studied. Polyamine-mediated induction was tested both in atoSC positive and negative E. coli backgrounds by using β-galactosidase reporter constructs carrying the appropriate promoters patoDAEB, patoS, patoC. In addition, a selection of synthetic polyamine analogues have been synthesized and tested for their effectiveness in inducing the expression of atoC/Az, the product of which plays a pivotal role in the feedback inhibition of putrescine biosynthesis and the transcriptional regulation of the ato operon. The effects of these compounds were also determined on the ato operon expression. The polyamine analogues were also tested for their effect on the activity of ornithine decarboxylase (ODC, the key enzyme of polyamine biosynthesis and on the growth of polyamine-deficient E. coli. Conclusion Polyamines, which have been reported to induce the protein levels of AtoC/Az in E. coli, act at the transcriptional level, since they cause activation of the atoC transcription. In addition, a series of polyamine analogues were studied on the transcription of atoC gene and ODC activity.

  13. Effects of dicyclohexylamine on polyamine biosynthesis and incorporation into turnip yellow mosaic virus in Chinese cabbage protoplasts infected in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Balint, R.; Cohen, S.S.

    1985-07-15

    The authors have reported that protoplasts from plants infected with turnip yellow mosaic virus (TYMV) continue to produce virus in culture and that newly formed virus particles contained predominantly newly synthesized spermidine and spermine. They now report similar results with healthy protoplasts infected in vitro, in which essentially all of the virus is newly formed. Again, newly synthesized spermidine and spermine were preferentially incorporated into virus. DCHA inhibited spermidine synthesis by 85%, leading in 20 hr to a 60% depletion of the cellular spermidine and a 30% reduction in the amount of spermidine per virion. Spermine synthesis increased, however, producing a 40% increase in cellular spermine and 50-100% increase in the amount of spermine per virion. Thus, in spite of spermidine depletion, the total positive charge contributed by polyamines to the virus was essentially conserved.

  14. Probing tRNA interaction with biogenic polyamines.

    Science.gov (United States)

    Ouameur, Amin Ahmed; Bourassa, Philippe; Tajmir-Riahi, Heidar-Ali

    2010-10-01

    Biogenic polyamines are found to modulate protein synthesis at different levels. This effect may be explained by the ability of polyamines to bind and influence the secondary structure of tRNA, mRNA, and rRNA. We report the interaction between tRNA and the three biogenic polyamines putrescine, spermidine, spermine, and cobalt(III)hexamine at physiological conditions, using FTIR spectroscopy, capillary electrophoresis, and molecular modeling. The results indicated that tRNA was stabilized at low biogenic polyamine concentration, as a consequence of polyamine interaction with the backbone phosphate group. The main tRNA reactive sites for biogenic polyamine at low concentration were guanine-N7/O6, uracil-O2/O4, adenine-N3, and 2'OH of the ribose. At high polyamine concentration, the interaction involves guanine-N7/O6, adenine-N7, uracil-O2 reactive sites, and the backbone phosphate group. The participation of the polycation primary amino group, in the interaction and the presence of the hydrophobic contact, are also shown. The binding affinity of biogenic polyamine to tRNA molecule was in the order of spermine > spermidine > putrescine with K(Spm) = 8.7 × 10(5) M(-1), K(Spd) = 6.1 × 10(5) M(-1), and K(Put) = 1.0 × 10(5) M(-1), which correlates with their positively charged amino group content. Hill analysis showed positive cooperativity for the biogenic polyamines and negative cooperativity for cobalt-hexamine. Cobalt(III)hexamine contains high- and low-affinity sites in tRNA with K(1) = 3.2 × 10(5) M(-1) and K(2) = 1.7 × 10(5) M(-1), that have been attributed to the interactions with guanine-N7 sites and the backbone PO(2) group, respectively. This mechanism of tRNA binding could explain the condensation phenomenon observed at high Co(III) content, as previously shown in the Co(III)-DNA complexes.

  15. INWARD RECTIFIERS AND THEIR REGULATION BY ENDOGENOUS POLYAMINES

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    Victoria A Baronas

    2014-08-01

    Full Text Available Inwardly-rectifying potassium (Kir channels contribute to maintenance of the resting membrane potential and regulation of electrical excitation in many cell types. Strongly rectifying Kir channels exhibit a very steep voltage dependence resulting in silencing of their activity at depolarized membrane voltages. The mechanism underlying this steep voltage dependence is blockade by endogenous polyamines. These small multifunctional, polyvalent metabolites enter the long Kir channel pore from the intracellular side, displacing multiple occupant ions as they migrate to a stable binding site in the transmembrane region of the channel. Numerous structure-function studies have revealed structural elements of Kir channels that determine their susceptibility to polyamine block, and enable the steep voltage dependence of this process. In addition, various channelopathies have been described that result from alteration of the polyamine sensitivity or activity of strongly rectifying channels. The primary focus of this article is to summarize current knowledge of the molecular mechanisms of polyamine block, and provide some perspective on lingering uncertainties related to this physiologically important mechanism of ion channel blockade. We also briefly review some of the important and well understood physiological roles of polyamine sensitive, strongly rectifying Kir channels, primarily of the Kir2 family.

  16. Polyamines in Pollen: From Microsporogenesis to Fertilization

    Science.gov (United States)

    Aloisi, Iris; Cai, Giampiero; Serafini-Fracassini, Donatella; Del Duca, Stefano

    2016-01-01

    The entire pollen life span is driven by polyamine (PA) homeostasis, achieved through fine regulation of their biosynthesis, oxidation, conjugation, compartmentalization, uptake, and release. The critical role of PAs, from microsporogenesis to pollen–pistil interaction during fertilization, is suggested by high and dynamic transcript levels of PA biosynthetic genes, as well as by the activities of the corresponding enzymes. Moreover, exogenous supply of PAs strongly affects pollen maturation and pollen tube elongation. A reduction of endogenous free PAs impacts pollen viability both in the early stages of pollen development and during fertilization. A number of studies have demonstrated that PAs largely function by modulating transcription, by structuring pollen cell wall, by modulating protein (mainly cytoskeletal) assembly as well as by modulating the level of reactive oxygen species. Both free low-molecular weight aliphatic PAs, and PAs conjugated to proteins and hydroxyl-cinnamic acids take part in these complex processes. Here, we review both historical and recent evidence regarding molecular events underlying the role of PAs during pollen development. In the concluding remarks, the outstanding issues and directions for future research that will further clarify our understanding of PA involvement during pollen life are outlined. PMID:26925074

  17. DNA Interaction Studies of Selected Polyamine Conjugates

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    Marta Szumilak

    2016-09-01

    Full Text Available The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr displacement and DNA unwinding/topoisomerase I/II (Topo I/II activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores.

  18. DNA Interaction Studies of Selected Polyamine Conjugates

    Science.gov (United States)

    Szumilak, Marta; Merecz, Anna; Strek, Malgorzata; Stanczak, Andrzej; Inglot, Tadeusz W.; Karwowski, Boleslaw T.

    2016-01-01

    The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores. PMID:27657041

  19. Polyamines in Pollen: From Microsporogenesis to Fertilization.

    Science.gov (United States)

    Aloisi, Iris; Cai, Giampiero; Serafini-Fracassini, Donatella; Del Duca, Stefano

    2016-01-01

    The entire pollen life span is driven by polyamine (PA) homeostasis, achieved through fine regulation of their biosynthesis, oxidation, conjugation, compartmentalization, uptake, and release. The critical role of PAs, from microsporogenesis to pollen-pistil interaction during fertilization, is suggested by high and dynamic transcript levels of PA biosynthetic genes, as well as by the activities of the corresponding enzymes. Moreover, exogenous supply of PAs strongly affects pollen maturation and pollen tube elongation. A reduction of endogenous free PAs impacts pollen viability both in the early stages of pollen development and during fertilization. A number of studies have demonstrated that PAs largely function by modulating transcription, by structuring pollen cell wall, by modulating protein (mainly cytoskeletal) assembly as well as by modulating the level of reactive oxygen species. Both free low-molecular weight aliphatic PAs, and PAs conjugated to proteins and hydroxyl-cinnamic acids take part in these complex processes. Here, we review both historical and recent evidence regarding molecular events underlying the role of PAs during pollen development. In the concluding remarks, the outstanding issues and directions for future research that will further clarify our understanding of PA involvement during pollen life are outlined.

  20. Polyamine content of long-keeping alcobaca tomato fruit.

    Science.gov (United States)

    Dibble, A R; Davies, P J; Mutschler, M A

    1988-02-01

    Fruit of tomato landrace Alcobaca, containing the recessive allele alc, ripen more slowly, with a reduced level of ethylene production, and have prolonged keeping qualities. The levels of polyamines in pericarp tissues of alc and ;wild type' Alc (cv Rutgers and Alcobaca-red) fruit were measured by HPLC in relation to ripening. Putrescine was the predominant polyamine with a lower content of spermidine, while spermine was just detectable. The level of putrescine was high at the immature green stage and declined in the mature green stage. In Alc fruit the decline persisted but in alc fruit the putrescine level increased during ripening to a level similar to that present at the immature green stage. There was no pronounced change or difference in spermidine levels. The enhanced polyamine level in alc fruit may account for their ripening and storage characteristics.

  1. Polyamines as salinity biochemical marker in callus of eucalyptus urograndis

    Directory of Open Access Journals (Sweden)

    Giuseppina Lima Pace Pereira

    2003-01-01

    Full Text Available Biochemical markers have been used for the analysis of plant cells submitted to several types of stress, among them salinity. This work aimed at analyzing the effect of saline stress in callus of Eucalyptus urograndis on polyamine contents. Explants (hypocotyls obtained from seeds were inoculated in callus inductive medium, submitted to different levels of NaCl and analyzed at 10, 20 and 30 days after the inoculation. The free polyamines were extracted, isolated and quantified using TLC (Thin-Layer Chromatography. Putrescine content was higher and a fall in the spermidine content was observed in callus submitted to salinity condition. The results showed that polyamine accumulation is related to NaCl exposure in callus of Eucalyptus urograndis. The decrease in spermine content could be used as a biochemical marker for Eucalyptus callus subjected to salinity.

  2. Polyamines in conventional and organic vegetables exposed to exogenous ethylene.

    Science.gov (United States)

    Rossetto, Maria Rosecler Miranda; Vianello, Fabio; Saeki, Margarida Juri; Lima, Giuseppina Pace Pereira

    2015-12-01

    Relationships between endogenous levels of polyamines by thin layer chromatography (TLC) and gas chromatography (GC), nitrate and response to the application of ethylene were established between organic and conventional vegetables (broccoli, collard greens, carrots and beets), both raw and cooked. Responses to ethylene showed that organic plants were less responsive to the growth regulator. The levels of free polyamines obtained by TLC were higher in organic vegetables. Organic broccoli showed higher levels of putrescine (Put), and cooking resulted in lowering the overall content of these amines. Conventional collard green showed the highest level of putrescine in the leaves compared with organic. Tubers of carrots and beets contain the highest levels of Put. These plants also contain high levels of spermine. GC analysis showed the highest polyamines contents compared with those obtained by TLC. Cooking process decreased putrescine and cadaverine content, both in conventionally and organically grown vegetables. Organic beets contain lower NO3(-) compared with its conventional counterpart.

  3. BET, thermal degradation, and FTIR spectras of triazine polyamine polymers.

    Science.gov (United States)

    Can, Mustafa

    2017-04-01

    Here we show effect of the polyamine polymer chain length to BET isotherms. According to IUPAC classification [1], all three polymers are fitting type 1 physical adsorption isotherm with H3 hysteresis (except for EDA having H2 hysteresis). Moreover, TG and TGA analysis of polymers triazine-ethylenediamine (EDA) and triazine-triethylenetetramine (TETA) are provided. Due to the similarities of the structure, main decomposition temperatures are close to each other (between 593 K and 873 K). In order to understand change of FTIR spectra with adsorption and stripping Au(III), fresh, Au(III) adsorbed and recycled spectras of polymers measured. For further discussions about the effect of chain length to adsorption of Au(III) onto triazine polyamine polymer particles "Au (III) Uptake by Triazine Polyamine Polymers: Mechanism, Kinetic and Equilibrium Studies" Can et al. [2] (article in press).

  4. Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases.

    Science.gov (United States)

    Casero, Robert A; Marton, Laurence J

    2007-05-01

    The polyamines spermidine and spermine and their diamine precursor putrescine are naturally occurring, polycationic alkylamines that are essential for eukaryotic cell growth. The requirement for and the metabolism of polyamines are frequently dysregulated in cancer and other hyperproliferative diseases, thus making polyamine function and metabolism attractive targets for therapeutic intervention. Recent advances in our understanding of polyamine function, metabolic regulation, and differences between normal cells and tumour cells with respect to polyamine biology, have reinforced the interest in this target-rich pathway for drug development.

  5. Structurally Diverse Polyamines: Solid-Phase Synthesis and Interaction with DNA.

    Science.gov (United States)

    Umezawa, Naoki; Horai, Yuhei; Imamura, Yuki; Kawakubo, Makoto; Nakahira, Mariko; Kato, Nobuki; Muramatsu, Akira; Yoshikawa, Yuko; Yoshikawa, Kenichi; Higuchi, Tsunehiko

    2015-08-17

    A versatile solid-phase approach based on peptide chemistry was used to construct four classes of structurally diverse polyamines with modified backbones: linear, partially constrained, branched, and cyclic. Their effects on DNA duplex stability and structure were examined. The polyamines showed distinct activities, thus highlighting the importance of polyamine backbone structure. Interestingly, the rank order of polyamine ability for DNA compaction was different to that for their effects on circular dichroism and melting temperature, thus indicating that these polyamines have distinct effects on secondary and higher-order structures of DNA.

  6. Polyamine sensitization in offshore workers handling drilling muds.

    Science.gov (United States)

    Ormerod, A D; Wakeel, R A; Mann, T A; Main, R A; Aldridge, R D

    1989-11-01

    Oil-based mud, a complex mixture containing amines in emulsifiers, is used in offshore drilling operations. It is a skin irritant that occasionally gives rise to allergic contact sensitivity. In patch testing patients with allergy to drilling mud, we have identified polyamine (diethylenetriamine and triethylenetetramine) sensitivity in 5 patients. All 5 patients were also allergic to emulsifiers. These emulsifiers are cross-linked fatty acid amido-amines, in which unreacted amine groups are thought to cross-sensitize with these constituent polyamines. Cross-reactivity between ethylenediamine, diethylenetetramine and triethylenetetramine was found in 9 subjects.

  7. General synthesis of β-alanine-containing spider polyamine toxins and discovery of nephila polyamine toxins 1 and 8 as highly potent inhibitors of ionotropic glutamate receptors.

    Science.gov (United States)

    Lucas, Simon; Poulsen, Mette H; Nørager, Niels G; Barslund, Anne F; Bach, Tinna B; Kristensen, Anders S; Strømgaard, Kristian

    2012-11-26

    Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotropic glutamate receptor subtypes reveals that two of these, Nephila polyamine toxins 1 (NPTX-1) and 8 (NPTX-8), comprise intriguing pharmacological activities by having subnanomolar IC(50) values at kainate receptors.

  8. The effects of some polyamine biosynthetic inhibitors on growth and morphology of phytopathogenic fungi.

    Science.gov (United States)

    Rajam, M V; Galston, A W

    1985-01-01

    We have studied the effects of two polyamine biosynthetic inhibitors, alpha-difluoromethylornithine (DFMO) and alpha-difluoromethylarginine (DFMA), and of polyamines (PAs), alone and in combination, on mycelial growth and morphology of four phytopathogenic fungi: Botrytis sp, B. cinerea, Rhizoctonia solani and Monilinia fructicola. The inhibitors were added to a Czapek agar medium to get final concentrations of 0.1, 0.5 and 1.0 mM. DFMO and DFMA, suicide inhibitors of ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) respectively, inhibited mycelial growth strongly; the effect was generally more pronounced with DFMA than with DFMO, but each fungus had its own response pattern. The addition of the PAs putrescine (Put) and spermidine (Spd) to the culture medium resulted in a promotion of growth. In Botrytis sp and Monilinia fructicola exposed to inhibitors plus PAs, mycelial growth was actually increased above control values. Mycelial morphology was altered and cell size dramatically reduced in plates containing inhibitors alone, whereas with PAs alone, or in combination with inhibitors, morphology was normal, but cell length and diameters increased considerably. These results suggest that PAs are essential for growth in fungal mycelia. The inhibition caused by DFMA may be due to its arginase-mediated conversion to DFMO.

  9. Induction of phase 2 enzymes by serum oxidized polyamines through activation of Nrf2: effect of the polyamine metabolite acrolein.

    Science.gov (United States)

    Kwak, Mi-Kyoung; Kensler, Thomas W; Casero, Robert A

    2003-06-06

    The naturally occurring polycationic polyamines including putrescine, spermidine, and spermine play an important role in cell growth, differentiation, and gene expression. However, circulating polyamines are potential substrates for several oxidizing enzymes including copper-containing serum amine oxidase. These enzymes are capable of oxidizing serum polyamines to several toxic metabolites including aldehydes and H(2)O(2). In this study, we investigated the effects of polyamines as inducers of phase 2 enzymes and other genes that promote cell survival in a cell culture system in the presence of bovine serum. Spermidine and spermine (50 microM) increased NAD(P)H quinone oxidoreductase (NQO1) activity up to 3-fold in murine keratinocyte PE cells. Transcript levels for glutathione S-transferase (GST) A1, GST M1, NQO1, gamma-glutamylcysteine ligase regulatory subunit, and UDP-glucuronyltransferase 1A6 were significantly increased by spermidine and this effect was mediated through the antioxidant response element (ARE). The ARE from the mouse GST A1 promoter was activated about 9-fold by spermine and 5-fold by spermidine treatment, but could be inhibited by the amine oxidase inhibitor, aminoguanidine, suggesting that acrolein or hydrogen peroxide generated from polyamines by serum amine oxidase may be mediators for phase 2 enzyme induction. Elevations of ARE-luciferase expression and NQO1 enzyme activity by spermidine were not affected by catalase, while both were completely repressed by aldehyde dehydrogenase treatment. Direct addition of acrolein to PE cells induced multiple phase 2 genes and elevated nuclear levels of Nrf2, a transcription factor that binds to the ARE. Expression of mutant Nrf2 repressed the activation of the ARE-luciferase reporter by polyamines and acrolein. These results indicate that spermidine and spermine increase the expression of phase 2 genes in cells grown in culture through activation of the Nrf2-ARE pathway by generating the sulfhydryl

  10. Combined vitamins Bl2b and C induce the glutathione depletion and the death of epidermoid human larynx carcinoma cells HEp-2.

    Science.gov (United States)

    Akatov, V S; Evtodienko, Y V; Leshchenko, V V; Teplova, V V; Potselueva, M M; Kruglov, A G; Lezhnev, E I; Yakubovskaya, R I

    2000-10-01

    The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) can cause the death of tumor cells at the concentrations of the components at which they are nontoxic when administered separately. This cytotoxic action on epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the hydrogen peroxide generated by the combination of vitamins B12b and C. The drop in the glutathione level preceding cell death was found to be the result of combined action of the vitamins. It is supposed that the induction of cell death by combined action of vitamins B12b and C is connected to the damage of the cell redox system.

  11. Polyamine Metabolism in Flax in Response to Treatment with Pathogenic and Non-pathogenic Fusarium Strains

    Directory of Open Access Journals (Sweden)

    Wioleta eWojtasik

    2015-04-01

    Full Text Available Flax crop yield is limited by various environmental factors, but the largest crop losses worldwide are caused by Fusarium infection. Polyamines are one of the many metabolites possibly involved in the plant response to infection. However, in flax the polyamine composition, genes involved in polyamine synthesis, and their regulation, were previously unknown. The aim of this study was to investigate the polyamine synthesis pathway in flax and its involvement in response to pathogen infection. It is well established that polyamines are essential for the growth and development of both plants and fungi, but their role in pathogen infection still remains unknown. In our study we correlated the expression of genes involved in polyamine metabolism with the polyamine levels in plant tissues and compared the results for flax seedlings treated with two pathogenic and one non-pathogenic strains of Fusarium. We observed an increase in the expression of genes participating in polyamine synthesis after fungal infection, and it was reflected in an increase of polyamine content in the plant tissues. The highest level of mRNA was characteristic for ornithine decarboxylase during infection with all tested Fusarium strains and the arginine decarboxylase gene during infection with the pathogenic strain of F. culmorum. The main polyamine identified in the flax was putrescine, and its level changed the most during infection. Moreover, the considerable increase in the cell wall-bound polyamines compared to the levels of free and conjugated polyamines may indicate that their main role during pathogen infection lies in strengthening of the cell wall. In vitro experiments showed that the polyamines inhibit Fusarium growth, which suggests that they play an important role in plant defence mechanisms. Furthermore, changes in metabolism and content of polyamines indicate different defence mechanisms activated in flax in response to infection by pathogenic and non

  12. Combining the auxin-inducible degradation system with CRISPR/Cas9-based genome editing for the conditional depletion of endogenous Drosophila melanogaster proteins.

    Science.gov (United States)

    Bence, Melinda; Jankovics, Ferenc; Lukácsovich, Tamás; Erdélyi, Miklós

    2017-04-01

    Inducible protein degradation techniques have considerable advantages over classical genetic approaches, which generate loss-of-function phenotypes at the gene or mRNA level. The plant-derived auxin-inducible degradation system (AID) is a promising technique which enables the degradation of target proteins tagged with the AID motif in nonplant cells. Here, we present a detailed characterization of this method employed during the adult oogenesis of Drosophila. Furthermore, with the help of CRISPR/Cas9-based genome editing, we improve the utility of the AID system in the conditional elimination of endogenously expressed proteins. We demonstrate that the AID system induces efficient and reversible protein depletion of maternally provided proteins both in the ovary and the early embryo. Moreover, the AID system provides a fine spatiotemporal control of protein degradation and allows for the generation of different levels of protein knockdown in a well-regulated manner. These features of the AID system enable the unraveling of the discrete phenotypes of genes with highly complex functions. We utilized this system to generate a conditional loss-of-function allele which allows for the specific degradation of the Vasa protein without affecting its alternative splice variant (solo) and the vasa intronic gene (vig). With the help of this special allele, we demonstrate that dramatic decrease of Vasa protein in the vitellarium does not influence the completion of oogenesis as well as the establishment of proper anteroposterior and dorsoventral polarity in the developing oocyte. Our study suggests that both the localization and the translation of gurken mRNA in the vitellarium is independent from Vasa. © 2017 Federation of European Biochemical Societies.

  13. Global-scale assessment of groundwater depletion and related groundwater abstractions: Combining hydrological modeling with information from well observations and GRACE satellites

    Science.gov (United States)

    Döll, Petra; Müller Schmied, Hannes; Schuh, Carina; Portmann, Felix T.; Eicker, Annette

    2014-07-01

    Groundwater depletion (GWD) compromises crop production in major global agricultural areas and has negative ecological consequences. To derive GWD at the grid cell, country, and global levels, we applied a new version of the global hydrological model WaterGAP that simulates not only net groundwater abstractions and groundwater recharge from soils but also groundwater recharge from surface water bodies in dry regions. A large number of independent estimates of GWD as well as total water storage (TWS) trends determined from GRACE satellite data by three analysis centers were compared to model results. GWD and TWS trends are simulated best assuming that farmers in GWD areas irrigate at 70% of optimal water requirement. India, United States, Iran, Saudi Arabia, and China had the highest GWD rates in the first decade of the 21st century. On the Arabian Peninsula, in Libya, Egypt, Mali, Mozambique, and Mongolia, at least 30% of the abstracted groundwater was taken from nonrenewable groundwater during this time period. The rate of global GWD has likely more than doubled since the period 1960-2000. Estimated GWD of 113 km3/yr during 2000-2009, corresponding to a sea level rise of 0.31 mm/yr, is much smaller than most previous estimates. About 15% of the globally abstracted groundwater was taken from nonrenewable groundwater during this period. To monitor recent temporal dynamics of GWD and related water abstractions, GRACE data are best evaluated with a hydrological model that, like WaterGAP, simulates the impact of abstractions on water storage, but the low spatial resolution of GRACE remains a challenge.

  14. Polyamines as modulators of microcycle conidiation in Aspergillus flavus.

    Science.gov (United States)

    Khurana, N; Saxena, R K; Gupta, R; Rajam, M V

    1996-03-01

    Since polyamines (PAs) play a potential role in the regulation of growth and developmental processes in a wide variety of organisms, we have examined the influence of the PAs putrescine (Put) and spermidine (Spd) and the PA biosynthetic inhibitors alpha-difluoromethylornithine (DFMO), alpha-difluoromethylarginine (DFMA), methylglyoxal bis-(guanylhydrazone) (MGBG) and cyclohexylamine (CHA), singly and in combinations on microcycle conidiation (MC) in Aspergillus flavus. The exogenous application of the diamine Put (concentrations ranging from 0.1 to 5 mM) caused a sharp decline of MC in a dose-dependent fashion, but induced vegetative growth. However, the triamine Spd (0.1-5 mM) had a minimal effect on MC and induced a shift from MC to normal condition. PA inhibitors, especially DFMO, MGBG and CHA, produced greater inhibition of MC and complete inhibition of MC was observed at 5 mM of these inhibitors. DFMA even at 5 mM had only a weak inhibitory effect on MC. DFMO also inhibited conidial germination and germ tube growth. MGBG and CHA, while having an inhibitory effect on MC, induced vegetative growth. The inhibitory effect of PA inhibitors was partially reversed by exogenous Put or Spd, with Spd being more effective than Put. The analysis of free PA levels during various phases of MC revealed that undifferentiated spores contained a high Put/Spd ratio and there was a dramatic decrease in Put/Spd ratio before and during microcycle conidiophore maturity. The change in spermine titres could not be detected. These observations imply that Put is essential for vegetative growth, while Spd is involved in MC, and that a low Put/Spd ratio seems to be important for spore differentiation to MC.

  15. Effect of diethylstilbestrol on polyamine metabolism in hamster epididymis

    Institute of Scientific and Technical Information of China (English)

    Chun-HongQiu; MasatoOhe; ShigeruMatsuzaki

    2003-01-01

    Aim: To investigate the effect of diethylstilbestrol (DES), one of the most potent endocrine disruptors, on the metabolism of polyamines in hamster epididymis. Methods: Male golden hamsters of 7-week-old were kept under a light and dark cycle of 14 h and 10 h for 1 week to stimulate maximally the gonadal function. DES was injected subcutaneously at doses of 0.01mg·kg-1·day-1,0.1mg·kg-1·day-1 and 1mg·kg-1·day-1 for one week. Results:DES treatment caused a significant decrease in the weight of epididymis. The activity of epididymal ornithine decarboxylase (ODC) increased 1 day after DES treatment, kept at a high level for 4 days and then decreased to nearly normal level at day 7. The activity of spermidine/spermine N1-acetyltransferase (SSAT) also increased transiently after DES treatment. The contents of putrescine, spermidine, spermine and N1-acetylspermidine were increased 1 day 4 days after DES treatment and restored to normal at day 7. All these changes showed a marked difference between the caput and the cauda. Conclusion: The polyamine biosynthesis in the hamster epididymis can be affected by DES,a xenoestrogen. DES may probably affect polyamine metabolism in the epididymis by regulating the rate-limiting enzymes involved in the polyamine biosynthesis.

  16. Polyamines Inhibit Porin-Mediated Fluoroquinolone Uptake in Mycobacteria

    Science.gov (United States)

    Sarathy, Jansy Passiflora; Lee, Edmund; Dartois, Véronique

    2013-01-01

    Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. Spermidine was most effective and demonstrated reversible dose- and pH-dependent inhibition of ciprofloxacin accumulation. The extent of this inhibition was demonstrated across the fluoroquinolone compound class to varying degrees. Furthermore, we have shown that the addition of spermidine increases the survival of M. bovis BCG after a 5-day exposure to ciprofloxacin by up to 25 times. The treatment of actively-replicating Mycobacterium tuberculosis with spermidine reduced ciprofloxacin accumulation by half while non-replicating nutrient-starved M. tuberculosis cultures lacked similar sensitivity to polyamines. Gene expression studies showed that several outer membrane proteins are significantly down–regulated during the shift to non–replication. Collectively, these characteristics of fluoroquinolone uptake in M. bovis BCG are consistent with facilitated transport by porin-like proteins and suggest that a reduction in intracellular uptake contributes to the phenotypic drug resistance demonstrated by M. tuberculosis in the non-replicating state. PMID:23755283

  17. Polyamine levels and tomato fruit development: possible interaction with ethylene.

    Science.gov (United States)

    Saftner, R A; Baldi, B G

    1990-02-01

    Fruits of tomato, Lycopersicon esculentum Mill. cv Liberty, ripen slowly and have a prolonged keeping quality. Ethylene production and the levels of polyamines in pericarp of cv Liberty, Pik Red, and Rutgers were measured in relation to fruit development. Depending on the stage of fruit development, Liberty produced between 16 and 38% of the ethylene produced by Pik Red and Rutgers. The polyamines putrescine, spermidine, and spermine were present in all cultivars. Cadaverine was detected only in Rutgers. Levels of putrescine and spermidine declined between the immature and mature green stages of development and prior to the onset of climacteric ethylene production. In Pik Red and Rutgers, the decline persisted, whereas in Liberty, the putrescine level increased during ripening. Ripe pericarp of Liberty contained about three and six times more free (unconjugated) polyamines than Pik Red and Rutgers, respectively. No pronounced changes in spermidine or cadaverine occurred during ripening. The increase in the free polyamine level in ripe pericarp of Liberty may account for the reduction of climacteric ethylene production, and prolonged storage life.

  18. L-ornithine derived polyamines in cystic fibrosis airways.

    Directory of Open Access Journals (Sweden)

    Hartmut Grasemann

    Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

  19. Excretion of polyamines by children with Beckwith's syndrome.

    OpenAIRE

    Barlow, G. B.

    1980-01-01

    The urinary excretion of the polyamines--putrescine, spermidine, and spermine--was measured in 7 children with Beckwith's syndrome. Putrescine excretion was raised and spermidine excretion reduced. The raised putrescine and the low spermidine ratios were highly significant. These results are consistent with a disturbance in a metabolic pathway under growth hormone-like regulation.

  20. Do polyamines alter the sensitivity of lichens to nitrogen stress?

    Science.gov (United States)

    Pirintsos, S A; Munzi, S; Loppi, S; Kotzabasis, K

    2009-07-01

    The sensitivity of lichens measuring photosynthetic efficiency and polyamines as modulator of nitrogen stress tolerance was investigated. Two lichen species with a markedly different tolerance to nitrogen compounds, namely Evernia prunastri (L.) Ach. and Xanthoria parietina (L.) Th.Fr., were incubated with deionized water (control) and solutions of KNO(3), NH(4)NO(3) and (NH(4))(2)SO(4) and then exposed to different light conditions. The F(v)/F(m) parameter (maximum quantum efficiency of photosystem II) was used as stress indicator. The results showed that F(v)/F(m) values, in the produced experimental conditions, were independent from the light gradient. Photosynthetic efficiency of E. prunastri was impaired by high ammonium concentrations, while nitrate had no effect; X. parietina was hardly influenced by nitrogen compounds. External supply of polyamines reduced the sensitivity of E. prunastri, while polyamine inhibitors reduced the tolerance of X. parietina to NH(4)(+), suggesting that polyamines play an important role in modulating the sensitivity/tolerance to nitrogen stress.

  1. Structural identification of long-chain polyamines associated with diatom biosilica in a Southern Ocean sediment core

    Science.gov (United States)

    Bridoux, Maxime C.; Ingalls, Anitra E.

    2010-07-01

    Long-chain polyamines (LCPAs) constitute a new family of natural organic compounds that have recently been isolated and characterized from the biosilicified cell walls of diatom cultures. To date, diatom-specific polyamines have not been investigated from the marine environment and their fate in the environment is entirely unknown. Here, we report a series of LCPAs in a diatom frustule-rich sediment core (TNO57-13 PC4), originating from the Atlantic sector of the Southern Ocean and spanning from the Holocene to the Last Glacial Maximum (LGM). Liquid chromatography with electrospray ionization mass spectrometry (LC-ESI-MS) revealed a complex mixture of linear polyamines with at least 28 individual molecular species. Ion trap mass fragmentation studies, combined with high resolution Time of Flight (TOF) mass spectrometry showed that the polyamine pool consisted of a series of N-methylated propylamine compounds attached to a putrescine moiety, with individual LCPAs varying in chain length and degree of methylation. The structural similarity between LCPAs extracted from the diatom-rich sediment core and those extracted from the frustules of cultured diatoms suggests that sedimentary LCPAs are derived from diatom frustules. We hypothesize that these intrinsically labile organic molecular fossils are protected from diagenesis by encapsulation within the frustule. These compounds constitute a new class of biomarkers that could potentially be indicators of diatom species distribution. Isotopic analysis of LCPAs could be used to improve age models for sediment cores that lack calcium carbonate and to improve current interpretations of diatom-based paleoproxies, including diatom-bound nitrogen isotopes.

  2. Design and fabrication of branched polyamine functionalized mesoporous silica: an efficient absorbent for water remediation.

    Science.gov (United States)

    Nayab, Sana; Farrukh, Aleeza; Oluz, Zehra; Tuncel, Eylül; Tariq, Saadia Rashid; ur Rahman, Habib; Kirchhoff, Katrin; Duran, Hatice; Yameen, Basit

    2014-03-26

    A novel branched polyamine (polyethyleneimine, PEI) functionalized mesoporous silica (MS) adsorbent is developed via a facile "grafting-to" approach. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy verified the effective surface functionalization of MS with monolayer and polymer. The transmission electron microscopy (TEM) was employed to reveal the morphology of the fabricated materials. The adsorption behavior of the polyamine functionalized mesoporous silica (MS-PEI) is assessed against anionic dyes. The adsorbent characteristics of MS-PEI are compared with a monolayer platform comprising of 3-aminopropyltriethoxy silane (APTES) functionalized mesoporous silica (MS-APTES). The adsorption behavior of the MS-PEI and MS-APTES toward anionic dyes is further evaluated by studying the effect of adsorbent dosage, pH, contact time, and temperature. Langmuir and Freundlich isotherm models are employed to understand the adsorption mechanism. The obtained kinetic data support a pseudo-second-order adsorption behavior for both monolayer and polymer functionalized MS. The associated thermodynamic parameters (ΔG°, ΔH°, and ΔS°) reveal that the process of adsorption with MS-PEI is more spontaneous and energetically favored as compared to the adsorption with MS-APTES. Taken together, the novel adsorbent system derived from a combination of MS and branched polymer (MS-PEI) shows the higher absorption efficiency and capacity toward the anionic dyes than the monolayer based adsorbent (MS-APTES).

  3. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

      The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...... giving rise to depletion layers, and the mechanisms and border conditions that control their presence and extension require still clarification. Recently, careful systematic reflectivity experiments were re-done on the same system. No depletion layers were found, and it was conjectured that the whole...

  4. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    Science.gov (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  5. Addressing Ozone Layer Depletion

    Science.gov (United States)

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  6. Levels of Polyamines and Kinetic Characterization of Their Uptake in the Soybean Pathogen Phytophthora sojae

    OpenAIRE

    Chibucos, M. Constantine; Paul F Morris

    2006-01-01

    Polyamines are ubiquitous biologically active aliphatic cations that are at least transiently available in the soil from decaying organic matter. Our objectives in this study were to characterize polyamine uptake kinetics in Phytophthora sojae zoospores and to quantify endogenous polyamines in hyphae, zoospores, and soybean roots. Zoospores contained 10 times more free putrescine than spermidine, while hyphae contained only 4 times as much free putrescine as spermidine. Zoospores contained no...

  7. Conjugation of biogenic and synthetic polyamines with serum proteins: A comprehensive review.

    Science.gov (United States)

    Chanphai, P; Thomas, T J; Tajmir-Riahi, H A

    2016-11-01

    We have reviewed the conjugation of biogenic polyamines spermine (spm), spermidine (spmd) and synthetic polyamines 3,7,11,15-tetrazaheptadecane.4HCl (BE-333) and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333) with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. The results of multiple spectroscopic methods and molecular modeling were analysed here and correlations between polyamine binding mode and protein structural changes were estabilished. Polyamine-protein bindings are mainly via hydrophilic and H-bonding contacts. BSA forms more stable conjugates than HSA and b-LG. Biogenic polyamines form more stable complexes than synthetic polyamines except in the case of b-LG, where the protein shows more hydrophobic character than HSA and BSA. The loading efficacies were 40-52%. Modeling showed the presence of several H-bonding systems, which stabilized polyamine-protein conjugates. Polyamine conjugation induced major alterations of serum protein conformations. The potential application of serum proteins in delivery of polyamines is evaluated here.

  8. Abnormal urinary excretion of polyamines in HHH syndrome (hyperornithinemia associated with hyperammonemia and homocitrullinuria).

    Science.gov (United States)

    Shimizu, H; Maekawa, K; Eto, Y

    1990-01-01

    The HHH syndrome (hyperornithinemia associated with hyperammonemia and homocitrullinuria) is characterized by a very rare genetic defect of ornithine transport in mitochondrial membrane. We first demonstrated that a patient with HHH syndrome excreted about 6 times higher amount of polyamines in urine than the control when supplemented with high protein diets and ornithine loading. Each urinary polyamine fraction measured by HPLC method in HHH syndrome appears to be increased, as compared with those of the control. These data suggest that increased urinary excretion of polyamines in this syndrome is closely related to overflowing of plasma polyamine due to an ornithine transport defect in the mitochondrial membrane.

  9. Characterization of a Polyamine Microsphere and Its Adsorption for Protein

    Directory of Open Access Journals (Sweden)

    Huixian Wei

    2012-12-01

    Full Text Available A novel polyamine microsphere, prepared from the water-in-oil emulsion of polyethylenimine, was characterized. The investigation of scanning electron microscopy showed that the polyamine microsphere is a regular ball with a smooth surface. The diameter distribution of the microsphere is 0.37–4.29 μm. The isoelectric point of the microsphere is 10.6. The microsphere can adsorb proteins through the co-effect of electrostatic and hydrophobic interactions. Among the proteins tested, the highest value of adsorption of microsphere, 127.8 mg·g−1 microsphere, was obtained with lipase. In comparison with other proteins, the hydrophobic force is more important in promoting the adsorption of lipase. The microsphere can preferentially adsorb lipase from an even mixture of proteins. The optimum temperature and pH for the selective adsorption of lipase by the microsphere was 35 °C and pH 7.0.

  10. Ozone Depletion from Nearby Supernovae

    CERN Document Server

    Gehrels, N; Jackman, C H; Cannizzo, J K; Mattson, B J; Chen, W; Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan

    2003-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time, improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made in theoretical modeling of supernovae and of the resultant gamma-ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma-rays and cosmic rays. We find that for the combined ozone depletion roughly to double the ``biologically active'' UV flux received at the surface of the Earth, the supernova mu...

  11. Ozone Depletion from Nearby Supernovae

    Science.gov (United States)

    Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made also in theoretical modeling of supernovae and of the resultant gamma ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma rays and cosmic rays. We find that for the combined ozone depletion from these effects roughly to double the 'biologically active' UV flux received at the surface of the Earth, the supernova must occur at approximately or less than 8 parsecs.

  12. Cardioprotection and lifespan extension by the natural polyamine spermidine

    OpenAIRE

    Eisenberg, Tobias; Abdellatif, Mahmoud; Schroeder, Sabrina; Primessnig, Uwe; Stekovic, Slaven; Pendl, Tobias; Harger, Alexandra; Schipke, Julia; Zimmermann, Andreas; SCHMIDT, Albrecht; Tong, Mingming; Ruckenstuhl, Christoph; Dammbrueck, Christopher; Gross, Angelina S; Herbst, Viktoria

    2016-01-01

    Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin...

  13. Polyamine-Induced Rapid Root Abscission in Azolla pinnata

    OpenAIRE

    Sushma Gurung; Cohen, Michael F.; Jon Fukuto; Hideo Yamasaki

    2012-01-01

    Floating ferns of the genus Azolla detach their roots under stress conditions, a unique adaptive response termed rapid root abscission. We found that Azolla pinnata plants exhibited dose-dependent rapid root abscission in response to the polyamines spermidine and spermine after a substantial time lag (>20 min). The duration of the time lag decreased in response to high pH and high temperature whereas high light intensity increased the time lag and markedly lowered the rate of abscission. The ...

  14. Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

    Science.gov (United States)

    Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

    2015-10-01

    The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.

  15. Polyamines in relation to growth in carrot cell cultures.

    Science.gov (United States)

    Fallon, K M; Phillips, R

    1988-09-01

    Changes in polyamine metabolism were investigated in relation to growth of cell suspension cultures of carrot (Daucus carota, cv Chantenay). Changes in levels of the major amines putrescine and spermidine throughout the culture period correlated poorly with changes in fresh weight, but a closer correlation with the minor component spermine was observed. The arginine decarboxylase (ADC) inhibitor difluoromethylarginine (DFMA) strongly and specifically inhibited ADC activity in the supernatant, reduced the major amine (putrescine) by 95% and the total amine content by 80%. It had no effect on cell number and stimulated fresh weight by over 25% through increased cell expansion. Spermine content, in contrast, increased with DFMA concentration in parallel with fresh weight increases. Difluoromethylornithine strongly inhibited ornithine decarboxylase activity in the pellet, but had little effect on either polyamine levels or culture growth. It was concluded that little evidence for a correlation between free polyamines and cell number in carrot cultures could be detected, but that a possible correlation between spermine content and cell expansion was observed.

  16. Polyamines in Relation to Growth in Carrot Cell Cultures 1

    Science.gov (United States)

    Fallon, Kevin M.; Phillips, Richard

    1988-01-01

    Changes in polyamine metabolism were investigated in relation to growth of cell suspension cultures of carrot (Daucus carota, cv Chantenay). Changes in levels of the major amines putrescine and spermidine throughout the culture period correlated poorly with changes in fresh weight, but a closer correlation with the minor component spermine was observed. The arginine decarboxylase (ADC) inhibitor difluoromethylarginine (DFMA) strongly and specifically inhibited ADC activity in the supernatant, reduced the major amine (putrescine) by 95% and the total amine content by 80%. It had no effect on cell number and stimulated fresh weight by over 25% through increased cell expansion. Spermine content, in contrast, increased with DFMA concentration in parallel with fresh weight increases. Difluoromethylornithine strongly inhibited ornithine decarboxylase activity in the pellet, but had little effect on either polyamine levels or culture growth. It was concluded that little evidence for a correlation between free polyamines and cell number in carrot cultures could be detected, but that a possible correlation between spermine content and cell expansion was observed. PMID:16666271

  17. Plasticizing Effects of Polyamines in Protein-Based Films

    Directory of Open Access Journals (Sweden)

    Mohammed Sabbah

    2017-05-01

    Full Text Available Zeta potential and nanoparticle size were determined on film forming solutions of native and heat-denatured proteins of bitter vetch as a function of pH and of different concentrations of the polyamines spermidine and spermine, both in the absence and presence of the plasticizer glycerol. Our results showed that both polyamines decreased the negative zeta potential of all samples under pH 8.0 as a consequence of their ionic interaction with proteins. At the same time, they enhanced the dimension of nanoparticles under pH 8.0 as a result of macromolecular aggregations. By using native protein solutions, handleable films were obtained only from samples containing either a minimum of 33 mM glycerol or 4 mM spermidine, or both compounds together at lower glycerol concentrations. However, 2 mM spermidine was sufficient to obtain handleable film by using heat-treated samples without glycerol. Conversely, brittle materials were obtained by spermine alone, thus indicating that only spermidine was able to act as an ionic plasticizer. Lastly, both polyamines, mainly spermine, were found able to act as “glycerol-like” plasticizers at concentrations higher than 5 mM under experimental conditions at which their amino groups are undissociated. Our findings open new perspectives in obtaining protein-based films by using aliphatic polycations as components.

  18. INVESTIGATION OF POLYAMINE METABOLISM BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC AND GAS-CHROMATOGRAPHIC PROFILING METHODS

    NARCIS (Netherlands)

    MUSKIET, FAJ; DORHOUT, B; VANDENBERG, GA; HESSELS, J

    1995-01-01

    Measurements of polyamines, polyamine conjugates and their metabolites in tissues, cells and extracellular fluids are used in biochemistry, (micro)biology, oncology and parasitology. Decarboxylation of ornithine yields putrescine. Aminopropylation of putrescine yields spermidine, and aminopropylatio

  19. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2).    The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  20. Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na+ channels.

    Science.gov (United States)

    Fleidervish, Ilya A; Libman, Lior; Katz, Efrat; Gutnick, Michael J

    2008-12-02

    Because the excitable properties of neurons in the neocortex depend on the characteristics of voltage-gated Na(+) channels, factors which regulate those characteristics can fundamentally modify the dynamics of cortical circuits. Here, we report on a novel neuromodulatory mechanism that links the availability of Na(+) channels to metabolism of polyamines (PAs) in the cerebral cortex. Using single channel and whole-cell recordings, we found that products of PA metabolism, the ubiquitous aliphatic polycations spermine and spermidine, are endogenous blockers of Na(+) channels in layer 5 pyramidal cells. Because the blockade is activity-dependent, it is particularly effective against Na(+) channels which fail to inactivate rapidly and thus underlie the persistent Na(+) current. At the level of the local cortical circuit, pharmacological depletion of PAs led to increased spontaneous spiking and periods of hypersynchronous discharge. Our data suggest that changes in PA levels, whether associated with normal brain states or pathological conditions, profoundly modify Na(+) channel availability and thereby shape the integrative behavior of single neurons and neocortical circuits.

  1. Shear-affected depletion interaction

    NARCIS (Netherlands)

    July, C.; Kleshchanok, D.; Lang, P.R.

    2012-01-01

    We investigate the influence of flow fields on the strength of the depletion interaction caused by disc-shaped depletants. At low mass concentration of discs, it is possible to continuously decrease the depth of the depletion potential by increasing the applied shear rate until the depletion force i

  2. Interfacial polymerization of cyanuric chloride and monomeric amines: pH resistant thin film composite polyamine nanofiltration membranes

    NARCIS (Netherlands)

    Lee, Kah P.; Bargeman, Gerrald; Rooij, de Ralph; Kemperman, Antoine J.B.; Benes, Nieck E.

    2017-01-01

    Polyamine nanofiltration membranes have a high stability at extreme pH conditions. In contrast to polyamides, polyamines do not contain the carbonyl group that is susceptible to nucleophilic attack. A previous study has shown that polyamine membranes can be prepared from the interfacial polymerizati

  3. A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

    NARCIS (Netherlands)

    Paridaens, R; Uges, DRA; Barbet, N; Choi, L; Seeghers, M; van der Graaf, WTA; Groen, HJM; Dumez, H; Van Buuren, [No Value; Muskiet, F; Capdeville, R; van Oosterom, AT; de Vries, EGE

    2000-01-01

    Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionin

  4. Molecular evolution of the polyamine oxidase gene family in Metazoa

    Directory of Open Access Journals (Sweden)

    Polticelli Fabio

    2012-06-01

    Full Text Available Abstract Background Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO and acetylpolyamine oxidase (APAO, specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO, it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. Results We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported

  5. IN-VIVO EFFECTS OF 4-AMIDINOINDAN-1-ONE 2'-AMIDINOHYDRAZONE (CGP 48664A) AND ALPHA-DIFLUOROMETHYLORNITHINE (DFMO) ON L1210 GROWTH, CELL-CYCLE PHASE DISTRIBUTION AND POLYAMINE CONTENTS

    NARCIS (Netherlands)

    DORHOUT, B; TEVELDE, RJ; FERWERDA, H; KINGMA, AW; DEHOOG, E; MUSKIET, FAJ

    1995-01-01

    We studied the in vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), alpha-difluoromethylornithine (DFMO) and a combination of CGP 48654A-DFMO on tumor growth, cell-cycle phase distribution and polyamine contents. DBA-2, mice were inoculated i.p. with 10(5) L1210 cells on day 0,

  6. 40 CFR 721.6440 - Polyamine urea-for-malde-hyde condensate (specific name).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyamine urea-for-malde-hyde condensate (specific name). 721.6440 Section 721.6440 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.6440 Polyamine urea-for-malde-hyde condensate...

  7. Production of Polyamines Is Enhanced by Endogenous Abscisic Acid in Maize Seedlings Subjected to Salt Stress

    Institute of Scientific and Technical Information of China (English)

    Jun LIU; Ming-Yi JIANG; Yi-Feng ZHOU; You-Liang LIU

    2005-01-01

    It is known that salt stress and exogenously applied abscisic acid (ABA) can enhance the polyamine content in plants and that salt stress itself can lead to an increase in endogenous ABA production.In the present study, the relationships between salt-induced ABA and polyamine accumulation were investigated using ABA-deficient mutant (vp5/vp5) maize (Zea mays L.) seedlings and ABA and polyamine :biosynthesis inhibitors. The results show that reduced endogenous ABA levels, as a result of either the mutation or by using a chemical inhibitor (sodium tungstate), also reduced the accumulation of polyamines in salt-stressed leaves of maize seedlings. The polyamine synthesis inhibitors D-arginine and αdifluoromethylornithine also reduced the polyamine content of the leaves of maize seedling under salt stress. Both ABA and polyamine enhanced the dry weight accumulation of salt-stressed seedlings and also increased the activities of the two dominant tonoplast membrane enzymes, H+-ATPase and H+-PPase, when plants were under salt stress. The results suggest that salt stress induces an increase in endogenous ABA levels, which then enhances polyamine synthesis. Such responses may increase a plant's tolerance to salt.

  8. [Effect of polysaccharides from Radix Glycyrrhizae on migration and polyamines contents of IEC-6 cell].

    Science.gov (United States)

    Wen, Peng; Sui, Jing-Jing; Li, Ru-Liu; Zhao, Shi-Qing; Lu, Wen-Biao; Chen, Wei-Wen

    2012-07-01

    To study the effect of polysaccharides from Radix Glycyrrhizae on migration and polyamines (putrescine, spermidine and spermine) contents of IEC-6 cell. Cell migration model was induced by scratch method in each well,and the polyamines in IEC-6 cell was determined by pre-column derivation high performance liquid chromatography. The polysaccharides inhibited effect on migration and polyamines contents of IEC-6 cells, and on IEC-6 cell migration by DFMO (a polyamines synthesis inhibitor) and the polyamines contents in the cells were observed. The polysaccharides (50 mg/L or 100 mg/L) was able to promote the cell migration, reverse the cell migration inhibition by DFMO, enhance the IEC-6 cell polyamines (putrescine, spermidine and spermine) contents in the process of cell migration and reverse the reduction of polyamines (putrescine, spermidine and spermine) induced by DFMO. The effect of Radix Glycyrrhizae on the gastrointestinal mucosal damage repairing may be related to increasing polyamine content in cells and promoting cell migration.

  9. Role of Polyamine Oxidase (PAOh1/SMO) in Human Breast Cancer

    Science.gov (United States)

    2006-04-01

    Page 3 INTRODUCTION The natural polyamines, spermine, spermidine, and their diamine precursor, putrescine , are ubiquitous polycationic bases...spermidine, and putrescine upon BENSpm treatment with a similar level of BENSpm accumulation in each cell line (Table 1). BENSpm treatment also reduced ODC...for ODC enzyme activity. Polyamines (nmol/mg protein) BENSpm ODC Activity Cell line Treatment Putrescine Spermidine Spermine (nmol/mg

  10. Regulation of polyamine synthesis in plants. Final progress report, July 1, 1991--December 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Malmberg, R.L.

    1995-07-01

    This research focused on unusual post-translational modifications occuring in a arginine decarboxylase cDNA clone in oats. A novel regulatory mechanism for polyamines was explored and an attempt was made to characterize it. A plant ornithine decarboxylase cDNA was identified in Arabidopsis. Further work remains on the mechanisms of polyamine regulation and function in plants.

  11. Structure–Activity Relationship Study of Spider Polyamine Toxins as Inhibitors of Ionotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Poulsen, Mette H; Hussein, Rama A

    2014-01-01

    The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only...

  12. Synthesis and biological evaluation of hydrazino-containing polyamine skeletons as drug delivery system

    Institute of Scientific and Technical Information of China (English)

    Jian Hong Wang; Jun Jun Zhou; Song Qing Xie; Qian Li; Jin Zhao; Chao Jie Wang

    2011-01-01

    A new series of polyamine-toxic cargo conjugates was synthesized with aryl aldehydes conjugating to hydrazino-containing triamine skeletons.The in vitro cytotoxicity of target compounds was evaluated in several cancer cell lines (e.g.,L1210,HeLa and B16) and the cellular entry of these polyamine conjugates via polyamine transporter was investigated on SPD- or DFMO-treated B16 cell line.Of these compounds,6c show significant cytotoxicity on L1210,HeLa and B 16 cell lines (ICs0 value,3.74 μmol/L,5.66 μmol/L and 4.04 μmol/L,respectively).The polyamine transporter assay demonstrated the suitability of hydrazino-containing polyamine backbones for application as vectors in drug delivery systems.

  13. Depletion of intense fields

    CERN Document Server

    Seipt, D; Marklund, M; Bulanov, S S

    2016-01-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multi-photon Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multi-photon nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude $a_0 \\sim 10^3$ and electron bunches with charges of the order of nC.

  14. Depletion of Intense Fields

    Science.gov (United States)

    Seipt, D.; Heinzl, T.; Marklund, M.; Bulanov, S. S.

    2017-04-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multiphoton Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multiphoton nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude a0˜1 03 and electron bunches with charges of the order of 10 nC.

  15. Liquid chromatography method to determine polyamines in thermosetting polymers

    Energy Technology Data Exchange (ETDEWEB)

    Dopico-Garcia, M.S. [Laboratorio de Quimica - Centro de Investigacions Tecnoloxicas, Universidade da Coruna, Campus de Esteiro s/n, 15403 Ferrol (Spain); Centro Galego do Plastico, A Cabana s/n, 15590 Ferrol (Spain); Lopez-Vilarino, J.M. [Laboratorio de Quimica - Centro de Investigacions Tecnoloxicas, Universidade da Coruna, Campus de Esteiro s/n, 15403 Ferrol (Spain); Fernandez-Martinez, G. [Unidad de Tecnicas Cromatograficas, Servizos de Apoio a Investigacion, Edificio Servizos Centrais de Investigacion, Universidade da Coruna, Campus de Elvina s/n, 15071 A Coruna (Spain); Gonzalez-Rodriguez, M.V., E-mail: victoria@udc.es [Dpto. de Quimica Analitica - E.U. Politecnica, Universidade da Coruna, Avda. 19 de Febrero s/n, 15405 Ferrol (Spain)

    2010-05-14

    A simple, robust and sensitive analytical method to determine three polyamines commonly used as hardeners in epoxy resin systems and in the manufacture of polyurethane is reported. The studied polyamines are: one tetramine, TETA (triethylenetetramine), and two diamines, IPDA (Isophorone diamine) and TCD-diamine (4,7-methano-1H-indene-5,?-dimethanamine, octahydro-). The latter has an incompletely defined structure, and, as far as we know, has not been previously determined by other methods. All three polyamines contain primary amines; TETA also contains secondary amines. The analytical method involves derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, used for the first time for these compounds, followed by high performance liquid chromatography (HPLC) analysis with a fluorescence (FL) detector ({lambda} excitation 248 nm, {lambda} emision 395 nm). The HPLC-DAD-LTQ Orbitrap MS was used in order to provide structural information about the obtained derivatized compounds. The hybrid linear ion trap LTQ Orbitrap mass spectrometer has been introduced in recent years and provides a high mass accuracy. The structures of the derivatized analytes were identified from the protonated molecular ions [M+H]{sup +} and corresponded to the fully labelled analytes. The following analytical parameters were determined for the method using the HPLC-FL: linearity, precision (2.5-10%), instrumental precision intraday (0.8-1.5%) and interday (2.9-6.3%), and detection limits (0.02-0.14 mg L{sup -1}). The stability of stock solutions and derivatized compounds was also investigated. The method was applied to determine the amine free content in epoxy resin dust collected in workplaces.

  16. Comparison of soybean cultivars for enhancement of the polyamine contents in the fermented soybean natto using Bacillus subtilis (natto).

    Science.gov (United States)

    Kobayashi, Kazuya; Horii, Yuichiro; Watanabe, Satoshi; Kubo, Yuji; Koguchi, Kumiko; Hoshi, Yoshihiro; Matsumoto, Ken-Ichi; Soda, Kuniyasu

    2017-03-01

    Polyamines have beneficial properties to prevent aging-associated diseases. Raw soybean has relatively high polyamine contents; and the fermented soybean natto is a good source of polyamines. However, detailed information of diversity of polyamine content in raw soybean is lacking. The objectives of this study were to evaluate differences of polyamines among raw soybeans and select the high polyamine-containing cultivar for natto production. Polyamine contents were measured chromatographically in 16 samples of soybean, which showed high variation among soybeans as follows: 93-861 nmol/g putrescine, 1055-2306 nmol/g spermidine, and 177-578 nmol/g spermine. We then confirmed the high correlations of polyamine contents between raw soybean and natto (r = 0.96, 0.95, and 0.94 for putrescine, spermidine, and spermine, respectively). Furthermore, comparison of the polyamine contents among 9 Japanese cultivars showed that 'Nakasen-nari' has the highest polyamine contents, suggesting its suitability for enhancement of polyamine contents of natto.

  17. Polyamines Are Required for Virulence in Salmonella enterica Serovar Typhimurium

    DEFF Research Database (Denmark)

    Jelsbak, Lotte; Thomsen, Line Elnif; Wallrodt, Inke;

    2012-01-01

    for studying typhoid fever. Central to its virulence are two major virulence loci Salmonella Pathogenicity Island 1 and 2 (SPI1 and SPI2). SPI1 promotes invasion of epithelial cells, whereas SPI2 enables S. Typhimurium to survive and proliferate within specialized compartments inside host cells. In this study......, we show that an S. Typhimurium polyamine mutant is defective for invasion, intracellular survival, killing of the nematode Caenorhabditis elegans and systemic infection of the mouse model of typhoid fever. Virulence of the mutant could be restored by genetic complementation, and invasion...

  18. Polyamines: total daily intake in adolescents compared to the intake estimated from the Swedish Nutrition Recommendations Objectified (SNO

    Directory of Open Access Journals (Sweden)

    Mohamed Atiya Ali

    2011-01-01

    Full Text Available Background: Dietary polyamines have been shown to give a significant contribution to the body pool of polyamines. Knowing the levels of polyamines (putrescine, spermidine, and spermine in different foods and the contribution of daily food choice to polyamine intake is of interest, due to the association of these bioactive amines to health and disease. Objective: To estimate polyamine intake and food contribution to this intake in adolescents compared to a diet fulfilling the Swedish Nutrition Recommendations. Design: A cross-sectional study of dietary intake in adolescents and an ‘ideal diet’ (Swedish nutrition recommendations objectified [SNO] list of foods was used to compute polyamine intake using a database of polyamine contents of foods. For polyamine intake estimation, 7-day weighed food records collected from 93 adolescents were entered into dietetic software (Dietist XP including data on polyamine contents of foods. The content of polyamines in foods recommended according to SNO was entered in the same way. Results: The adolescents’ mean daily polyamine intake was 316±170 µmol/day, while the calculated contribution according to SNO was considerably higher with an average polyamine intake of 541 µmol/day. In both adolescent's intake and SNO, fruits contributed to almost half of the total polyamine intake. The reason why the intake among the adolescents was lower than the one calculated from SNO was mainly due to the low vegetable consumption in the adolescents group. Conclusions: The average daily total polyamine intake was similar to that previously reported in Europe. With an ‘ideal’ diet according to Swedish nutrition recommendations, the intake of this bioactive non-nutrient would be higher than that reported by our adolescents and also higher than that previously reported from Europe.

  19. Ozone-depleting Substances (ODS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global warming...

  20. Arabidopsis thaliana polyamine content is modified by the interaction with different Trichoderma species.

    Science.gov (United States)

    Salazar-Badillo, Fatima Berenice; Sánchez-Rangel, Diana; Becerra-Flora, Alicia; López-Gómez, Miguel; Nieto-Jacobo, Fernanda; Mendoza-Mendoza, Artemio; Jiménez-Bremont, Juan Francisco

    2015-10-01

    Plants are associated with a wide range of microorganisms throughout their life cycle, and some interactions result on plant benefits. Trichoderma species are plant beneficial fungi that enhance plant growth and development, contribute to plant nutrition and induce defense responses. Nevertheless, the molecules involved in these beneficial effects still need to be identify. Polyamines are ubiquitous molecules implicated in plant growth and development, and in the establishment of plant microbe interactions. In this study, we assessed the polyamine profile in Arabidopsis plants during the interaction with Trichoderma virens and Trichoderma atroviride, using a system that allows direct plant-fungal contact or avoids their physical interaction (split system). The plantlets that grew in the split system exhibited higher biomass than the ones in direct contact with Trichoderma species. After 3 days of interaction, a significant decrease in Arabidopsis polyamine levels was observed in both systems (direct contact and split). After 5 days of interaction polyamine levels were increased. The highest levels were observed with T. atroviride (split system), and with T. virens (direct contact). The expression levels of Arabidopsis ADC1 and ADC2 genes during the interaction with the fungi were also assessed. We observed a time dependent regulation of ADC1 and ADC2 genes, which correlates with polyamine levels. Our data show an evident change in polyamine profile during Arabidopsis - Trichoderma interaction, accompanied by evident alterations in plant root architecture. Polyamines could be involved in the changes undergone by plant during the interaction with this beneficial fungus.

  1. Polyamine biosynthesis is critical for growth and differentiation of the pancreas

    Science.gov (United States)

    Mastracci, Teresa L.; Robertson, Morgan A.; Mirmira, Raghavendra G.; Anderson, Ryan M.

    2015-01-01

    The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. Moreover, we demonstrate that inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine synthase (DHS). These data identify that the pancreatic requirement for polyamine biosynthesis is largely mediated through a requirement for spermidine for the downstream posttranslational modification of eIF5A by its enzymatic activator DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role for polyamine biosynthesis in pancreatic organogenesis and identified that it may be possible to exploit polyamine biosynthesis to manipulate pancreatic cell differentiation. PMID:26299433

  2. Polyamine biosynthesis is critical for growth and differentiation of the pancreas.

    Science.gov (United States)

    Mastracci, Teresa L; Robertson, Morgan A; Mirmira, Raghavendra G; Anderson, Ryan M

    2015-08-24

    The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. Moreover, we demonstrate that inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine synthase (DHS). These data identify that the pancreatic requirement for polyamine biosynthesis is largely mediated through a requirement for spermidine for the downstream posttranslational modification of eIF5A by its enzymatic activator DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role for polyamine biosynthesis in pancreatic organogenesis and identified that it may be possible to exploit polyamine biosynthesis to manipulate pancreatic cell differentiation.

  3. AGP2 encodes the major permease for high affinity polyamine import in Saccharomyces cerevisiae.

    Science.gov (United States)

    Aouida, Mustapha; Leduc, Anick; Poulin, Richard; Ramotar, Dindial

    2005-06-24

    Polyamines play essential functions in many aspects of cell biology. Plasma membrane transport systems for the specific uptake of polyamines exist in most eukaryotic cells but have been very recently identified at the molecular level only in the parasite Leishmania. We now report that the high affinity polyamine permease in Saccharomyces cerevisiae is identical to Agp2p, a member of the yeast amino acid transporter family that was previously identified as a carnitine transporter. Deletion of AGP2 dramatically reduces the initial velocity of spermidine and putrescine uptake and confers strong resistance to the toxicity of exogenous polyamines, and transformation with an AGP2 expression vector restored polyamine transport in agp2delta mutants. Yeast mutants deficient in polyamine biosynthesis required >10-fold higher concentrations of exogenous putrescine to restore cell proliferation upon deletion of the AGP2 gene. Disruption of END3, a gene required for an early step of endocytosis, increased the abundance of Agp2p, an effect that was paralleled by a marked up-regulation of spermidine transport velocity. Thus, AGP2 encodes the first eukaryotic permease that preferentially uses spermidine over putrescine as a high affinity substrate and plays a central role in the uptake of polyamines in yeast.

  4. Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.

    Science.gov (United States)

    Lewis, John R; O'Brien, Thomas G; Skorupski, Katherine A; Krick, Erika L; Reiter, Alexander M; Jennings, Michael W; Jurney, Carrie H; Shofer, F S

    2013-01-01

    This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.

  5. Polyamines are essential for virulence in Salmonella enterica serovar Gallinarum despite evolutionary decay of polyamine biosynthesis genes

    DEFF Research Database (Denmark)

    Schroll, Casper; Christensen, Jens P.; Christensen, Henrik

    2014-01-01

    to spermidine, were attenuated. In contrast, speB was dispensable after intraperitoneal challenge, suggesting that putrescine was less important for the systemic phase of the disease. In support of this hypothesis, a ΔspeE;ΔpotCD mutant, unable to synthesize and import spermidine, but with retained ability...... to import and synthesize putrescine, was attenuated after intraperitoneal infection. We therefore conclude that polyamines are essential for virulence of S. Gallinarum. Furthermore, our results point to distinct roles for putrescine and spermidine during systemic infection....

  6. Developmental changes in polyamines and autophagic marker levels in normal and growth-restricted fetal pigs.

    Science.gov (United States)

    Zhu, Y H; Lin, G; Dai, Z L; Zhou, T J; Yuan, T L; Feng, C P; Chen, F; Wu, G Y; Wang, J J

    2015-07-01

    Polyamines are essential for embryonic and fetal survival, growth, and development. Additionally, polyamines may induce autophagy in mammalian cells. However, little is known about the availability of polyamines or autophagy in the porcine conceptus with intrauterine growth restriction (IUGR). The present study was performed to evaluate the developmental changes of polyamine concentrations in IUGR and normal porcine fetuses as well as autophagic marker levels in the fetal intestinal mucosa during the second half of gestation when most fetal growth occurs. Allantoic fluid (ALF), amniotic fluid (AMF), umbilical vein, and the small-intestinal mucosa were obtained from both IUGR and normal fetal pigs at d 60, 90, and 110 of gestation. Concentrations of polyamines in fetal fluids as well as protein abundances of microtubule-associated protein light chain 3B (LC3B), an autophagic marker, in the fetal small-intestinal mucosa were determined. Concentrations of polyamines varied greatly in different fetal compartments and changed substantially with advancing gestation. Concentrations of polyamines in IUGR fetal fluids and the small-intestinal mucosa were markedly different from those in their normal counterparts at d 60 and 90 of gestation, whereas most of the differences were not detected by late (d 110) gestation. Specifically, polyamine levels were lower in the umbilical vein plasma but higher in ALF and AMF from IUGR fetuses. Furthermore, enhanced levels of an autophagic marker were observed in the small-intestinal mucosa of IUGR fetuses throughout mid and late gestation in association with abnormal spermidine levels in fetal plasma. These findings support the notion that enhanced autophagy may be an important survival mechanism in IUGR fetuses. Collectively, our findings provide a new framework for future studies to define the roles for polyamines in the prevention and treatment of IUGR in both human medicine and animal production.

  7. Recent Advances in Polyamine Metabolism and Abiotic Stress Tolerance

    Directory of Open Access Journals (Sweden)

    Parimalan Rangan

    2014-01-01

    Full Text Available Global warming is an alarming problem in agriculture and its effect on yield loss has been estimated to be five per cent for every degree centigrade rise in temperature. Plants exhibit multiple mechanisms like optimizing signaling pathway, involvement of secondary messengers, production of biomolecules specifically in response to stress, modulation of various metabolic networks in accordance with stress, and so forth, in order to overcome abiotic stress factors. Many structural genes and networks of pathway were identified and reported in plant systems for abiotic stress tolerance. One such crucial metabolic pathway that is involved in normal physiological function and also gets modulated during stress to impart tolerance is polyamine metabolic pathway. Besides the role of structural genes, it is also important to know the mechanism by which these structural genes are regulated during stress. Present review highlights polyamine biosynthesis, catabolism, and its role in abiotic stress tolerance with special reference to plant systems. Additionally, a system based approach is discussed as a potential strategy to dissect the existing variation in crop species in unraveling the interacting regulatory components/genetic determinants related to PAs mediated abiotic stress tolerance.

  8. A Polyamine Metabolon Involving Aminopropyl Transferase Complexes in Arabidopsis

    Science.gov (United States)

    Panicot, Mireia; Minguet, Eugenio G.; Ferrando, Alejandro; Alcázar, Rubén; Blázquez, Miguel A.; Carbonell, Juan; Altabella, Teresa; Koncz, Csaba; Tiburcio, Antonio F.

    2002-01-01

    The conversion of putrescine to spermidine in the biosynthetic pathway of plant polyamines is catalyzed by two closely related spermidine synthases, SPDS1 and SPDS2, in Arabidopsis. In the yeast two-hybrid system, SPDS2 was found to interact with SPDS1 and a novel protein, SPMS (spermine synthase), which is homologous with SPDS2 and SPDS1. SPMS interacts with both SPDS1 and SPDS2 in yeast and in vitro. Unlike SPDS1 and SPDS2, SPMS failed to suppress the speΔ3 deficiency of spermidine synthase in yeast. However, SPMS was able to complement the speΔ4 spermine deficiency in yeast, indicating that SPMS is a novel spermine synthase. The SPDS and SPMS proteins showed no homodimerization but formed heterodimers in vitro. Pairwise coexpression of hemagglutinin- and c-Myc epitope–labeled proteins in Arabidopsis cells confirmed the existence of coimmunoprecipitating SPDS1-SPDS2 and SDPS2-SPMS heterodimers in vivo. The epitope-labeled SPDS and SPMS proteins copurified with protein complexes ranging in size from 650 to 750 kD. Our data demonstrate the existence of a metabolon involving at least the last two steps of polyamine biosynthesis in Arabidopsis. PMID:12368503

  9. Raman study of the effects of polyamines on DNA:spermine and histamine

    Science.gov (United States)

    Ruiz-Chica, J.; Medina, M. A.; Sánchez-Jiménez, F.; Ramírez, F. J.

    1999-05-01

    Fourier transform Raman spectroscopy was used to investigate the interaction of spermine and histamine with calf-thymus DNA. Polyamine-DNA solutions at different polyamine concentrations ranging from 5 mM to 75 mM were prepared. For spermine, solutions no higher than 15 mM were prepared because this molecule induces condensation and aggregation on DNA at upper concentrations. Possible sites of bindings for polyamine-DNA complexes were discussed on the basis of the spectral changes observed with respect to the Raman spectra of DNA. The results seem to indicate that one spermine molecule induces on DNA a similar effect to two or more histamine molecules.

  10. Surface characterization and stability of an epoxy resin surface modified with polyamines grafted on polydopamine

    Energy Technology Data Exchange (ETDEWEB)

    Schaubroeck, David, E-mail: David.Schaubroeck@elis.ugent.be [Center for Microsystems Technology (CMST), imec and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium); Vercammen, Yannick; Van Vaeck, Luc [Biomolecular and Analytical Mass Spectrometry, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk (Belgium); Vanderleyden, Els; Dubruel, Peter [Polymer Chemistry and Biomaterials Research Group, Ghent University, Krijgslaan 281 S4 bis, B-9000 Ghent (Belgium); Vanfleteren, Jan [Center for Microsystems Technology (CMST), imec and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium)

    2014-06-01

    This paper reports on polydopamine and polyamine surface modifications of an etched epoxy cresol novolac (ECN) resin using the ‘grafting to’ method. Three different polyamines are used for the grafting reactions: branched polyethyleneimine (B-PEI), linear polyethyleneimine (L-PEI) and diethylenetriamine (DETA). These modifications are compared to control materials prepared via direct deposition of polyamines. The stability of the modifications toward a concentrated hydrochloric acid (HCl) environment is evaluated. The modified surfaces are characterized with scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectroscopy (TOF-S-SIMS).

  11. Surface modification of an epoxy resin with polyamines and polydopamine: Adhesion toward electroless deposited copper

    Science.gov (United States)

    Schaubroeck, David; Mader, Lothar; Dubruel, Peter; Vanfleteren, Jan

    2015-10-01

    In this paper the influence of the epoxy roughness, surface modifications and ELD (electroless copper deposition) temperatures on the adhesive strength of the copper is studied. Good adhesion at low roughness values is targeted due to their applicability in high density electronic circuits. Roughened epoxy surfaces are modified with adsorbed polyamines, polydopamine and polyamines grafted to polydopamine. Next the, adhesive strength of ELD copper is determined with peel strength measurements and the interphases are examined with SEM (scanning electron microscopy). Polydopamine and polyamines grafted to polydopamine can lead to increased adhesive strength at lower roughness values compared to the non-modified samples at specific plating temperatures.

  12. Polyamines inhibit biosynthesis of ethylene in higher plant tissue and fruit protoplasts.

    Science.gov (United States)

    Apelbaum, A; Burgoon, A C; Anderson, J D; Lieberman, M

    1981-08-01

    Ethylene production in apple fruit and protoplasts and in leaf tissue was inhibited by spermidine or spermine. These polyamines, as well as putrescine, inhibited auxin-induced ethylene production and the conversion of methionine and 1-aminocyclopropane-1-carboxylic acid to ethylene. Polyamines were more effective as inhibitors of ethylene synthesis at the early, rather than at the late, stages of fruit ripening. Ca(2+) in the incubation medium reduced the inhibitory effect caused by the amines. A possible mode of action by which polyamines inhibit ethylene production is discussed.

  13. Separation of polyamines, conjugated to DNA, by reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Mateos, J L; Reyes, A; Vicente, C; Legaz, M E

    2000-02-18

    Genomic DNA was isolated from the lichen Evernia prunastri in order to analyze by high-performance liquid chromatography the occurrence of polyamines conjugated to the macromolecule. The acid-insoluble (PH) fraction of this DNA contained mainly conjugated spermidine, although small amounts of free putrescine and spermidine were also present. The PH fraction of DNA also contained conjugated evernic acid, the main phenol produced by this lichen species. Conjugation of polyamines to calf thymus DNA was carried out under in vitro conditions. Conjugation was to spermidine and mainly to spermine and produced DNA compactation. Evernic acid enhanced the action of polyamines in order to produce DNA aggregation.

  14. The Human Carnitine Transporter SLC22A16 Mediates High Affinity Uptake of the Anticancer Polyamine Analogue Bleomycin-A5*

    Science.gov (United States)

    Aouida, Mustapha; Poulin, Richard; Ramotar, Dindial

    2010-01-01

    Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae l-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human l-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, l-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients. PMID:20037140

  15. The human carnitine transporter SLC22A16 mediates high affinity uptake of the anticancer polyamine analogue bleomycin-A5.

    Science.gov (United States)

    Aouida, Mustapha; Poulin, Richard; Ramotar, Dindial

    2010-02-26

    Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae L-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human L-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, L-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients.

  16. Groundwater depletion embedded in international food trade

    Science.gov (United States)

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J.

    2017-03-01

    Recent hydrological modelling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world’s food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world’s population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  17. The New MCNP6 Depletion Capability

    Energy Technology Data Exchange (ETDEWEB)

    Fensin, Michael Lorne [Los Alamos National Laboratory; James, Michael R. [Los Alamos National Laboratory; Hendricks, John S. [Los Alamos National Laboratory; Goorley, John T. [Los Alamos National Laboratory

    2012-06-19

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  18. Polyamine levels as related to growth, differentiation and senescence in protoplast-derived cultures of Vigna aconitifolia and Avena sativa

    Science.gov (United States)

    Kaur Sawhney, R.; Shekhawat, N. S.; Galston, A. W.

    1985-01-01

    We have previously reported that aseptically cultured mesophyll protoplasts of Vigna divide rapidly and regenerate into complete plants, while mesophyll protoplasts of Avena divide only sporadically and senesce rapidly after isolation. We measured polyamine titers in such cultures of Vigna and Avena, to study possible correlations between polyamines and cellular behavior. We also deliberately altered polyamine titer by the use of selective inhibitors of polyamine biosynthesis, noting the effects on internal polyamine titer, cell division activity and regenerative events. In Vigna cultures, levels of free and bound putrescine and spermidine increased dramatically as cell division and differentiation progressed. The increase in bound polyamines was largest in embryoid-forming callus tissue while free polyamine titer was highest in root-forming callus. In Avena cultures, the levels of total polyamines decreased as the protoplast senesced. The presence of the inhibitors alpha-difluoromethyl-arginine (specific inhibitor of arginine decarboxylase), alpha-difluoromethylornithine (specific inhibitor of ornithine decarboxylase) and dicyclohexylamine (inhibitor of spermidine synthase) reduced cell division and organogenesis in Vigna cultures. Addition of low concentration of polyamines to such cultures containing inhibitors or removal of inhibitors from the culture medium restored the progress of growth and differentiation with concomitant increase in polyamine levels.

  19. Abscisic acid signals reorientation of polyamine metabolism to orchestrate stress responses via the polyamine exodus pathway in grapevine.

    Science.gov (United States)

    Toumi, Imene; Moschou, Panagiotis N; Paschalidis, Konstantinos A; Bouamama, Badra; Ben Salem-Fnayou, Asma; Ghorbel, Abdel Wahed; Mliki, Ahmed; Roubelakis-Angelakis, Kalliopi A

    2010-05-01

    Polyamines (PAs) have been suggested to be implicated in plant responses to abiotic and biotic stress. Grapevine is a model perennial plant species whose cultivars respond differently to osmotic stress. In this study, we used two cultivars, one sensitive (S) and one tolerant (T) to drought. In adult vines subjected to drought under greenhouse conditions, total PAs were significantly lower in the control T- and higher in the control S-genotype and significantly increased or decreased, respectively, post-treatment. Soluble Put and Spd exhibited the greatest increase on d 8 post-treatment in the T- but not in the S-genotype, which accumulated soluble Spm. Abscisic acid (ABA) was differentially accumulated in T- and S-genotypes under drought conditions, and activated the PA biosynthetic pathway, which in turn was correlated with the differential increases in PA titers. In parallel, polyamine oxidases (PAOs) increased primarily in the S-genotype. ABA at least partially induced PA accumulation and exodus into the apoplast, where they were oxidized by the apoplastic amine oxidases (AOs), producing H2O2, which signaled secondary stress responses. The results here show that the ABA signaling pathway integrates PAs and AOs to regulate the generation of H2O2, which signals further stress responses or the PCD syndrome.

  20. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes.

    Science.gov (United States)

    Huang, Yi; Greene, Eriko; Murray Stewart, Tracy; Goodwin, Andrew C; Baylin, Stephen B; Woster, Patrick M; Casero, Robert A

    2007-05-08

    Epigenetic chromatin modification is a major regulator of eukaryotic gene expression, and aberrant epigenetic silencing of gene expression contributes to tumorigenesis. Histone modifications include acetylation, phosphorylation, and methylation, resulting in a combination of histone marks known collectively as the histone code. The chromatin marks at a given promoter determine, in part, whether specific promoters are in an open/active conformation or closed/repressed conformation. Dimethyl-lysine 4 histone H3 (H3K4me2) is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by the lysine-specific demethylase 1 (LSD1), a homologue of polyamine oxidases, may broadly repress gene expression. We now report that novel biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1. These analogues inhibit LSD1 in human colon carcinoma cells and affect a reexpression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins (SFRPs) and the GATA family of transcription factors. Furthermore, we demonstrate by chromatin immunoprecipitation analysis that the reexpression is concurrent with increased H3K4me2 and acetyl-H3K9 marks, decreased H3K9me1 and H3K9me2 repressive marks. We thus define important new agents for reversing aberrant repression of gene transcription.

  1. Histone deacetylase 10 structure and molecular function as a polyamine deacetylase

    Science.gov (United States)

    Hai, Yang; Shinsky, Stephen A.; Porter, Nicholas J.; Christianson, David W.

    2017-05-01

    Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish). The 2.85 Å-resolution crystal structure of zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Both HDAC10 and spermidine are known to promote cellular survival through autophagy. Accordingly, this work sets a foundation for studying the chemical biology of autophagy through the structure-based design of inhibitors that may also serve as new leads for cancer chemotherapy.

  2. Intracellular polyamine pools, oligopeptide-binding protein A expression, and resistance to aminoglycosides in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Maria BR Acosta

    2005-11-01

    Full Text Available The role of intracellular free polyamine (putrescine and spermidine pools in multiple resistance to aminoglycoside antibiotics was investigated among in vitro selected kanamycin-resistant Escherichia coli J53 mutants expressing diminished oligopeptide-binding protein (OppA levels and/or defective ornithine decarboxylase (ODC activity. The results suggest that diminished OppA content, but not defective ODC activity expression, increased the relative concentration of free spermidine as compared to the wild type strain. Moreover, by adding exogenous polyamines or polyamine synthesis inhibitors to cultures with different mutant strains, a direct relationship between the intracellular OppA levels and resistance to kanamycin was revealed. Collectively these results further suggest a complex relation among OppA expression, aminoglycoside resistance and polyamine metabolism.

  3. Polyamine metabolism in prostate cancer : studies on localization, cell growth and apoptosis

    NARCIS (Netherlands)

    Schipper, Raymond Godfried

    2000-01-01

    The involvement of polyamines in cellular growth and differentiation has prompted many studies of their possible role in cellular neoplasia, including prostatic carcinoma and benign hyperplasia, which represent increasingly important pathologies in men. The precise role of the

  4. Structure of Prokaryotic Polyamine Deacetylase Reveals Evolutionary Functional Relationships with Eukaryotic Histone Deacetylases

    Energy Technology Data Exchange (ETDEWEB)

    P Lombardi; H Angell; D Whittington; E Flynn; K Rajashankar; D Christianson

    2011-12-31

    Polyamines are a ubiquitous class of polycationic small molecules that can influence gene expression by binding to nucleic acids. Reversible polyamine acetylation regulates nucleic acid binding and is required for normal cell cycle progression and proliferation. Here, we report the structures of Mycoplana ramosa acetylpolyamine amidohydrolase (APAH) complexed with a transition state analogue and a hydroxamate inhibitor and an inactive mutant complexed with two acetylpolyamine substrates. The structure of APAH is the first of a histone deacetylase-like oligomer and reveals that an 18-residue insert in the L2 loop promotes dimerization and the formation of an 18 {angstrom} long 'L'-shaped active site tunnel at the dimer interface, accessible only to narrow and flexible substrates. The importance of dimerization for polyamine deacetylase function leads to the suggestion that a comparable dimeric or double-domain histone deacetylase could catalyze polyamine deacetylation reactions in eukaryotes.

  5. Free polyamine content during algal bloom succession in the East China Sea in spring 2010

    Science.gov (United States)

    Liu, Yan; Zhao, Weihong; Li, Caiyan; Miao, Hui

    2017-01-01

    We measured the concentrations and distribution of major polyamines (spermine, putrescine and spermidine) in seawater during successive spring algal blooms in an area of frequent harmful blooms in the East China Sea. Spermine, putrescine, and spermidine concentrations were analyzed by high performance liquid chromatography and ranged from 1-64, 7-81, and 0-19 nmol/L. Spermine was present at the highest concentrations, followed by putrescine and spermidine. In late April, when a diatom bloom dominated by Skeletonema costatum dispersed, polyamine concentrations increased, presumably as a result of diatom decomposition. In early May, when a dinoflagellate bloom dominated by Prorocentrum donghaiense occurred, the polyamine concentration decreased from the level seen in late April. The abundant polyamines that decomposed and were released during the diatom bloom in late April may have promoted the growth of P. donghaiense, resulting in its dominance.

  6. Ozone Depletion by Hydrofluorocarbons

    Science.gov (United States)

    Hurwitz, M.; Fleming, E. L.; Newman, P. A.; Li, F.; Mlawer, E. J.; Cady-Pereira, K. E.; Bailey, R.

    2015-12-01

    Hydrofluorocarbons (HFCs) are second-generation replacements for the chlorofluorocarbons (CFCs), halons and other substances that caused the 'ozone hole'. Atmospheric concentrations of HFCs are projected to increase dramatically in the coming decades. Coupled chemistry-climate simulations forced by these projections show that HFCs will impact the global atmosphere in 2050. As strong radiative forcers, HFCs modulate atmospheric temperature, thereby changing ozone-destroying catalytic cycles and enhancing the stratospheric circulation. These changes lead to a weak depletion of stratospheric ozone. Sensitivity simulations with the NASA Goddard Space Flight Center (GSFC) 2D model show that HFC-125 is the most important contributor to atmospheric change in 2050, as compared with HFC-23, HFC-32, HFC-134a and HFC-143a. Incorporating the interactions between chemistry, radiation and dynamics, for a likely 2050 climate, ozone depletion potentials (ODPs) for HFCs range from 4.3x10-4 to 3.5x10-2; previously HFCs were assumed to have negligible ODPs since these species lack chlorine or bromine atoms. The ozone impacts of HFCs are further investigated with the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM). The GEOSCCM is a three-dimensional, fully coupled ocean-atmosphere model with interactive stratospheric chemistry. Sensitivity simulations in which CO2, CFC-11 and HCFC-22 are enhanced individually are used as proxies for the atmospheric response to the HFC concentrations expected by the mid-21st century. Sensitivity simulations provide quantitative estimates of the impacts of these greenhouse gases on global total ozone, and can be used to assess their effects on the recovery of Antarctic ozone.

  7. Functional analysis of OsPUT1, a rice polyamine uptake transporter.

    Science.gov (United States)

    Mulangi, Vaishali; Phuntumart, Vipaporn; Aouida, Mustapha; Ramotar, Dindial; Morris, Paul

    2012-01-01

    Polyamines are nitrogenous compounds found in all eukaryotic and prokaryotic cells and absolutely essential for cell viability. In plants, they regulate several growth and developmental processes and the levels of polyamines are also correlated with the plant responses to various biotic and abiotic stresses. In plant cells, polyamines are synthesized in plastids and cytosol. This biosynthetic compartmentation indicates that the specific transporters are essential to transport polyamines between the cellular compartments. In the present study, a phylogenetic analysis was used to identify candidate polyamine transporters in rice. A full-length cDNA rice clone AK068055 was heterologously expressed in the Saccharomyces cerevisiae spermidine uptake mutant, agp2∆. Radiological uptake and competitive inhibition studies with putrescine indicated that rice gene encodes a protein that functioned as a spermidine-preferential transporter. In competition experiments with several amino acids at 25-fold higher levels than spermidine, only methionine, asparagine, and glutamine were effective in reducing uptake of spermidine to 60% of control rates. Based on those observations, this rice gene was named polyamine uptake transporter 1 (OsPUT1). Tissue-specific expression of OsPUT1 by semiquantitative RT-PCR showed that the gene was expressed in all tissues except seeds and roots. Transient expression assays in onion epidermal cells and rice protoplasts failed to localize to a cellular compartment. The characterization of the first plant polyamine transporter sets the stage for a systems approach that can be used to build a model to fully define how the biosynthesis, degradation, and transport of polyamines in plants mediate developmental and biotic responses.

  8. Multiscale modelling approach combining a kinetic model of glutathione metabolism with PBPK models of paracetamol and the potential glutathione-depletion biomarkers ophthalmic acid and 5-oxoproline in humans and rats

    NARCIS (Netherlands)

    Geenen, S.; Yates, J.W.T.; Kenna, J.G.; Bois, F.Y.; Wilson, I.D.; Westerhoff, H.V.

    2013-01-01

    A key role of the antioxidant glutathione is detoxification of chemically reactive electrophilic drug metabolites within the liver. Therefore glutathione depletion can have severe toxic consequences. Ophthalmic acid and 5-oxoproline are metabolites involved in glutathione metabolism, which can be me

  9. Investigation of intranodal depletion effects

    Energy Technology Data Exchange (ETDEWEB)

    Forslund, P. E-mail: petri.forslund@se.abb.com; Mueller, E.; Lindahl, S

    2001-02-01

    The modeling of depletion induced intranodal effects on important neutron physical parameters in nodal diffusion theory is addressed. Consideration is given to two situations where these aspects are of particular interest, namely, in mixed oxide cores where strong interaction between uranium and plutonium mixed oxide assemblies occur, and in boiling water reactor cores where significant control rod history effects are encountered. A model based on a low order polynomial representation of intranodal cross-section spatial behaviour is considered. Two approaches for determining the constraints for the polynomial fitting procedure are applied. The first one is a conventional method employing intranodal exposure values, whereas the second model combines intranodal exposure and isotopic inventory information. Numerical studies are performed in order to evaluate the relative merits of the different models. It is demonstrated that pin power predictions are significantly influenced by intranodal effects. It is also found that the combined use of intranodal isotopic inventory and exposure distributions for estimating intranodal cross-section behaviour significantly improves the accuracy in pin powers over the more traditional approach of utilizing exposure distributions only.

  10. Nanoplugging Performance of Hyperbranched Polyamine as Nanoplugging Agent in Oil-Based Drilling Fluid

    Directory of Open Access Journals (Sweden)

    Gang Xie

    2015-01-01

    Full Text Available A hyperbranched polyamine was synthesized by self-condensing vinyl polymerization with divinyl sulfone, N-phenyl-p-phenylenediamine, by A2 + BB2' approach. The hyperbranched polyamine was characterized by FT-IR, TGA, and phase analysis light scanning. Average grain diameter of hyperbranched polyamine was 36.7 nm. Hyperbranched polyamine has good thermal stability. Hyperbranched polyamine (HBPA was employed successfully as nanoplugging agent in oil-based drilling fluid system, which could plug nanopore formation in shale formation. HBPA has a little effect on rheological properties of oil-based drilling fluid and the FLAPI and FLHTHP decreased dramatically with an increase of hyperbranched polyamine. Emulsion-breaking voltage has a slight increase, which is beneficial to maintain stability of oil-based drilling fluid. When the HBPA concentration is greater than 1 wt%, plugging rate of oil-based drilling fluid for artificial core is close to 100% and the permeability recovery value can reach 99.7% after adding 1 wt% HBPA, which prove that HBPA has an excellent plugging performance.

  11. Targeting the polyamine-hypusine circuit for the prevention and treatment of cancer.

    Science.gov (United States)

    Nakanishi, Shima; Cleveland, John L

    2016-10-01

    The unique amino acid hypusine is present in only two proteins in eukaryotic cells, eukaryotic translation initiation factor 5A-1 (eIF5A1), and eIF5A2, where it is covalently linked to the lysine-50 residue of these proteins via a post-translational modification coined hypusination. This unique modification is directed by two highly conserved and essential enzymes, deoxyhypusine synthase (DHPS), and deoxyhypusine hydroxylase (DOHH), which selectively use the polyamine spermidine as a substrate to generate hypusinated eIF5A. Notably, elevated levels of polyamines are a hallmark of most tumor types, and increased levels of polyamines can also be detected in the urine and blood of cancer patients. Further, in-clinic agents that block the function of key biosynthetic enzymes in the polyamine pathway markedly impair tumor progression and maintenance of the malignant state. Thus, the polyamine pathway is attractive as a prognostic, prevention and therapeutic target. As we review, recent advances in our understanding of the specific functions of hypusinated eIF5A and its role in tumorigenesis suggest that the polyamine-hypusine circuit is a high priority target for cancer therapeutics.

  12. OBSERVATION ON CHANGES OF ERYTHROCYTE POLYAMINE LEVELS IN LEUKEMIA PATIENTS

    Institute of Scientific and Technical Information of China (English)

    缪金明; 欧阳仁荣; 潘瑞彭

    1993-01-01

    In an observation on erythrocyte polyamine levels in leukemia patients andhealthy individuals, the following results were obtained. (1) Putrescine (Pu) inerythrocytes was nearly undetectable but in two AMoL patients; (2) Spermidine (Spd)level in ALL was higher than the control value (P<0.05); while in AML (M1, M2)and APL the Spd level was in the range of control (P>0.1): and that in AMoL andAMMoL was considerably lower as compared to control (P<0.001); (3) Spermine(Spm) level in all types of leukemia was increased (P<0.001); (4) Spd/Spm ratiowas significantly decreased as compared to control value (1.525), showing 0.938 inALL (P<0.025); 0.779 in AML (M1, M2)(P<0.01), 0.319 in APL (P<0.001) and0.296 in AMoL and AMMoL (P<0.001), and the differences between the Spd/Spm ra-tio in AMoL and AMMoL and in ALL were noted (P<0.05); (5) Spd and Spm le-vels in erythrocytes in the patients after effective chemotherapy declined significantly(P<0.05) but were still higher than control value (P<0.025). These results suggestthat the determination of erythrocyte polyamines in leukemia patients may be helpful indiagnosis, differential diagnosis and prognosis.

  13. Depleted zinc: Properties, application, production.

    Science.gov (United States)

    Borisevich, V D; Pavlov, A V; Okhotina, I A

    2009-01-01

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  14. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha

    2013-06-03

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  15. Surface modification of an epoxy resin with polyamines and polydopamine: The effect on the initial electroless copper deposition

    Science.gov (United States)

    Schaubroeck, David; Mader, Lothar; De Geyter, Nathalie; Morent, Rino; Dubruel, Peter; Vanfleteren, Jan

    2014-06-01

    This paper describes the influence of polydopamine and polyamine surface modifications of an etched epoxy cresol novolak (ECN) resin on the initial electroless copper deposition. Three different strategies to introduce polyamines on a surface in aqueous environment are applied: via polyethyleneimine adsorption (PEI), via polydopamine and via polyamines grafted to polydopamine. Next, the influence of these surface modifications on the catalytic palladium activation is investigated through X-ray photoelectron spectroscopy (XPS) analysis. Finally, the initial electroless copper deposition on modified epoxy surfaces is evaluated using SEM and Energy Dispersive Spectroscopy (EDS). Grafted polyamines on polydopamine surface modifications result in a large increase of the initial deposited copper.

  16. Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.

    Directory of Open Access Journals (Sweden)

    Mustapha Aouida

    Full Text Available Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2Δ mutant. Studies of Agp2 localization indicate that in the double mutant dur3Δ sam3Δ, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport.

  17. Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.

    Science.gov (United States)

    Aouida, Mustapha; Rubio-Texeira, Marta; Rubio Texeira, Marta; Thevelein, Johan M; Poulin, Richard; Ramotar, Dindial

    2013-01-01

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2Δ mutant. Studies of Agp2 localization indicate that in the double mutant dur3Δ sam3Δ, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport.

  18. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    OpenAIRE

    Mustapha Aouida; Marta Rubio-Texeira; Thevelein, Johan M.; Richard Poulin; Dindial Ramotar

    2013-01-01

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant e...

  19. Effective Depletion Potential of Colloidal Spheres

    Institute of Scientific and Technical Information of China (English)

    LI Wei-Hua; MA Hong-Ru

    2004-01-01

    @@ A new semianalytical method, which is a combination of the density functional theory with Rosenfeld density functional and the Ornstein-Zernike equation, is proposed for the calculation of the effective depletion potentials between a pair of big spheres immersed in a small hard sphere fluid. The calculated results are almost identical to the integral equation method with the Percus-Yevick approximation, and are also in agreement well with the Monte Carlo simulation results.

  20. Ego depletion impairs implicit learning.

    Science.gov (United States)

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  1. Depletable resources and the economy.

    NARCIS (Netherlands)

    Heijman, W.J.M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, ti

  2. Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.

    Science.gov (United States)

    Zhang, Pan; Yang, Hui; Wang, Guojun; Tong, Weijun; Gao, Changyou

    2016-06-01

    The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization.

  3. Inhibition of polyamine biosynthesis and growth in plant pathogenic fungi in vitro.

    Science.gov (United States)

    Rajam, B; Rajam, M V

    1996-02-01

    Polyamine (PA) biosynthesis inhibitors, difluoromethylornithine (DFMO), difluoromethylarginine (DFMA), methylglyoxal bis-(guanylhydrazone) (MGBG) and bis-(cyclohexylammonium) sulphate (BCHA) have been tested for their effects on colony diameters at different intervals after inoculation of four plant pathogenic fungi (Helminthosporium oryzae, Curvularia lunata, Pythium aphanidermatum and Colletotrichum capsici). All these inhibitors, except DFMA had strongly retarded the growth of four fungi in a dose- and species-dependent fashion, and H. oryzae and C. lunata were found to be most sensitive to the effects of PA inhibitors. P. aphanidermatum and C. capsici were relatively insensitive and required rather high concentrations of inhibitors to get greater inhibition of mycelial growth, except DFMA which had stimulatory effect on the growth of these two fungi. However DFMA had greatly suppressed the growth of H. oryzae and C. lunata. The effect was generally more pronounced with MGBG than with DFMO and BCHA, and 1 mM Put completely prevented the inhibitory effects of 1 and 5 mM DFMO. Analysis of free and conjugated PAs in two sensitive fungi (H. oryzae and C. lunata) revealed that Put was present in highest concentrations followed by Spd and Spm and their levels were greatly reduced by DFMO application, and such inhibitions were totally reversed by exogenously supplied Put; in fact, PA titers were considerably increased by 1 mM Put alone and in combination with 1 mM DFMO. These results suggest that PA inhibitors, particularly DFMO and MGBG may be useful as target-specific fungicides in plants.

  4. Interaction of brassinosteroids and polyamines enhances copper stress tolerance in raphanus sativus.

    Science.gov (United States)

    Choudhary, Sikander Pal; Oral, H Volkan; Bhardwaj, Renu; Yu, Jing-Quan; Tran, Lam-Son Phan

    2012-09-01

    Brassinosteroids (BRs) and polyamines (PAs) regulate various responses to abiotic stress, but their involvement in the regulation of copper (Cu) homeostasis in plants exposed to toxic levels of Cu is poorly understood. This study provides an analysis of the effects of exogenously applied BRs and PAs on radish (Raphanus sativus) plants exposed to toxic concentrations of Cu. The interaction of 24-epibrassinolide (EBR, an active BR) and spermidine (Spd, an active PA) on gene expression and the physiology of radish plants resulted in enhanced tolerance to Cu stress. Results indicated that the combined application of EBR and Spd modulated the expression of genes encoding PA enzymes and genes that impact the metabolism of indole-3-acetic acid (IAA) and abscisic acid (ABA) resulting in enhanced Cu stress tolerance. Altered expression of genes implicated in Cu homeostasis appeared to be the main effect of EBR and Spd leading to Cu stress alleviation in radish. Ion leakage, in vivo imaging of H(2)O(2), comet assay, and improved tolerance of Cu-sensitive yeast strains provided further evidence for the ability of EBR and Spd to improve Cu tolerance significantly. The study indicates that co-application of EBR and Spd is an effective approach for Cu detoxification and the maintenance of Cu homeostasis in plants. Therefore, the use of these compounds in agricultural production systems should be explored.

  5. Senescence and programmed cell death in plants: polyamine action mediated by transglutaminase

    Directory of Open Access Journals (Sweden)

    Stefano eDel Duca

    2014-04-01

    Full Text Available Research on polyamines in plants laps a long way of about 50 years and many roles have been discovered for these aliphatic cations. Polyamines regulate cell division, differentiation, organogenesis, reproduction, dormancy-break and senescence, homeostatic adjustments in response to external stimuli and stresses. Nevertheless, the molecular mechanisms of their multiple activities are still matter of research. Polyamines are present in free and bound forms and interact with several important cell molecules; some of these interactions may occur by covalent linkages catalyzed by transglutaminase, giving rise to ‘cationisation’ or cross-links among specific proteins. Senescence and PCD can be delayed by polyamines; in order to re-interpret some of these effects and to obtain new insights into their molecular mechanisms, their conjugation has been revised here. The transglutaminase-mediated interactions between proteins and polyamines are the main target of this review. After an introduction on the characteristics of this enzyme, on its catalysis and role in PCD in animals, the plant senescence and PCD models in which TGase has been studied, are presented: the corolla of naturally senescing or excised flowers, the leaves senescing, either excised or not, the pollen during self-incompatible pollination, the hypersensitive response and the tuber storage parenchyma during dormancy release. In all the models examined, transglutaminase appears to be involved by a similar molecular mechanism as described during apoptosis in animal cells, even though several substrates are different. Its effect is probably related to the type of PCD, but mostly to the substrate to be modified in order to achieve the specific PCD program. As a cross-linker of polyamines and proteins, transglutaminase is an important factor involved in multiple, sometimes controversial, roles of polyamines during senescence and PCD.

  6. Wounding induces changes in tuber polyamine content, polyamine metabolic gene expression, and enzyme activity during closing layer formation and initiation of wound periderm formation

    Science.gov (United States)

    Tuber wound-healing processes are complex, and the associated regulation and modulation of these processes are poorly understood. Polyamines (PA) have been shown to be involved in modulating a variety of responses to biotic and abiotic plant stresses and have been suggested to be involved in tuber ...

  7. Analysis and Application of Whey Protein Depleted Skim Milk Systems

    DEFF Research Database (Denmark)

    Sørensen, Hanne

    homogenisation (UHPH). The microfiltration will result in a milk fraction more or less depleted from whey protein, and could probably in combination with UHPH treatment contribute to milk fractions and cheeses with novel micro and macrostructures. These novel fractions could be used as new ingredients to improve......-destructive methods for this purpose. A significant changed structure was observed in skim milk depleted or partly depleted for whey protein, acidified and UHPH treated. Some of the properties of the UHPH treated skim milk depleted from whey protein observed in this study support the idea, that UHPH treatment has...... this. LF-NMR relaxation were utilised to obtain information about the water mobility (relaxation time), in diluted skim milk systems depleted from whey protein. Obtained results indicate that measuring relaxation times with LF-NMR could be difficult to utilize, since no clear relationship between...

  8. Testing fully depleted CCD

    Science.gov (United States)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  9. How Depleted is the MORB mantle?

    Science.gov (United States)

    Hofmann, A. W.; Hart, S. R.

    2015-12-01

    Knowledge of the degree of mantle depletion of highly incompatible elements is critically important for assessing Earth's internal heat production and Urey number. Current views of the degree of MORB source depletion are dominated by Salters and Stracke (2004), and Workman and Hart (2005). The first is based on an assessment of average MORB compositions, whereas the second considers trace element data of oceanic peridotites. Both require an independent determination of one absolute concentration, Lu (Salters & Stracke), or Nd (Workman & Hart). Both use parent-daughter ratios Lu/Hf, Sm/Nd, and Rb/Sr calculated from MORB isotopes combined with continental-crust extraction models, as well as "canonical" trace element ratios, to boot-strap the full range of trace element abundances. We show that the single most important factor in determining the ultimate degree of incompatible element depletion in the MORB source lies in the assumptions about the timing of continent extraction, exemplified by continuous extraction versus simple two-stage models. Continued crust extraction generates additional, recent mantle depletion, without affecting the isotopic composition of the residual mantle significantly. Previous emphasis on chemical compositions of MORB and/or peridotites has tended to obscure this. We will explore the effect of different continent extraction models on the degree of U, Th, and K depletion in the MORB source. Given the uncertainties of the two most popular models, the uncertainties of U and Th in DMM are at least ±50%, and this impacts the constraints on the terrestrial Urey ratio. Salters, F.J.M. and Stracke, A., 2004, Geochem. Geophys. Geosyst. 5, Q05004. Workman, R.K. and Hart, S.R., 2005, EPSL 231, 53-72.

  10. The effect of polyamine biosynthesis inhibition on growth and differentiation of the phytopathogenic fungus Sclerotinia sclerotiorum.

    Science.gov (United States)

    Pieckenstain, F L; Gárriz, A; Chornomaz, E M; Sánchez, D H; Ruiz, O A

    2001-12-01

    We studied the effects of several polyamine biosynthesis inhibitors on growth, differentiation, free polyamine levels and in vivo and in vitro activity of polyamine biosynthesis enzymes in Sclerotinia sclerotiorum. Alpha-Difluoromethylornithine (DFMO) and alpha-difluoromethylarginine (DFMA) were potent inhibitors of mycelial growth. The effect of DFMO was due to inhibition of ornithine decarboxylase (ODC). No evidence for the existence of an arginine decarboxylase (ADC) pathway was found. The effect of DFMA was partly due to inhibition of ODC, presumably after its conversion into DFMO by mycelial arginase, as suggested by the high activity of this enzyme detected both in intact mycelium and mycelial extracts. In addition, toxic effects of DFMA on cellular processes other than polyamine metabolism might have occurred. Cyclohexylamine (CHA) slightly inhibited mycelial growth and caused an important decrease of free spermidine associated with a drastic increase of free putrescine concentration. Methylglyoxal bis-[guanyl hydrazone] (MGBG) had no effect on mycelial growth. Excepting MGBG, all the inhibitors strongly decreased sclerotial formation. Results demonstrate that sclerotial development is much more sensitive to polyamine biosynthesis inhibition than mycelial growth. Our results suggest that mycelial growth can be supported either by spermidine or putrescine, while spermidine (or the putrescine/spermidine ratio) is important for sclerotial formation to occur. Ascospore germination was completely insensitive to the inhibitors.

  11. Genotype differences in the metabolism of proline and polyamines under moderate drought in tomato plants.

    Science.gov (United States)

    Montesinos-Pereira, D; Barrameda-Medina, Y; Romero, L; Ruiz, J M; Sánchez-Rodríguez, E

    2014-11-01

    Water stress is one of the most important factors limiting the growth and productivity of crops. The implication of compatible osmolytes such as proline and polyamines in osmotic adjustment has been widely described in numerous plants species under stress conditions. In the present study, we investigated the response of five cherry tomato cultivars (Solanum lycopersicum L.) subjected to moderate water stress in order to shed light on the involvement of proline and polyamine metabolism in the mechanisms of tolerance to moderate water stress. Our results indicate that the most water stress-resistant cultivar (Zarina) had increased degradation of proline associated with increased polyamine synthesis, with a higher concentration of spermidine and spermine under stress conditions. In contrast, Josefina, the cultivar most sensitive to water stress, showed a proline accumulation associated with increased synthesis after being subjected to stress. In turn, in this cultivar, no rise in polyamine synthesis was detected. Therefore, all the data appear to indicate that polyamine metabolism is more involved in the tolerance response to moderate water stress.

  12. Free and conjugated polyamines and phenols in raw and alkaline-clarified sugarcane juices.

    Science.gov (United States)

    de Armas, R; Martinez, M; Vicente, C; Legaz, M E

    1999-08-01

    Sugarcane juice contains a lot of sucrose associated with several monosaccharides, defined as low molecular mass carbohydrates (LMMC), as well as some polysaccharides and glycoproteins, which are defined as mid and high molecular mass carbohydrates (MMMC and HMMC, respectively). These three categories of carbohydrates can be separated by size-exclusion chromatography through Sephadex G-10 and Sephadex G-50 columns, but elution profiles change drastically after juice clarification performed by adjusting the pH value of the juice to 8.0. In addition, polyamines and some phenolics are currently associated with carbohydrate preparations, and the distribution pattern of these conjugates also changes after clarification. Polyamine levels generally decrease after juice clarification. Cadaverine is completely removed from the different carbohydrate preparations, whereas spermidine is the main polyamine occurring in association with sugarcane carbohydrates, as free or acid-soluble form in LMMC preparation or as acid-soluble and -insoluble forms in both MMMC and HMMC preparations. Polyamines, presumably spermidine, conjugate to p-hydroxybenzoic acid in LMMC, mostly to caffeic acid in MMMC, and to syringic acid in HMMC preparations. HMMC-associated polyamines appear in both acid-soluble and -insoluble fractions. Syringic acid also occurs in the LMMC preparation, but juice clarification changes it from acid-soluble to free form, and it coelutes with sucrose.

  13. 40 CFR 721.10188 - Fatty acids, tall-oil, reaction products with 4-methyl-2-pentanone and aliphatic polyamine...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty acids, tall-oil, reaction... Fatty acids, tall-oil, reaction products with 4-methyl-2-pentanone and aliphatic polyamine (generic). (a... generically as fatty acids, tall-oil, reaction products with 4-methyl-2-pentanone and aliphatic polyamine...

  14. Oral administration of deuterium-labelled polyamines to sucking rat pups : luminal uptake, metabolic fate and effects on gastrointestinal maturation

    NARCIS (Netherlands)

    Dorhout, B; van Faassen, A; van Beusekom, C M; Kingma, A W; de Hoog, E; Nagel, G T; Karrenbeld, A; Boersma, E R; Muskiet, F A

    1997-01-01

    Non-physiological amounts of oral polyamines have been reported to induce precocious gut maturation in rat pups. The aim of the present study was to investigate organ distribution and metabolic fate of orally administered stable-isotopically labelled polyamines in rat pups. Pups received tetradeuter

  15. 40 CFR 721.7260 - Polymer of poly-ethylene-polyamine and alkanediol di-gly-cidyl ether.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of poly-ethylene-polyamine and... New Uses for Specific Chemical Substances § 721.7260 Polymer of poly-ethylene-polyamine and alkanediol... chemical substance identified generically as polymer of polyethylenepolyamine and alkanediol diglycidyl...

  16. Role of polyamines and ethylene as modulators of plant senescence

    Indian Academy of Sciences (India)

    S Pandey; S A Ranade; P K Nagar; Nikhil Kumar

    2000-09-01

    Under optimal conditions of growth, senescence, a terminal phase of development, sets in after a certain physiological age. It is a dynamic and closely regulated developmental process which involves an array of changes at both physiological and biochemical levels including gene expression. A large number of biotic and abiotic factors accelerate the process. Convincing evidence suggests the involvement of polyamines (PAs) and ethylene in this process. Although the biosynthetic pathways of both PAs and ethylene are interrelated, S-adenosylmethionine (SAM) being a common precursor, their physiological functions are distinct and at times antagonistic, particularly during leaf and flower senescence and also during fruit ripening. This provides an effective means for regulation of their biosynthesis and also to understand the mechanism by which the balance between the two can be established for manipulating the senescence process. The present article deals with current advances in the knowledge of the interrelationship between ethylene and PAs during senescence which may open up new vistas of investigation for the future.

  17. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

    Science.gov (United States)

    Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

  18. Vapour pressure and enthalpy of vaporization of aliphatic poly-amines

    Energy Technology Data Exchange (ETDEWEB)

    Efimova, Anastasia A.; Emel' yanenko, Vladimir N. [Department of Physical Chemistry, University of Rostock, Dr-Lorenz-Weg 1, D-18059 Rostock (Germany); Verevkin, Sergey P., E-mail: sergey.verevkin@uni-rostock.d [Department of Physical Chemistry, University of Rostock, Dr-Lorenz-Weg 1, D-18059 Rostock (Germany); Chernyak, Yury [Huntsman Corporation, Advanced Technology Center, 8600 Gosling Road, The Woodlands, 77381 TX (United States)

    2010-03-15

    Molar enthalpies of vaporization of aliphatic poly-amines: 1,4-dimethylpiperazine [106-58-1], 1-(2-aminoethyl)-piperazine, [140-31-8], 1-(2-aminoethyl)-4-methyl-piperazine [934-98-5], and triethylenetetramine [112-24-3] were obtained from the temperature dependence of the vapour pressure measured by the transpiration method. A large number of the primary experimental results on temperature dependences of vapour pressures of the parent compounds have been collected from the literature and have been treated uniformly in order to derive vaporization enthalpies of poly-amines at the reference temperature 298.15 K. An internal consistency check was performed on enthalpy of vaporization values for poly-amines studied in this work.

  19. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  20. Three years of experience with polyamines in the high pressure steam system of a naphtha cracker

    Energy Technology Data Exchange (ETDEWEB)

    Lier, Roy van; Janssen, Gerard [SABIC Europe BV, Geleen (Netherlands). Site Improvement, Competence Center Manufacturing; Savelkoul, Jo

    2008-12-15

    The design and operation of the high pressure steam system of a naphtha cracker pose specific problems which in some cases cannot be satisfactorily resolved with conventional water/steam treatment programs. Following a decade of operational experience with polyamine products at lower pressures at the Geleen (petro)chemical site in the Netherlands, the ammonia/morpholine treatment of the 12.5 MPa steam system of one of SABIC Europe's naphtha crackers was converted to a polyamine program in November 2005. In this paper, the characteristics of the cracker's steam system are first described. Particular aspects of the conversion are then discussed. Finally, the experience gained and insights obtained into the polyamine treatment during the first three years are elaborated. (orig.)

  1. Regulation of polyamine biosynthetic activity by spermidine and spermine analogs--a novel antiproliferative strategy.

    Science.gov (United States)

    Porter, C W; Bergeron, R J

    1988-01-01

    Interference with polyamine biosynthesis by analog-mediated regulatory mechanisms represents a viable alternative to the use of specific enzyme inhibitors as an antiproliferative strategy. The approach is unique among antimetabolite approaches and is made possible by unusual characteristics inherent to the polyamines and their biosynthetic pathway. Current antitumor data obtained with these analogs provides indication of their potential usefulness as antitumor agents but, at the same time, demonstrates the need for improvement. This latter might be attained by the rational design of analogs which (a) bind more tightly at enzyme regulatory sites, (b) which are less able to substitute for natural polyamines in growth related functions and (c) which are eliminated less rapidly from tumor-bearing animals. At the same time, the continued preclinical development of available analogs might proceed most productively by targeting large cell lung carcinoma and melanoma and by examining the generality of the relationship between oncogene expression and the accompanying sensitivity to regulatory analogs.

  2. A method to refine crude cottonseed oil using non-toxic polyamine-based cationic polymers☆

    Institute of Scientific and Technical Information of China (English)

    Hailin Lin; Tom C Wedegaertner; Xiaoyun Mao; Xudong Jing; Aicardo Roa-Espinosa

    2015-01-01

    The traditional method to refine crude cottonseed oil is time-consuming and expensive. This study evaluates the effectiveness of coagulation–flocculation–sedimentation process using quaternary polyamine-based polymers in refining crude cottonseed oil. Flocculated by four commercial polyamine-based cationic polymers (SL2700, SL3000, SL4500 and SL5000) with varied molecular weight (MW) and charge density (CD) and followed by co-agulation with sodium hydroxide, crude cottonseed oil can be effectively purified. Free fatty acids, gossypol, pig-ments and trace elements are all effectively and sufficiently removed by the four polymers in a MW-and CD-dependent manner. Our results suggest that the use of polyamine-based cationic polymers may offer an effective and feasible alternative to the traditional method for crude cottonseed oil refining.

  3. Polyamines induce aggregation of LHC II and quenching of fluorescence in vitro.

    Science.gov (United States)

    Tsiavos, Theodoros; Ioannidis, Nikolaos E; Kotzabasis, Kiriakos

    2012-05-01

    Dissipation of excess excitation energy within the light-harvesting complex of Photosystem II (LHC II) is a main process in plants, which is measured as the non-photochemical quenching of chlorophyll fluorescence or qE. We showed in previous works that polyamines stimulate qE in higher plants in vivo and in eukaryotic algae in vitro. In the present contribution we have tested whether polyamines can stimulate quenching in trimeric LHC II and monomeric light-harvesting complex b proteins from higher plants. The tetramine spermine was the most potent quencher and induced aggregation of LHC II trimers, due to its highly cationic character. Two transients are evident at 100 μM and 350 μM for the fluorescence and absorbance signals of LHC II respectively. On the basis of observations within this work, some links between polyamines and the activation of qE in vivo is discussed.

  4. Commentary on: Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis.

    Science.gov (United States)

    Ramot, Yuval; Vardy, Leah A

    2013-11-01

    Polyamines are cationic amines essential for cellular proliferation. Recently, their role in hair follicle (HF) growth has started to be explored, but their exact function is still obscure. In the October issue of Experimental Dermatology, Luke et al. follow the observation that putrescine overproducing mice and hairless (HR) mutant mice show a similar clinical phenotype of hair loss and dermal cyst formation. They show that HR and putrescine form a negative regulatory feedback mechanism, which might regulate hair cycling and therefore control hair growth. This study clearly demonstrates that a strong connection exists between HR and polyamines although there are probably additional molecular pathways involved in the polyamine regulation of hair growth which remain to be discovered.

  5. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  6. Targets of polyamine dysregulation in major depression and suicide: Activity-dependent feedback, excitability, and neurotransmission.

    Science.gov (United States)

    Limon, Agenor; Mamdani, Firoza; Hjelm, Brooke E; Vawter, Marquis P; Sequeira, Adolfo

    2016-07-01

    Major depressive disorder (MDD) is a leading cause of disability worldwide characterized by altered neuronal activity in brain regions involved in the control of stress and emotion. Although multiple lines of evidence suggest that altered stress-coping mechanisms underlie the etiology of MDD, the homeostatic control of neuronal excitability in MDD at the molecular level is not well established. In this review, we examine past and current evidence implicating dysregulation of the polyamine system as a central factor in the homeostatic response to stress and the etiology of MDD. We discuss the cellular effects of abnormal metabolism of polyamines in the context of their role in sensing and modulation of neuronal, electrical, and synaptic activity. Finally, we discuss evidence supporting an allostatic model of depression based on a chronic elevation in polyamine levels resulting in self-sustained stress response mechanisms maintained by maladaptive homeostatic mechanisms.

  7. Effect of MeJA treatment on polyamine, energy status and anthracnose rot of loquat fruit.

    Science.gov (United States)

    Cao, Shifeng; Cai, Yuting; Yang, Zhenfeng; Joyce, Daryl C; Zheng, Yonghua

    2014-02-15

    The effect of methyl jasmonate (MeJA) on changes in polyamines content and energy status and their relation to disease resistance was investigated. Freshly harvested loquat fruit were treated with 10 μmol l(-1) MeJA and wound inoculated with Colletotrichum acutatum spore suspension (1.0 × 10(5) spores ml(-1)) after 24h, and then stored at 20 °C for 6 days. MeJA treatment significantly reduced decay incidence. MeJA treated fruit manifested higher contents of polyamines (putrescine, spermidine and spermine) compared with the control fruit, during storage. MeJA treatment also maintained higher levels of adenosine triphosphate, and suppressed an increase in adenosine monophosphate content in loquat fruit. These results suggest that MeJA treatment may inhibit anthracnose rot by increasing polyamine content and maintaining the energy status. Copyright © 2013. Published by Elsevier Ltd.

  8. {sup 99m}Tc-HYNIC-spermine for imaging polyamine transport system-positive tumours: preclinical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Pesnel, Sabrina [Institut de Recherche Pierre Fabre, Centre de Recherche en Oncologie Experimentale, Toulouse (France); UPS TAAM - CIPA, CNRS, Orleans (France); Guminski, Yves; Imbert, Thierry [Institut de Recherche Pierre Fabre, Division de Chimie Medicinale III, Castres (France); Pillon, Arnaud; Guilbaud, Nicolas; Kruczynski, Anna; Bailly, Christian [Institut de Recherche Pierre Fabre, Centre de Recherche en Oncologie Experimentale, Toulouse (France); Lerondel, Stephanie [UPS TAAM - CIPA, CNRS, Orleans (France); Le Pape, Alain [UPS TAAM - CIPA, CNRS, Orleans (France); Universite Francois Rabelais, INSERM U618, Tours (France)

    2011-10-15

    F14512 exploiting the polyamine transport system (PTS) for tumour cell delivery has been described as a potent antitumour agent. The optimal use of this compound will require a probe to identify tumour cells expressing a highly active PTS that might be more sensitive to the treatment. The aim of this study was to design and characterize a scintigraphic probe to evaluate its uptake in cancer cells expressing the PTS. Three polyamines coupled to a hydrazinonicotinamide (HYNIC) moiety were synthesized and labelled with {sup 99m}Tc. Their radiochemical purity was determined by HPLC. The plasma stability of the {sup 99m}Tc-HYNIC-spermine probe and its capacity to accumulate into PTS-active cells were also evaluated. In vitro internalization was tested using murine melanoma B16/F10 cells and human lung carcinoma A549 cells. Biodistribution was determined in healthy mice and tumour uptake was studied in B16/F10 tumour-bearing mice. A HL-60-Luc human leukaemia model was used to confront single photon emission computed tomography (SPECT) images obtained with the {sup 99m}Tc-labelled probe with those obtained by bioluminescence. The {sup 99m}Tc-HYNIC-spermine probe was selected for its capacity to accumulate into PTS-active cells and its stability in plasma. In vitro studies demonstrated that the probe was internalized in the cells via the PTS. In vivo measurements indicated a tumour to muscle scintigraphic ratio of 7.9{+-}2.8. The combined bioluminescence and scintigraphic analyses with the leukaemia model demonstrated that the spermine conjugate accumulates into the tumour cells. The {sup 99m}Tc-HYNIC-spermine scintigraphic probe is potentially useful to characterize the PTS activity of tumours. Additional work is needed to determine if this novel conjugate may be useful to analyse the PTS status of patients with solid tumours. (orig.)

  9. Polyamine biosynthesis in rice cultivars under salt stress and comparison with observations under drought stress

    Directory of Open Access Journals (Sweden)

    Phuc Thi Do

    2014-05-01

    Full Text Available Soil salinity affects a large proportion of rural area and limits agricultural productivity. To investigate differential adaptation to soil salinity, we studied salt tolerance of 18 varieties of Oryza sativa using a hydroponic culture system. Based on visual inspection and photosynthetic parameters, cultivars were classified according to their tolerance level. Additionally, biomass parameters were correlated with salt tolerance. Polyamines have frequently been demonstrated to be involved in plant stress responses and therefore soluble leaf polyamines were measured. Under salinity, putrescine (Put content was unchanged or increased in tolerant, while dropped in sensitive cultivars. Spermidine (Spd content was unchanged at lower NaCl concentrations in all, while reduced at 100 mM NaCl in sensitive cultivars. Spermine (Spm content was increased in all cultivars. A comparison with data from 21 cultivars under long-term, moderate drought stress revealed an increase of Spm under both stress conditions. While Spm became the most prominent polyamine under drought, levels of all three polyamines were relatively similar under salt stress. Put levels were reduced under both, drought and salt stress, while changes in Spd were different under drought (decrease or salt (unchanged conditions. Regulation of polyamine metabolism at the transcript level during exposure to salinity was studied for genes encoding enzymes involved in the biosynthesis of polyamines and compared to expression under drought stress. Based on expression profiles, investigated genes were divided into generally stress-induced genes (ADC2, SPD/SPM2, SPD/SPM3, one generally stress-repressed gene (ADC1, constitutively expressed genes (CPA1, CPA2, CPA4, SAMDC1, SPD/SPM1, specifically drought-induced genes (SAMDC2, AIH, one specifically drought-repressed gene (CPA3 and one specifically salt-stress repressed gene (SAMDC4, revealing both overlapping and specific stress responses under these

  10. Depleting depletion: Polymer swelling in poor solvent mixtures

    Science.gov (United States)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  11. Polyamines regulate cell growth and cellular methylglyoxal in high-glucose medium independently of intracellular glutathione.

    Science.gov (United States)

    Kwak, Min-Kyu; Lee, Mun-Hyoung; Park, Seong-Jun; Shin, Sang-Min; Liu, Rui; Kang, Sa-Ouk

    2016-03-01

    Polyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine-deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high-glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation.

  12. Effect of sulphite ions on the proline and polyamine content in the bean Phaseolus vulgaris

    Directory of Open Access Journals (Sweden)

    Piotr Karolewski

    2014-02-01

    Full Text Available The influence of sulphite (0.0125-0.2% on changes in the levels of free proline, protein bound proline and hydroxyproline and of free polyamines in the roots and leaves of two cultivars of beans (Phaseolus vulgaris differing in sensitivity to these ions was investigated. It was found that both cultivars reacted similarily, the response of the seedlings of the more sensitive cultivar occuring at lower concentrations of sulphite.The observed changes in the content of imino acids and polyamines are discussed.

  13. Natural polyamines inhibit soybean (Glycine max) lipoxygenase-1, but not the lipoxygenase-2 isozyme.

    Science.gov (United States)

    Maccarrone, M; Baroni, A; Finazzi-Agrò, A

    1998-08-01

    Natural polyamines are shown to inhibit dioxygenase activity of soybean lipoxygenase-1, but they were ineffective toward the lipoxygenase-2 isozyme. The inhibitory power was dependent on the number of basic groups in the molecule, in the order spermine > spermidine > cadaverine >/= putrescine. Both spermidine and spermine acted as uncompetitive inhibitors of lipoxygenase-1 with respect to linoleic acid, the inhibition constants being 2.70 and 0.80 mM, respectively. The inhibitory power apparently correlated with the radical-trapping ability of the polyamines. Spermidine and spermine also inhibited the co-oxidase and peroxidase activities of lipoxygenase-1 and were effective inhibitors of lipoxygenase activity in lentil root protoplasts.

  14. Macrocyclic polyamine-functionalized silica as a solid-phase extraction material coupled with ionic liquid dispersive liquid-liquid extraction for the enrichment of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Liu, Longhui; He, Lijun; Jiang, Xiuming; Zhao, Wenjie; Xiang, Guoqiang; Anderson, Jared L

    2014-04-01

    In this study, silica modified with a 30-membered macrocyclic polyamine was synthesized and first used as an adsorbent material in SPE. The SPE was further combined with ionic liquid (IL) dispersive liquid-liquid microextraction (DLLME). Five polycyclic aromatic hydrocarbons were employed as model analytes to evaluate the extraction procedure and were determined by HPLC combined with UV/Vis detection. Acetone was used as the elution solvent in SPE as well as the dispersive solvent in DLLME. The enrichment of analytes was achieved using the 1,3-dibutylimidazolium bis[(trifluoromethyl)sulfonyl]imide IL/acetone/water system. Experimental conditions for the overall macrocycle-SPE-IL-DLLME method, such as the amount of adsorbent, sample solution volume, sample solution pH, type of elution solvent as well as addition of salt, were studied and optimized. The developed method could be successfully applied to the analysis of four real water samples. The macrocyclic polyamine offered higher extraction efficiency for analytes compared with commercially available C18 cartridge, and the developed method provided higher enrichment factors (2768-5409) for model analytes compared with the single DLLME. Good linearity with the correlation coefficients ranging from 0.9983 to 0.9999 and LODs as low as 0.002 μg/L were obtained in the proposed method.

  15. Rotational Mixing and Lithium Depletion

    CERN Document Server

    Pinsonneault, M H

    2010-01-01

    I review basic observational features in Population I stars which strongly implicate rotation as a mixing agent; these include dispersion at fixed temperature in coeval populations and main sequence lithium depletion for a range of masses at a rate which decays with time. New developments related to the possible suppression of mixing at late ages, close binary mergers and their lithium signature, and an alternate origin for dispersion in young cool stars tied to radius anomalies observed in active young stars are discussed. I highlight uncertainties in models of Population II lithium depletion and dispersion related to the treatment of angular momentum loss. Finally, the origins of rotation are tied to conditions in the pre-main sequence, and there is thus some evidence that enviroment and planet formation could impact stellar rotational properties. This may be related to recent observational evidence for cluster to cluster variations in lithium depletion and a connection between the presence of planets and s...

  16. Charge depletion in organic heterojunction

    Science.gov (United States)

    Ng, T. W.; Lo, M. F.; Lee, S. T.; Lee, C. S.

    2012-03-01

    Until now two types of organic-organic heterojunction (OHJ) have been observed in P-N junctions formed between undoped-organic semiconductors. Charge-transfers across OHJs are either negligible or showing electron transfer from P-type to N-type materials, leading to charges accumulation near the interface. Here, we observed that junction of 4,4',4''-tris(2-methylphenyl-phenylamino)triphenylamine (m-MTDATA)/bathocuproine (BCP) show the third-behavior. Electrons in BCP (N-type) transfer to m-MTDATA (P-type), leading to depletion of mobile majority carriers near the junction. While "depletion junctions" are typical in inorganic semiconductors, there are no reports in undoped-OHJ. Formation mechanism of depletion OHJs and fundamental differences between inorganic and organic HJs are discussed.

  17. Correlation of endogenous free polyamine levels with root nodule senescence in different genotypes in Vigna mungo L.

    Science.gov (United States)

    Lahiri, Kajari; Chattopadhyay, Soumen; Ghosh, Bharati

    2004-05-01

    Endogenous free polyamines, nitrogenase (EC 1.1.8.6.1, acetylene reduction), and leghaemoglobin (pyridine-hemochrome assay) levels were compared among five genotypes of developing Vigna root nodules grown under field conditions. Nitrogenase activity and leghaemoglobin level attained a peak at the flowering stage and gradually declined thereafter. Individual and total polyamine also followed the same pattern. Ranking on the basis of legume yield and other morphometric attributes was PDU-2 > UH-28 > UH-82 > T-9 > Sardhomash. Except spermine, the levels of putrescine, spermidine, and total polyamine showed significant differences (p<0.05) amongst the genotypes, particularly from flowering to mid-pod development stage. Genotype, development stage, and their interaction between the two had significant (p<0.01) effects on individual as well as total polyamines. Moreover, significant high linear correlations were found between total free polyamine and putrescine with conventional nodule senescence marker like nitrogenase (R2 = 0.94 and R2 = 0.92, respectively). Putrescine had an overall positive correlation with high legume yield. The results strongly suggest a relationship between polyamine and nodule senescence. Endogenous free polyamine and putrescine may be considered as genotypic markers for nodule senescence in field grown V. mungo. It is suggested that the flowering stage is more suitable for selection.

  18. Transcriptome Analysis of Scrippsiella trochoidea CCMP 3099 Reveals Physiological Changes Related to Nitrate Depletion

    Directory of Open Access Journals (Sweden)

    Joshua Thomas Cooper

    2016-05-01

    Full Text Available Dinoflagellates are a major component of marine phytoplankton and many species are recognized for their ability to produce harmful algal blooms (HABs. Scrippsiella trochoidea is a non-toxic, marine dinoflagellate that can be found in both cold and tropic waters where it is known to produce red tide events. Little is known about the genomic makeup of S. trochoidea and a transcriptome study was conducted to shed light on the biochemical and physiological adaptations related to nutrient depletion. Cultures were grown under N and P limiting conditions and transcriptomes were generated via RNAseq technology. De novo assembly reconstructed 107,415 putative transcripts of which only 41% could be annotated. No significant transcriptomic response was observed in response to initial P depletion, however, a strong transcriptional response to N depletion was detected. Among the down-regulated pathways were those for glutamine/glutamate metabolism as well as urea and nitrate/nitrite transporters. Transcripts for ammonia transporters displayed both up- and down-regulation, perhaps related to a shift to higher affinity transporters. Genes for the utilization of DON compounds were up-regulated. These included transcripts for amino acids transporters, polyamine oxidase, and extracellular proteinase and peptidases. N depletion also triggered down regulation of transcripts related to the production of Photosystems I & II and related proteins. These data are consistent with a metabolic strategy that conserves N, while maximizing sustained metabolism by emphasizing the relative contribution of organic N sources. Surprisingly, the transcriptome also contained transcripts potentially related to secondary metabolite production, including a homolog to the Short Isoform Saxitoxin gene (sxtA from Alexandrium fundyense, which was significantly up-regulated under N-depletion. A total of 113 unique hits to Sxt genes, covering 17 of the 34 genes found in C. raciborskii were

  19. Polyamine metabolism in ripening tomato fruit. II. Polyamine metabolism and synthesis in relation to enhanced putrescine content and storage life of alc tomato fruit

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, R.; Davies, P.J. (Cornell Univ., Ithaca, NY (United States))

    1991-01-01

    The fruit of the Alcobaca landrace of tomato (Lycopersicon esculentum Mill.) have prolonged keeping qualities (determined by the allele alc) and contain three times as much putrescine as the standard Rutgers variety (Alc) at the ripe stage. Polyamine metabolism and biosynthesis were compared in fruit from Rutgers and Rutgers-alc-a near isogenic line possessing the allele alc, at four different stages of ripening. The levels of soluble polyamine conjugates as well as wall bound polyamines in the pericarp tissue and jelly were very low or nondetectable in both genotypes. The increase in putrescine content in alc pericarp is not related to normal ripening as it occurred with time and whether or not the fruit ripened. Pericarp discs of both normal and alc fruit showed a decrease in the metabolism of (1,4-{sup 14}C)putrescine and (terminal labeled-{sup 3}H)spermidine with ripening, but there were no significant differences between the two genotypes. The activity of ornithine decarboxylase was similar in the fruit pericarp of the two lines. Arginine decarboxylase activity decreased during ripening in Rutgers but decreased and rose again in Rutgers-alc fruit, and as a result it was significantly higher in alc fruit than in the normal fruit at the ripe stage. The elevated putrescine levels in alc fruit appear, therefore, to be due to an increase in the activity of arginine decarboxylase.

  20. The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis.

    Science.gov (United States)

    Koponen, Taina; Cerrada-Gimenez, Marc; Pirinen, Eija; Hohtola, Esa; Paananen, Jussi; Vuohelainen, Susanna; Tusa, Maija; Pirnes-Karhu, Sini; Heikkinen, Sami; Virkamäki, Antti; Uimari, Anne; Alhonen, Leena; Laakso, Markku

    2012-02-01

    The mitochondrial biogenesis and energy expenditure regulator, PGC-1α, has been previously reported to be induced in the white adipose tissue (WAT) and liver of mice overexpressing spermidine/spermine N (1)-acetyltransferase (SSAT). The activation of PGC-1α in these mouse lines leads to increased number of mitochondria, improved glucose homeostasis, reduced WAT mass and elevated basal metabolic rate. The constant activation of polyamine catabolism produces a futile cycle that greatly reduces the ATP pools and induces 5'-AMP-activated protein kinase (AMPK), which in turn activates PGC-1α in WAT. In this study, we have investigated the effects of activated polyamine catabolism on the glucose and energy metabolisms when targeted to specific tissues. For that we used a mouse line overexpressing SSAT under the endogenous SSAT promoter, an inducible SSAT overexpressing mouse model using the metallothionein I promoter (MT-SSAT), and a mouse model with WAT-specific SSAT overexpression (aP2-SSAT). The results demonstrated that WAT-specific SSAT overexpression was sufficient to increase the number of mitochondria, reduce WAT mass and protect the mice from high-fat diet-induced obesity. However, the improvement in the glucose homeostasis is achieved only when polyamine catabolism is enhanced at the same time in the liver and skeletal muscle. Our results suggest that the tissue-specific targeting of activated polyamine catabolism may reveal new possibilities for the development of drugs boosting mitochondrial metabolism and eventually for treatment of obesity and type 2 diabetes.

  1. 40 CFR 721.6200 - Fatty acid polyamine condensate, phosphoric acid ester salts.

    Science.gov (United States)

    2010-07-01

    ..., phosphoric acid ester salts. 721.6200 Section 721.6200 Protection of Environment ENVIRONMENTAL PROTECTION... ester salts. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified as fatty acid polyamine condensate, phosphate ester salts (PMNs P-90-1984 and...

  2. Detection of fully refocused polyamine spins in prostate cancer at 7 T.

    NARCIS (Netherlands)

    Klomp, D.W.J.; Scheenen, T.W.J.; Arteaga, C.S.; Asten, J.J.A. van; Boer, V.O.; Luijten, P.R.

    2011-01-01

    (1)H MRSI is often used at 1.5 or 3 T to study prostate cancer, where the ratio of choline + creatine to citrate is taken as a marker for tumour presence. Recently, the level of polyamines (mainly spermine) has been shown to improve specificity even further. However, the in vivo detection of these p

  3. Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1

    Directory of Open Access Journals (Sweden)

    Matthew Locke

    2016-08-01

    Full Text Available Argininosuccinate synthase 1 (ASS1 is the rate-limiting enzyme for arginine biosynthesis. ASS1 expression is lost in a range of tumor types, including 50% of malignant pleural mesotheliomas. Starving ASS1-deficient cells of arginine with arginine blockers such as ADI-PEG20 can induce selective lethality and has shown great promise in the clinical setting. We have generated a model of ADI-PEG20 resistance in mesothelioma cells. This resistance is mediated through re-expression of ASS1 via demethylation of the ASS1 promoter. Through coordinated transcriptomic and metabolomic profiling, we have shown that ASS1-deficient cells have decreased levels of acetylated polyamine metabolites, together with a compensatory increase in the expression of polyamine biosynthetic enzymes. Upon arginine deprivation, polyamine metabolites are decreased in the ASS1-deficient cells and in plasma isolated from ASS1-deficient mesothelioma patients. We identify a synthetic lethal dependence between ASS1 deficiency and polyamine metabolism, which could potentially be exploited for the treatment of ASS1-negative cancers.

  4. Hydrogen peroxide and polyamines act as double edged swords in plant abiotic stress responses

    Directory of Open Access Journals (Sweden)

    Kamala Gupta

    2016-09-01

    Full Text Available The specific genetic changes through which plants adapt to the multitude of environmental stresses are possible because of the molecular regulations in the system. These intricate regulatory mechanisms once unveiled will surely raise interesting questions. Polyamines and hydrogen peroxide have been suggested to be important signalling molecules during biotic and abiotic stresses. Hydrogen peroxide plays a versatile role from orchestrating physiological processes to stress response. It helps to achieve acclimatization and tolerance to stress by coordinating intra-cellular and systemic signalling systems. Polyamines, on the other hand, are low molecular weight polycationic aliphatic amines, which have been implicated in various stress responses. It is quite interesting to note that both hydrogen peroxide and polyamines have a fine line of inter-relation between them since the catabolic pathways of the latter releases hydrogen peroxide. In this review we have tried to illustrate the roles and their multifaceted functions of these two important signalling molecules based on current literature. This review also highlights the fact that over accumulation of hydrogen peroxide and polyamines can be detrimental for plant cells leading to toxicity and pre-mature cell death.

  5. Developmental and polyamine metabolism alterations in Rhinella arenarum embryos exposed to the organophosphate chlorpyrifos.

    Science.gov (United States)

    Sotomayor, Verónica; Lascano, Cecilia; de D'Angelo, Ana María Pechen; Venturino, Andrés

    2012-09-01

    Organophosphorus pesticides (OPs) are widely applied in the Alto Valle of Río Negro and Neuquén, Argentina, due to intensive fruit growing. Amphibians are particularly sensitive to environmental pollution, and OPs may transiently accumulate in ponds and channels of the region during their reproductive season. Organophosphorus pesticide exposure may alter amphibian embryonic development and the reproductive success of autochthonous species. In the present study, embryos of the common toad Rhinella arenarum were employed to assess developmental alterations and to study polyamine metabolism, which is essential to normal growth, as a possible target underlying the effects of the OP chlorpyrifos. As the duration of chlorpyrifos exposure increased and embryonic development progressed, the median lethal concentration (LC50) values decreased, and the percentage of malformed embryos increased. Developmental arrest was also observed and several morphological alterations were recorded, such as incomplete and abnormal closure of the neural tube, dorsal curvature of the caudal fin, reduction of body size and caudal fin length, atrophy, and edema. An early decrease in ornithine decarboxylase (ODC) activity and polyamine levels was also observed in embryos exposed to chlorpyrifos. The decrease in polyamine contents in tail bud embryos might be a consequence of the reduction in ODC activity. The alteration of polyamine metabolism occurred before embryonic growth was interrupted and embryonic malformations were observed and may be useful as a biomarker in environmental studies.

  6. Polyamine sharing between tubulin dimers favours microtubule nucleation and elongation via facilitated diffusion.

    Directory of Open Access Journals (Sweden)

    Alain Mechulam

    2009-01-01

    Full Text Available We suggest for the first time that the action of multivalent cations on microtubule dynamics can result from facilitated diffusion of GTP-tubulin to the microtubule ends. Facilitated diffusion can promote microtubule assembly, because, upon encountering a growing nucleus or the microtubule wall, random GTP-tubulin sliding on their surfaces will increase the probability of association to the target sites (nucleation sites or MT ends. This is an original explanation for understanding the apparent discrepancy between the high rate of microtubule elongation and the low rate of tubulin association at the microtubule ends in the viscous cytoplasm. The mechanism of facilitated diffusion requires an attraction force between two tubulins, which can result from the sharing of multivalent counterions. Natural polyamines (putrescine, spermidine, and spermine are present in all living cells and are potent agents to trigger tubulin self-attraction. By using an analytical model, we analyze the implication of facilitated diffusion mediated by polyamines on nucleation and elongation of microtubules. In vitro experiments using pure tubulin indicate that the promotion of microtubule assembly by polyamines is typical of facilitated diffusion. The results presented here show that polyamines can be of particular importance for the regulation of the microtubule network in vivo and provide the basis for further investigations into the effects of facilitated diffusion on cytoskeleton dynamics.

  7. Polyamine Accumulation in Transgenic Tomato Enhances the Tolerance to High Temperature Stress

    Institute of Scientific and Technical Information of China (English)

    Lin Cheng; Yijing Zou; Shuli Ding; Jiajing Zhang; Xiaolin Yu; Jiashu Cao; Gang Lu

    2009-01-01

    Polyamines play an important role in plant response to abiotic stress. S-adenosyl-I-methionine decarboxylase (SAMDC) is one of the key regulatory enzymes in the biosynthesis of polyamines. In order to better understand the effect of regulation of polyamine biosynthesis on the tolerance of high-temperature stress in tomato, SAMDC Cdna isolated from Saccharomyces cerevisiae was introduced into tomato genome by means of Agrobacterium tumefaciens through leaf disc transformation. Transgene and expression was confirmed by Southern and Northern blot analyses, respectively. Transgenic plants expressing yeast SAMDC produced 1.7- to 2.4-fold higher levels of spermidine and spermine than wild-type plants under high temperature stress, and enhanced antioxidant enzyme activity and the protection of membrane lipid peroxidation was also observed. This subsequently improved the efficiency of CO2 assimilation and protected the plants from high temperature stress, which indicated that the transgenic tomato presented an enhanced tolerance to high temperature stress (38℃) compared with wild-type plants, Our results demonstrated clearly that increasing polyamine biosynthesis in plants may be a means of creating high temperature-tolerant germplasm.

  8. Inhibition of AMPA Receptors by Polyamine Toxins is Regulated by Agonist Efficacy and Stargazin

    DEFF Research Database (Denmark)

    Poulsen, Mette H; Lucas, Simon; Strømgaard, Kristian

    2014-01-01

    The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are glutamate-gated cation channels mediating the majority of fast excitatory synaptic transmission in the central nervous system (CNS). Polyamine toxins derived from spiders and wasps are use- and voltage-dependent chan...

  9. Surface modification of an epoxy resin with polyamines and polydopamine: Adhesion toward electroless deposited copper

    Energy Technology Data Exchange (ETDEWEB)

    Schaubroeck, David, E-mail: David.Schaubroeck@elis.ugent.be [Center for Microsystems Technology (CMST), IMEC and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium); Mader, Lothar [Center for Microsystems Technology (CMST), IMEC and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium); Dubruel, Peter [Polymer Chemistry and Biomaterials Research Group, Ghent University, Krijgslaan 281 S4 bis, B-9000 Ghent (Belgium); Vanfleteren, Jan [Center for Microsystems Technology (CMST), IMEC and Ghent University, Technologiepark 914A, B-9052 Ghent (Belgium)

    2015-10-30

    Highlights: • Surface modifications of epoxy resins with polydopamine and grafted polyamines can significantly increase the adhesion toward electroless deposited copper. • A clear characterization of the copper/epoxy interphase is provided by SEM analyses of cross sections. • Tailored conditions such as etching time (roughness) and electroless deposition temperature are needed to increase the adhesion of the modified surfaces. - Abstract: In this paper the influence of the epoxy roughness, surface modifications and ELD (electroless copper deposition) temperatures on the adhesive strength of the copper is studied. Good adhesion at low roughness values is targeted due to their applicability in high density electronic circuits. Roughened epoxy surfaces are modified with adsorbed polyamines, polydopamine and polyamines grafted to polydopamine. Next the, adhesive strength of ELD copper is determined with peel strength measurements and the interphases are examined with SEM (scanning electron microscopy). Polydopamine and polyamines grafted to polydopamine can lead to increased adhesive strength at lower roughness values compared to the non-modified samples at specific plating temperatures.

  10. Finding of primitive polyamine toxins in the venom of a joro spider, Nephila clavata.

    Science.gov (United States)

    Chiba, T; Akizawa, T; Matsukawa, M; Pan-Hou, H; Yoshioka, M

    1994-09-01

    A series of joro spider toxins, novel polyamines sharing a common moiety of 2,4-dihydroxyphenylacetyl cadaverine, have been identified using various bioassays, such as inhibition of a glutamatergic transmission and insecticidal activity. In this paper, we tried to chemically find still unknown polyamine toxins in the venom of a joro spider, N. clavata, by several analytical methods based on the characteristics of the common moiety. An aqueous extract from 3000 venoms was separated by preparative high performance liquid chromatography (HPLC). The polyamine toxins were detected by monitoring the fluorescence produced in an on-line reaction of o-phthalaldehyde with amino groups and UV absorption of the phenol group. Two compounds in minute quantity were purified and analyzed by gas-liquid chromatography (GC) and HPLC, which we specifically developed for the simultaneous determination of amino acids and polyamines of the toxins. Judging from the constituents of the hydrolysate by GC and HPLC and the molecular weights determined by fast atom bombardment mass spectrometry, the two compounds were estimated to be N-(2,4-dihydroxyphenylacetyl-L-asparaginyl)-N'- (3-aminopropyl-beta-alanyl) cadaverine and N-(4-hydroxyphenylacetyl-L-asparaginyl)-N'-(3-aminopropyl-beta-ala nyl) cadaverine. These compounds were small in content and molecular weight compared with hitherto known toxins. Both were presumed to be biochemically primitive toxins and were named spidamine and joramine, respectively.

  11. Detection of fully refocused polyamine spins in prostate cancer at 7 T.

    NARCIS (Netherlands)

    Klomp, D.W.J.; Scheenen, T.W.J.; Arteaga, C.S.; Asten, J.J.A. van; Boer, V.O.; Luijten, P.R.

    2011-01-01

    (1)H MRSI is often used at 1.5 or 3 T to study prostate cancer, where the ratio of choline + creatine to citrate is taken as a marker for tumour presence. Recently, the level of polyamines (mainly spermine) has been shown to improve specificity even further. However, the in vivo detection of these p

  12. Changes in free polyamines and related enzymes during stipule and pod wall development in Pisum sativum.

    Science.gov (United States)

    Chattopadhyay, Soumen; Lahiri, Kajari; Bharati, Ghosh

    2002-08-01

    Level of free polyamines, their key metabolic enzymes, and other features related to ageing were examined during stipule and pod wall development in pea (Pisum sativum). Free polyamine titre (per unit fresh mass) in both the organs, the specific activities of arginine decarboxylase and ornithine decarboxylase in the pod wall, gradually decreased with maturation. In stipule, these enzymes attained peak activity at 15 days after pod emergence and declined thereafter. Ornithine decarboxylase activity was greater in pod wall than in stipule; while, arginine decarboxylase activity was higher in stipule. Activity of degradative enzyme diamine oxidase increased with the onset of senescence in both the organs. Chlorophyll and electrical conductance had a inverse relationship throughout the experimental period, whereas, the chlorophyll content was directly related with polyamine levels in both stipule and pod wall during aging. On the other hand, protein and RNA contents were positively correlated with free polyamines throughout the test period in stipule, but in the pod wall this was true only for the later stages of development.

  13. Solid-phase polyamine synthesis using piperazine and piperidine building blocks

    DEFF Research Database (Denmark)

    Olsen, Christian A; Witt, Matthias; Jaroszewski, Jerzy W;

    2003-01-01

    [reaction: see text]. Polyamines containing piperidine and piperazine moieties have been synthesized on solid support using SN2 alkylation of resin-bound secondary amines with 2-nitrobenzenesulfonates (nosylates). The effect of solvent on this alkylation was investigated. The methodology was empl...

  14. Exogenous Melatonin Improves Plant Iron Deficiency Tolerance via Increased Accumulation of Polyamine-Mediated Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Cheng Zhou

    2016-10-01

    Full Text Available Melatonin has recently been demonstrated to play important roles in the regulation of plant growth, development, and abiotic and biotic stress responses. However, the possible involvement of melatonin in Fe deficiency responses and the underlying mechanisms remained elusive in Arabidopsis thaliana. In this study, Fe deficiency quickly induced melatonin synthesis in Arabidopsis plants. Exogenous melatonin significantly increased the soluble Fe content of shoots and roots, and decreased the levels of root cell wall Fe bound to pectin and hemicellulose, thus alleviating Fe deficiency-induced chlorosis. Intriguingly, melatonin treatments induced a significant increase of nitric oxide (NO accumulation in roots of Fe-deficient plants, but not in those of polyamine-deficient (adc2-1 and d-arginine-treated plants. Moreover, the melatonin-alleviated leaf chlorosis was blocked in the polyamine- and NO-deficient (nia1nia2noa1 and c-PTIO-treated plants, and the melatonin-induced Fe remobilization was largely inhibited. In addition, the expression of some Fe acquisition-related genes, including FIT1, FRO2, and IRT1 were significantly up-regulated by melatonin treatments, whereas the enhanced expression of these genes was obviously suppressed in the polyamine- and NO-deficient plants. Collectively, our results provide evidence to support the view that melatonin can increase the tolerance of plants to Fe deficiency in a process dependent on the polyamine-induced NO production under Fe-deficient conditions.

  15. Polyamine catabolism is involved in response to salt stress in soybean hypocotyls.

    Science.gov (United States)

    Campestre, María Paula; Bordenave, Cesar Daniel; Origone, Andrea Cecilia; Menéndez, Ana Bernardina; Ruiz, Oscar Adolfo; Rodríguez, Andrés Alberto; Maiale, Santiago Javier

    2011-07-15

    The possible relationship between polyamine catabolism mediated by copper-containing amine oxidase and the elongation of soybean hypocotyls from plants exposed to NaCl has been studied. Salt treatment reduced values of all hypocotyl growth parameters. In vitro, copper-containing amine oxidase activity was up to 77-fold higher than that of polyamine oxidase. This enzyme preferred cadaverine over putrescine and it was active even under the saline condition. On the other hand, saline stress increased spermine and cadaverine levels, and the in vivo copper-containing amine oxidase activity in the elongation zone of hypocotyls. The last effect was negatively modulated by the addition of the copper-containing amine oxidase inhibitor N,N'-diaminoguanidine. In turn, plants treated with the inhibitor showed a significant reduction of reactive oxygen species in the elongation zone, even in the saline situation. In addition, plants grown in cadaverine-amended culture medium showed increased hypocotyl length either in saline or control conditions and this effect was also abolished by N,N'-diaminoguanidine. Taken together, our results suggest that the activity of the copper-containing amine oxidase may be partially contributing to hypocotyl growth under saline stress, through the production of hydrogen peroxide by polyamine catabolism and reinforce the importance of polyamine catabolism and hydrogen peroxide production in the induction of salt tolerance in plants.

  16. Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells.

    Science.gov (United States)

    Carnésecchi, Stéphanie; Schneider, Yann; Lazarus, Sheryl A; Coehlo, David; Gossé, Francine; Raul, Francis

    2002-01-25

    The effects of cocoa powder and extracts with different amounts of flavanols and related procyanidin oligomers were investigated on the growth of Caco-2 cells. Treatment of the cells with 50 microg/ml of procyanidin-enriched (PE) extracts caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis. This led to a decrease in the intracellular pool of the polyamines. These observations indicate that polyamine metabolism might be an important target in the anti-proliferative effects of cocoa polyphenols.

  17. Improvement of the analysis of dansylated derivatives of polyamines and their conjugates by high-performance liquid chromatography.

    Science.gov (United States)

    Fontaniella, B; Mateos, J L; Vicente, C; Legaz, M E

    2001-06-15

    The paper described a method for improving the hydrolysis of conjugated polyamines in PH fraction, isolated from the lichen Evernia prunastri, as well as the optimization of dansylation procedure of these polyamines on the basis of the pH value to which derivatization is achieved. Dansylated polyamines have been later separated by high-performance liquid chromatography (HPLC) using a gradient elution. Hydrolysis of conjugates requires acid treatment at room temperature rather than at 110 degrees C, as usually described. Dansylation is improved at high pH values, whereas removal of phenolics (mainly evernic acid), from the conjugates requires low pH values.

  18. Impact of mineral resource depletion

    CSIR Research Space (South Africa)

    Brent, AC

    2006-09-01

    Full Text Available In a letter to the editor, the authors comment on BA Steen's article on "Abiotic Resource Depletion: different perceptions of the problem with mineral deposits" published in the special issue of the International Journal of Life Cycle Assessment...

  19. Global depletion of groundwater resources

    NARCIS (Netherlands)

    Wada, Y.; Beek, L.P.H. van; van Kempen, C.M.; Reckman, J.W.T.M.; Vasak, S.; Bierkens, M.F.P.

    2010-01-01

    In regions with frequent water stress and large aquifer systems groundwater is often used as an additional water source. If groundwater abstraction exceeds the natural groundwater recharge for extensive areas and long times, overexploitation or persistent groundwater depletion occurs. Here we provid

  20. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    Science.gov (United States)

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  1. Abnormal polyamine metabolism in hereditary muscular dystrophies: effect of human growth hormone.

    Science.gov (United States)

    Rudman, D; Kutner, M H; Chawla, R K; Goldsmith, M A

    1980-01-01

    Previous studies showed hyperre-sponsiveness to human growth hormone (hGH) in men with myotonic or limb girdle dystrophies (MMD or LGD). Because polyamines may mediate some actions of hGH, we have now investigated polyamine metabolism in these and other dystrophies. Under metabolic balance study conditions, serum and urine levels of putrescine (Pu), spermidine (Sd), spermine (Sm), and cadaverine (Cd) were measured in six normal men (36-44 yr), four men with MMD (38-44 yr), and three men with LGD (30-36 yr), before and during treatment with 0.532 U/kg body wt ((3/4)/d) of hGH. Daily balances of N, P, and K were also monitored. In the normal subjects, hGH did not influence elemental balances or serum and urine polyamines. In MMD, hGH caused significant retention of N, P, and K (P muscular dystrophy, age 8-13, did not differ from those in five age-matched normal boys. Skeletal muscle polyamines were measured in five men (31-40 yr) without muscle disease and in three men with LGD (30-38 yr). Average concentrations of Pu, Sd, Sm, and Cd were 46, 306, 548, and 61 nmol/g wet wt in LGD and 1, 121, 245, and 14 in the normal subjects, respectively (P muscular dystrophy and in age- and sex-matched normal controls. Pu, Sd, Sm, and Cd levels were two to three times higher than normal in muscle, but did not differ in liver, kidney, and brain. Similar findings were made in male hamsters with hereditary dystrophy and in their controls. The abnormality in hamster muscle polyamines appeared between 1 and 6 wk of age and persisted or intensified until 30 wk. These data reveal abnormalities of polyamine metabolism in men with MMD, in men with LGD, and in mice or hamsters with hereditary muscular dystrophy. The polyamine disorder could be related to dystrophic patients' hyperresponsiveness to hGH.

  2. Spatial and temporal distribution of genes involved in polyamine metabolism during tomato fruit development.

    Science.gov (United States)

    Tsaniklidis, Georgios; Kotsiras, Anastasios; Tsafouros, Athanasios; Roussos, Peter A; Aivalakis, Georgios; Katinakis, Panagiotis; Delis, Costas

    2016-03-01

    Polyamines are organic compounds involved in various biological roles in plants, including cell growth and organ development. In the present study, the expression profile, the accumulation of free polyamines and the transcript localisation of the genes involved in Put metabolism, such as Ornithine decarboxylase (ODC), Arginine decarboxylase (ADC) and copper containing Amine oxidase (CuAO), were examined during Solanum lycopersicum cv. Chiou fruit development and maturation. Moreover, the expression of genes coding for enzymes involved in higher polyamine metabolism, including Spermidine synthase (SPDS), Spermine synthase (SPMS), S-adenosylmethionine decarboxylase (SAMDC) and Polyamine oxidase (PAO), were studied. Most genes participating in PAs biosynthesis and metabolism exhibited an increased accumulation of transcripts at the early stages of fruit development. In contrast, CuAO and SPMS were mostly expressed later, during the development stages of the fruits where a massive increase in fruit volume occurs, while the SPDS1 gene exhibited a rather constant expression with a peak at the red ripe stage. Although Put, Spd and Spm were all exhibited decreasing levels in developing immature fruits, Put levels maxed late during fruit ripening. In contrast to Put both Spd and Spm levels continue to decrease gradually until full ripening. It is worth noticing that in situ RNA-RNA hybridisation is reported for the first time in tomato fruits. The localisation of ADC2, ODC1 and CuAO gene transcripts at tissues such as the locular parenchyma and the vascular bundles fruits, supports the theory that all genes involved in Put biosynthesis and catabolism are mostly expressed in fast growing tissues. The relatively high expression levels of CuAO at the ImG4 stage of fruit development (fruits with a diameter of 3 cm), mature green and breaker stages could possibly be attributed to the implication of polyamines in physiological processes taking place during fruit ripening.

  3. Effect of Spermidine Analogues on Cell Growth of Escherichia coli Polyamine Requiring Mutant MA261.

    Directory of Open Access Journals (Sweden)

    Taketo Yoshida

    Full Text Available The effects of spermidine analogues [norspermidine (NSPD, 33, spermidine (SPD, 34, homospermidine (HSPD, 44 and aminopropylcadaverine (APCAD, 35] on cell growth were studied using Escherichia coli polyamine-requiring mutant MA261. Cell growth was compared at 32°C, 37°C, and 42°C. All four analogues were taken up mainly by the PotABCD spermidine-preferential uptake system. The degree of stimulation of cell growth at 32°C and 37°C was NSPD ≥ SPD ≥ HSPD > APCAD, and SPD ≥ HSPD ≥ NSPD > APCAD, respectively. However, at 42°C, it was HSPD » SPD > NSPD > APCAD. One reason for this is HSPD was taken up effectively compared with other triamines. In addition, since natural polyamines (triamines and teteraamines interact mainly with RNA, and the structure of RNA is more flexible at higher temperatures, HSPD probably stabilized RNA more tightly at 42°C. We have thus far found that 20 kinds of protein syntheses are stimulated by polyamines at the translational level. Among them, synthesis of OppA, RpoE and StpA was more strongly stimulated by HSPD at 42°C than at 37°C. Stabilization of the initiation region of oppA and rpoE mRNA was tighter by HSPD at 42°C than 37°C determined by circular dichroism (CD. The degree of polyamine stimulation of OppA, RpoE and StpA synthesis by NSPD, SPD and APCAD was smaller than that by HSPD at 42°C. Thus, the degree of stimulation of cell growth by spermidine analogues at the different temperatures is dependent on the stimulation of protein synthesis by some components of the polyamine modulon.

  4. Involvement of Hydrogen Peroxide Generated by Polyamine Oxidative Degradation in the Development of Lateral Roots in Soybean

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to determine whether hydrogen peroxide (H2O2) generated by polyamine oxidative degradation is involved in the development of lateral roots in soybean, the length and the number of lateral roots, the activities of polyamine oxidases and diamine oxidases, and the endogenous free polyamine and H2O2 content were analyzed in soybean (Glycine max (Linn.) Merr.) main roots of 2-d-old seedlings after treatments for 2 d with exogenous β-hydroxyethylhydrazine (an inhibitor of polyamine oxidases), H2O2, putrescine, cyclohexylamine (an inhibitor of spermidine synthase) or N,N'-dimethylthiourea (a scavenger of hydrogen peroxide).β-hydroxyethylhydrazine treatment strongly inhibited the development of lateral roots in soybean seedlings,reduced the activities of polyamine oxidases and diamine oxidases, decreased H2O2 levels, and led to the accumulation of endogenous polyamines in the main roots. The inhibitory effect of β-hydroxyethylhydrazine on root development could be alleviated by exogenously applied 10 μmol/L H2O2 (a major product of polyamine oxidation). Treatment with cyclohexylamine and putrescine promoted root growth slightly, but treatment with cyclohexylamine plus N,N'-dimethylthiourea or putrescine plus N,N'-dimethylthiourea prevented the development of soybean lateral roots. The effects of these treatments on the development of soybean lateral roots were consistent with the changes in endogenous H2O2 levels. These results suggest that the development of soybean lateral roots is associated with the oxidative degradation of polyamines, and that their products,especially H2O2, are likely to play an important role in the growth of soybean lateral roots.

  5. Ozone depletion, paradigms, and politics

    Energy Technology Data Exchange (ETDEWEB)

    Iman, R.L.

    1993-10-01

    The destruction of the Earth`s protective ozone layer is a prime environmental concern. Industry has responded to this environmental problem by: implementing conservation techniques to reduce the emission of ozone-depleting chemicals (ODCs); using alternative cleaning solvents that have lower ozone depletion potentials (ODPs); developing new, non-ozone-depleting solvents, such as terpenes; and developing low-residue soldering processes. This paper presents an overview of a joint testing program at Sandia and Motorola to evaluate a low-residue (no-clean) soldering process for printed wiring boards (PWBs). Such processes are in widespread use in commercial applications because they eliminate the cleaning operation. The goal of this testing program was to develop a data base that could be used to support changes in the mil-specs. In addition, a joint task force involving industry and the military has been formed to conduct a follow-up evaluation of low-residue processes that encompass the concerns of the tri-services. The goal of the task force is to gain final approval of the low-residue technology for use in military applications.

  6. The role of hypusine depletion in cytostasis induced by S-adenosyl-L-methionine decarboxylase inhibition: new evidence provided by 1-methylspermidine and 1,12-dimethylspermine.

    Science.gov (United States)

    Byers, T L; Lakanen, J R; Coward, J K; Pegg, A E

    1994-10-15

    The abilities of the natural polyamines, spermidine and spermine, and of the synthetic analogues, 1-methylspermidine and 1,12-dimethylspermine, to reverse the effects of the S-adenosyl-L-methionine decarboxylase inhibitor 5'-([(Z)-4-aminobut-2-enyl]methylamino)-5'-deoxyadenosine (AbeAdo) on L1210-cell growth were studied. L1210 cells were exposed to AbeAdo for 12 days to induce cytostasis and then exposed to spermidine, spermine, 1-methylspermidine or 1,12-dimethylspermine in the continued presence of AbeAdo. AbeAdo-induced cytostasis was overcome by the natural polyamines, spermidine and spermine. The cytostasis was also reversed by 1-methylspermidine. 1,12-Dimethylspermine had no effect on the AbeAdo-induced cytostasis of chronically treated cells, although it was active in permitting growth of cells treated with the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine. The initial 12-day exposure to AbeAdo elevated intracellular putrescine levels, depleted intracellular spermidine and spermine, and resulted in the accumulation of unmodified eukaryotic translation initiation factor 5A (eIF-5A). Exposure of these cells to exogenous spermidine, which is the natural substrate for deoxyhypusine synthase, resulted in a decrease in the unmodified eIF-5A content. 1-Methylspermidine, which was found to be a substrate of deoxyhypusine synthase in vitro, also decreased the levels of unmodified eIF-5A in the AbeAdo-treated cells. Although spermine is not a substrate of deoxyhypusine synthase, spermine was converted into spermidine in the L1210 cells, and spermine addition to AbeAdo-treated cells resulted in the appearance of both intracellular spermine and spermidine and in the decrease in unmodified eIF-5A. Exogenous 1,12-dimethylspermine, which was not metabolized to spermine or to 1-methylspermidine and was not a substrate of deoxyhypusine synthase in vitro, did not decrease levels of unmodified eIF-5A. The finding that AbeAdo-induced cytostasis was only

  7. Silicon-mediated changes in polyamines participate in silicon-induced salt tolerance in Sorghum bicolor L.

    Science.gov (United States)

    Yin, Lina; Wang, Shiwen; Tanaka, Kiyoshi; Fujihara, Shinsuke; Itai, Akihiro; Den, Xiping; Zhang, Suiqi

    2016-02-01

    Silicon (Si) is generally considered a beneficial element for the growth of higher plants, especially under stress conditions, but the mechanisms remain unclear. Here, we tested the hypothesis that Si improves salt tolerance through mediating important metabolism processes rather than acting as a mere mechanical barrier. Seedlings of sorghum (Sorghum bicolor L.) growing in hydroponic culture were treated with NaCl (100 mm) combined with or without Si (0.83 mm). The result showed that supplemental Si enhanced sorghum salt tolerance by decreasing Na(+) accumulation. Simultaneously, polyamine (PA) levels were increased and ethylene precursor (1-aminocyclopropane-1-carboxylic acid: ACC) concentrations were decreased. Several key PA synthesis genes were up-regulated by Si under salt stress. To further confirm the role of PA in Si-mediated salt tolerance, seedlings were exposed to spermidine (Spd) or a PA synthesis inhibitor (dicyclohexylammonium sulphate, DCHA) combined with salt and Si. Exogenous Spd showed similar effects as Si under salt stress whereas exogenous DCHA eliminated Si-enhanced salt tolerance and the beneficial effect of Si in decreasing Na(+) accumulation. These results indicate that PAs and ACC are involved in Si-induced salt tolerance in sorghum and provide evidence that Si plays an active role in mediating salt tolerance.

  8. Accumulation of free polyamines enhances the antioxidant response in fruits of grafted tomato plants under water stress.

    Science.gov (United States)

    Sánchez-Rodríguez, E; Romero, L; Ruiz, J M

    2016-01-15

    Polyamines, small aliphatic polycations, have been suggested to play key roles in a number of biological processes. In this paper, attempts were made to investigate the possibility of improving antioxidant response of tomato fruits in relation with endogenous free polyamines content. We studied the reactive oxygen species and polyamines content, and antioxidant and polyamine-biosynthesis enzyme activities in fruits of ungrafted and grafted tomato plants under moderate water stress. We used a drought-tolerant cultivar (Zarina) and drought-sensitive cultivar (Josefina) to obtain reciprocal graft, selfgraft and ungraft plants. Fruits contained higher endogenous polyamine content during the course of the experiment relative to the control, coupled with higher arginine decarboxylase and spermine synthase activities in Zarina ungrafted and ZarxJos. In these cultivars, tomato fruits showed a lower reactive oxygen species generation and higher catalase and superoxide dismutase activities, suggesting that a higher content in polyamines (especially spermine) exerted a positive effect on antioxidant systems. All of these data suggest that spermine leads to more effective reactive oxygen species scavenging (less tissue damage) in tomato fruits, which may function collectively to enhance dehydration tolerance.

  9. Ultrahigh-contrast imaging by temporally modulated stimulated emission depletion

    NARCIS (Netherlands)

    Doronina-Amitonova, L.V.; Fedotov, I.V.; Zheltikov, A.M.

    2015-01-01

    Stimulated emission depletion (STED) is the key optical technology enabling super-resolution microscopy below the diffraction limit. Here, we demonstrate that modulation of STED in the time domain, combined with properly designed lock-in detection, can radically enhance the contrast of fluorescent i

  10. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Giselle L Saulnier Sholler

    Full Text Available Neuroblastoma (NB is the most common cancer in infancy and most frequent cause of death from extracranial solid tumors in children. Ornithine decarboxylase (ODC expression is an independent indicator of poor prognosis in NB patients. This study investigated safety, response, pharmacokinetics, genetic and metabolic factors associated with ODC in a clinical trial of the ODC inhibitor difluoromethylornithine (DFMO ± etoposide for patients with relapsed or refractory NB.Twenty-one patients participated in a phase I study of daily oral DFMO alone for three weeks, followed by additional three-week cycles of DFMO plus daily oral etoposide. No dose limiting toxicities (DLTs were identified in patients taking doses of DFMO between 500-1500 mg/m2 orally twice a day. DFMO pharmacokinetics, single nucleotide polymorphisms (SNPs in the ODC gene and urinary levels of substrates for the tissue polyamine exporter were measured. Urinary polyamine levels varied among patients at baseline. Patients with the minor T-allele at rs2302616 of the ODC gene had higher baseline levels (p=0.02 of, and larger decreases in, total urinary polyamines during the first cycle of DFMO therapy (p=0.003 and had median progression free survival (PFS that was over three times longer, compared to patients with the major G allele at this locus although this last result was not statistically significant (p=0.07. Six of 18 evaluable patients were progression free during the trial period with three patients continuing progression free at 663, 1559 and 1573 days after initiating treatment. Median progression-free survival was less among patients having increased urinary polyamines, especially diacetylspermine, although this result was not statistically significant (p=0.056.DFMO doses of 500-1500 mg/m2/day are safe and well tolerated in children with relapsed NB. Children with the minor T allele at rs2302616 of the ODC gene with relapsed or refractory NB had higher levels of urinary

  11. If ego depletion cannot be studied using identical tasks, it is not ego depletion.

    Science.gov (United States)

    Lange, Florian

    2015-01-01

    The hypothesis that human self-control capacities are fueled by glucose has been challenged on multiple grounds. A recent study by Lange and Eggert adds to this criticism by presenting two powerful but unsuccessful attempts to replicate the effect of sugar drinks on ego depletion. The dual-task paradigms employed in these experiments have been criticized for involving identical self-control tasks, a methodology that has been argued to reduce participants' willingness to exert self-control. The present article addresses this criticism by demonstrating that there is no indication to believe that the study of glucose effects on ego depletion should be restricted to paradigms using dissimilar acts of self-control. Failures to observe such effects in paradigms involving identical tasks pose a serious problem to the proposal that self-control exhaustion might be reversed by rinsing or ingesting glucose. In combination with analyses of statistical credibility, the experiments by Lange and Eggert suggest that the influence of sugar on ego depletion has been systematically overestimated.

  12. Ant 4,4, a polyamine-anthracene conjugate, induces cell death and recovery in human promyelogenous leukemia cells (HL-60).

    Science.gov (United States)

    Traquete, Rui; Ghani, Radiah A; Phanstiel, Otto; Wallace, Heather M

    2013-04-01

    One of the major problems in cancer therapy is the lack of specificity of chemotherapeutic agents towards cancer cells, resulting in adverse side effects. One means to counter this is to selectively deliver the drug to the cancer cell. Cancer cells accumulate increased concentrations of polyamines compared to normal cells, mainly through an increased uptake of preformed polyamines via the polyamine transport system (PTS). Furthermore, the non-stringent structural requirements of the PTS enable the transport of a range of polyamine-based molecules. Thus, the PTS can be used to transport compounds linked to polyamines selectively to cancer cells. In our laboratory, polyamine-anthracene conjugates have shown potent anti-tumour activity towards HL-60 cells. The aim of this study was to determine the cytotoxicity of Ant-4,4, a homospermidine-anthracene conjugate, and assess the long-term effects by determining whether cancer cells were able to recover from treatment. During exposure, Ant-4,4 was an effective growth-inhibitory agent in HL-60 cells decreasing viable cell number, protein and polyamine content. Evidence indicates concomitant cell-cycle arrest and increased apoptosis. Once the drug was removed, HL-60 cells recovered gradually over time. Increasing cell number, protein content and polyamine content, as well as diminished effects on cell-cycle and apoptotic stimuli were observed over time. These data suggest that, despite being an effective way of delivering anthracene, these polyamine conjugates do not exert long-lasting effects on HL-60 cells.

  13. Structure-activity relationship studies of N-methylated and N-hydroxylated spider polyamine toxins as inhibitors of ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Nørager, Niels G; Poulsen, Mette H; Jensen, Anna G

    2014-01-01

    Polyamine toxins from spiders and wasps are potent open-channel blockers of ionotropic glutamate (iGlu) receptors. It is well-established that secondary amino groups in the polyamine moiety of these toxins are key to both selectivity and potency at iGlu receptors, still some native spider polyamine...... toxins comprise both N-methyl and N-hydroxy functionalities. Here, we investigate the effect of both N-methylation and N-hydroxylation of spider polyamine toxins by the synthesis and biological evaluation of the naturally occurring N-methylated argiopinines and pseudoargiopinines I and II, N...

  14. Summer time Fe depletion in the Antarctic mesopause region

    Science.gov (United States)

    Viehl, T. P.; Höffner, J.; Lübken, F.-J.; Plane, J. M. C.; Kaifler, B.; Morris, R. J.

    2015-05-01

    We report common volume measurements of Fe densities, temperatures and ice particle occurrence in the mesopause region at Davis Station, Antarctica (69°S) in the years 2011-2012. Our observations show a strong correlation of the Fe-layer summer time depletion with temperature, but no clear causal relation with the onset or occurrence of ice particles measured as noctilucent clouds (NLC) or polar mesosphere summer echoes (PMSE). The combination of these measurements indicates that the strong summer depletion can be explained by gas-phase chemistry alone and does not require heterogeneous removal of Fe and its compounds on ice particles.

  15. The Case of Ozone Depletion

    Science.gov (United States)

    Lambright, W. Henry

    2005-01-01

    While the National Aeronautics and Space Administration (NASA) is widely perceived as a space agency, since its inception NASA has had a mission dedicated to the home planet. Initially, this mission involved using space to better observe and predict weather and to enable worldwide communication. Meteorological and communication satellites showed the value of space for earthly endeavors in the 1960s. In 1972, NASA launched Landsat, and the era of earth-resource monitoring began. At the same time, in the late 1960s and early 1970s, the environmental movement swept throughout the United States and most industrialized countries. The first Earth Day event took place in 1970, and the government generally began to pay much more attention to issues of environmental quality. Mitigating pollution became an overriding objective for many agencies. NASA's existing mission to observe planet Earth was augmented in these years and directed more toward environmental quality. In the 1980s, NASA sought to plan and establish a new environmental effort that eventuated in the 1990s with the Earth Observing System (EOS). The Agency was able to make its initial mark via atmospheric monitoring, specifically ozone depletion. An important policy stimulus in many respects, ozone depletion spawned the Montreal Protocol of 1987 (the most significant international environmental treaty then in existence). It also was an issue critical to NASA's history that served as a bridge linking NASA's weather and land-resource satellites to NASA s concern for the global changes affecting the home planet. Significantly, as a global environmental problem, ozone depletion underscored the importance of NASA's ability to observe Earth from space. Moreover, the NASA management team's ability to apply large-scale research efforts and mobilize the talents of other agencies and the private sector illuminated its role as a lead agency capable of crossing organizational boundaries as well as the science-policy divide.

  16. Retina maturation following administration of thyroxine in developing rats: effects on polyamine metabolism and glutamate decarboxylase.

    Science.gov (United States)

    Macaione, S; Di Giorgio, R M; Nicotina, P A; Ientile, R

    1984-08-01

    The effects of subcutaneous daily treatment with thyroxine on cell proliferation, differentiation, polyamines, and gamma-aminobutyric acid metabolism in the rat retina were studied during the first 20 postnatal days. The retinal layers of the treated rats displayed an enhanced cell differentiation which reached its maximum 9-12 days from birth; but this effect stopped very quickly and was finished by the 20th postnatal day. Primarily there was an increase in ornithine decarboxylase activity which was accompanied by an increase in putrescine, spermidine, and spermine levels. S-Adenosylmethionine decarboxylase was induced later than ODC; corresponding with the enhanced synaptogenesis, glutamate decarboxylase increased 15-fold between the fourth and 15th days. Our data are consistent with the hypothesis that thyroxine may exert some of its effects by inducing the enzymes which regulate polyamine metabolism and synaptogenesis.

  17. A Cross-Sectional Study: Nutritional Polyamines in Frequently Consumed Foods of the Turkish Population

    Directory of Open Access Journals (Sweden)

    Nihal Buyukuslu

    2014-10-01

    Full Text Available Putrescine, spermidine and spermine are the most abundant polycationic natural amines found in nearly all organisms. They are involved in regulation of gene expression, translation, cell proliferation and differentiation. They can be supplied by the endogenous synthesis inside the cell or by the intake from exogenous sources. There is a growing body of literature associated with the effects of bioactive amines on health and diseases, but limited information about polyamine content in foods is available. In the present study, the polyamine content of frequently consumed foods in a typical Turkish diet was estimated for adults, including tea, bread and yoghurt. The estimation of daily intake was defined as 93,057 nmol/day putrescine, 33,122 nmol/day spermidine, 13,685 nmol/day spermine. The contribution of foods to daily intake was: dairy products (47.32%, vegetables and grains (21.09% and wheat products (12.75%.

  18. Defining the role of polyamines in colon carcinogenesis using mouse models

    Directory of Open Access Journals (Sweden)

    Natalia A Ignatenko

    2011-01-01

    Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

  19. Comparative uptake of polyamines by prostate and non-prostate cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Srinath, P.; McQuarrie, S.A.; Suresh, M.R. E-mail: msuresh@pharmacy.ualberta.ca

    2002-05-01

    The Km and Vmax of [{sup 14}C]-radiolabeled polyamines were determined for PC-3 and AT3B-1 cell lines. With PC-3 Km values are in the following order: ornithine> spermidine> spermine> putrescine, while with AT3B-1 it was spermidine> ornithine> spermine> putrescine. To determine which of these polyamines exhibit higher accumulation, the relative uptake of all the four amines was studied with prostate (PC-3, AT3B-1, LNCaP) and non-prostate (MCF-7, KLN-205, OVCAR) cell lines at 10 and 20 {mu}M after 1 hour. Spermine and spermidine accumulated at higher levels in prostate (AT3B-1 and LNCaP) over non-prostate cell lines (p<0.01). Putrescine accumulated more in PC-3 and LNCaP than the non-prostate cancer cells.

  20. Polyamine stress at high pH in Escherichia coli K-12

    Directory of Open Access Journals (Sweden)

    Tate Daniel P

    2005-10-01

    Full Text Available Abstract Background Polyamines such as spermine and spermidine are required for growth of Escherichia coli; they interact with nucleic acids, and they bind to ribosomes. Polyamines block porins and decrease membrane permeability, activities that may protect cells in acid. At high concentrations, however, polyamines impair growth. They impair growth more severely at high pH, probably due to their increased uptake as membrane-permeant weak bases. The role of pH is critical in understanding polyamine stress. Results The effect of polyamines was tested on survival of Escherichia coli K-12 W3110 in extreme acid or base (pH conditions outside the growth range. At pH 2, 10 mM spermine increased survival by 2-fold, and putrescine increased survival by 30%. At pH 9.8, however, E. coli survival was decreased 100-fold by 10 mM spermine, putrescine, cadaverine, or spermidine. At pH 8.5, spermine decreased the growth rate substantially, whereas little effect was seen at pH 5.5. Spermidine required ten-fold higher concentrations to impair growth. On proteomic 2-D gels, spermine and spermidine caused differential expression of 31 different proteins. During log-phase growth at pH 7.0, 1 mM spermine induced eight proteins, including PykF, GlpK, SerS, DeaD, OmpC and OmpF. Proteins repressed included acetate-inducible enzymes (YfiD, Pta, Lpd as well as RapA (HepA, and FabB. At pH 8.5, spermine induced additional proteins: TnaA, OmpA, YrdA and NanA (YhcJ and also repressed 17 proteins. Four of the proteins that spermine induced (GlpK, OmpA, OmpF, TnaA and five that were repressed (Lpd, Pta, SucB, TpiA, YfiD show similar induction or repression, respectively, in base compared to acid. Most of these base stress proteins were also regulated by spermidine, but only at ten-fold higher concentration (10 mM at high pH (pH 8.5. Conclusion Polyamines increase survival in extreme acid, but decrease E. coli survival in extreme base. Growth inhibition by spermine and

  1. The Effects of Conformational Constraints in the Polyamine Moiety of Philanthotoxins on AMPAR Inhibition

    DEFF Research Database (Denmark)

    Franzyk, Henrik; Grzeskowiak, John W; Tikhonov, Denis B;

    2014-01-01

    Philanthotoxin-433 (PhTX-433) is a known potent inhibitor of ionotropic glutamate receptors, and analogues have been synthesised to identify more potent and selective antagonists. Herein we report the synthesis of four PhTXs with a cyclopropane moiety introduced into their polyamine chain, and th...... conformation due to enhanced intramolecular folding. Elongated PhTX-444 analogues alleviate this to some extent, but optimal positioning of the amines is not permitted....

  2. Polyamines as Snake Toxins and Their Probable Pharmacological Functions in Envenomation

    Directory of Open Access Journals (Sweden)

    Steven D. Aird

    2016-09-01

    Full Text Available While decades of research have focused on snake venom proteins, far less attention has been paid to small organic venom constituents. Using mostly pooled samples, we surveyed 31 venoms (six elapid, six viperid, and 19 crotalid for spermine, spermidine, putrescine, and cadaverine. Most venoms contained all four polyamines, although some in essentially trace quantities. Spermine is a potentially significant component of many viperid and crotalid venoms (≤0.16% by mass, or 7.9 µmol/g; however, it is almost completely absent from elapid venoms assayed. All elapid venoms contained larger molar quantities of putrescine and cadaverine than spermine, but still at levels that are likely to be biologically insignificant. As with venom purines, polyamines impact numerous physiological targets in ways that are consistent with the objectives of prey envenomation, prey immobilization via hypotension and paralysis. Most venoms probably do not contain sufficient quantities of polyamines to induce systemic effects in prey; however, local effects seem probable. A review of the pharmacological literature suggests that spermine could contribute to prey hypotension and paralysis by interacting with N-methyl-d-aspartate (NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptors, nicotinic and muscarinic acetylcholine receptors, γ-Aminobutyric acid (GABA receptors, blood platelets, ryanodine receptors, and Ca2+-ATPase. It also blocks many types of cation-permeable channels by interacting with negatively charged amino acid residues in the channel mouths. The site of envenomation probably determines which physiological targets assume the greatest importance; however, venom-induced liberation of endogenous, intracellular stores of polyamines could potentially have systemic implications and may contribute significantly to envenomation sequelae.

  3. Short Term Effect of Salt Shock on Ethylene and Polyamines Depends on Plant Salt Sensitivity

    Directory of Open Access Journals (Sweden)

    Pedro J. Zapata

    2017-05-01

    Full Text Available In the present manuscript the short term effect (3–24 h of a saline shock (NaCl 100 mM on fresh weight, water content, respiration rate, ethylene production and Na+, Cl-, ACC and polyamine concentration was studied in four plant species with different salt sensitivity, pepper, lettuce, spinach, and beetroot. Higher reduction in fresh weight and water content as a consequence of saline shock was found in pepper and lettuce plants than in spinach and beetroot, the latter behaving as more salinity tolerant. In general, salinity led to rapid increases in respiration rate, ethylene production and ACC and polyamine (putrescine, spermidine, and spermine concentrations in shoot and root. These increases were related to plant salinity sensitivity, since they were higher in the most sensitive species and vice versa. However, ethylene and respiration rates in salt stressed plants recovered similar values to controls after 24 h of treatment in salt tolerant plants, while still remaining high in the most sensitive. On the other hand, sudden increases in putrescine, spermidine, and spermine concentration were higher and occurred earlier in pepper and lettuce, the most sensitive species, than in spinach and beetroot, the less sensitive ones. These increases tended to disappear after 24 h, except in lettuce. These changes would support the conclusion that ethylene and polyamine increases could be considered as a plant response to saline shock and related to the plant species sensitivity to this stress. In addition, no competition between polyamines and ethylene biosynthesis for their common precursor was observed.

  4. Polyamines as Snake Toxins and Their Probable Pharmacological Functions in Envenomation

    Science.gov (United States)

    Aird, Steven D.; Villar Briones, Alejandro; Roy, Michael C.; Mikheyev, Alexander S.

    2016-01-01

    While decades of research have focused on snake venom proteins, far less attention has been paid to small organic venom constituents. Using mostly pooled samples, we surveyed 31 venoms (six elapid, six viperid, and 19 crotalid) for spermine, spermidine, putrescine, and cadaverine. Most venoms contained all four polyamines, although some in essentially trace quantities. Spermine is a potentially significant component of many viperid and crotalid venoms (≤0.16% by mass, or 7.9 µmol/g); however, it is almost completely absent from elapid venoms assayed. All elapid venoms contained larger molar quantities of putrescine and cadaverine than spermine, but still at levels that are likely to be biologically insignificant. As with venom purines, polyamines impact numerous physiological targets in ways that are consistent with the objectives of prey envenomation, prey immobilization via hypotension and paralysis. Most venoms probably do not contain sufficient quantities of polyamines to induce systemic effects in prey; however, local effects seem probable. A review of the pharmacological literature suggests that spermine could contribute to prey hypotension and paralysis by interacting with N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, nicotinic and muscarinic acetylcholine receptors, γ-Aminobutyric acid (GABA) receptors, blood platelets, ryanodine receptors, and Ca2+-ATPase. It also blocks many types of cation-permeable channels by interacting with negatively charged amino acid residues in the channel mouths. The site of envenomation probably determines which physiological targets assume the greatest importance; however, venom-induced liberation of endogenous, intracellular stores of polyamines could potentially have systemic implications and may contribute significantly to envenomation sequelae. PMID:27681740

  5. From biosilicification to tailored materials: Optimizing hydrophobic domains and resistance to protonation of polyamines

    OpenAIRE

    Belton, David J.; Patwardhan, Siddharth V.; Annenkov, Vadim V.; Danilovtseva, Elena N.; Perry, Carole C.

    2008-01-01

    Considerable research has been directed toward identifying the mechanisms involved in biosilicification to understand and possibly mimic the process for the production of superior silica-based materials while simultaneously minimizing pollution and energy costs. Molecules isolated from diatoms and, most recently sponges, thought to be key to this process contain polyamines with a propylamine backbone and variable levels of methylation. In a chemical approach to understanding the role of amine...

  6. Protein-polyamine conjugates by transglutaminase 2 as potential markers for antineoplastic screening of natural compounds.

    Science.gov (United States)

    Lentini, A; Provenzano, B; Tabolacci, C; Beninati, S

    2009-04-01

    The role of post-translational modification of cell proteins with polyamines, a reaction catalyzed by a tissue tranglutaminase (TG, EC 2.3.2.13), in the induction of cell differentiation, represents an intriguing strategy to control cell proliferation and metastatic ability of different tumor cell lines. In this review, we focus our attention on the metabolic aspects of some natural compounds (methylxantines, retinoids and flavonoids) responsible of their antitumor effects exerted through the induction of TG activity in cancer cells.

  7. Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning

    Science.gov (United States)

    Alberca, Lucas N.; Sbaraglini, María L.; Balcazar, Darío; Fraccaroli, Laura; Carrillo, Carolina; Medeiros, Andrea; Benitez, Diego; Comini, Marcelo; Talevi, Alan

    2016-04-01

    Chagas disease is a parasitic infection caused by the protozoa Trypanosoma cruzi that affects about 6 million people in Latin America. Despite its sanitary importance, there are currently only two drugs available for treatment: benznidazole and nifurtimox, both exhibiting serious adverse effects and limited efficacy in the chronic stage of the disease. Polyamines are ubiquitous to all living organisms where they participate in multiple basic functions such as biosynthesis of nucleic acids and proteins, proliferation and cell differentiation. T. cruzi is auxotroph for polyamines, which are taken up from the extracellular medium by efficient transporters and, to a large extent, incorporated into trypanothione (bis-glutathionylspermidine), the major redox cosubstrate of trypanosomatids. From a 268-compound database containing polyamine analogs with and without inhibitory effect on T. cruzi we have inferred classificatory models that were later applied in a virtual screening campaign to identify anti-trypanosomal compounds among drugs already used for other therapeutic indications (i.e. computer-guided drug repositioning) compiled in the DrugBank and Sweetlead databases. Five of the candidates identified with this strategy were evaluated in cellular models from different pathogenic trypanosomatids ( T. cruzi wt, T. cruzi PAT12, T. brucei and Leishmania infantum), and in vitro models of aminoacid/polyamine transport assays and trypanothione synthetase inhibition assay. Triclabendazole, sertaconazole and paroxetine displayed inhibitory effects on the proliferation of T. cruzi (epimastigotes) and the uptake of putrescine by the parasite. They also interfered with the uptake of others aminoacids and the proliferation of infective T. brucei and L. infantum (promastigotes). Trypanothione synthetase was ruled out as molecular target for the anti-parasitic activity of these compounds.

  8. SA improvement of hyperhydricity reversion in Thymus daenensis shoots culture may be associated with polyamines changes.

    Science.gov (United States)

    Hassannejad, Sahar; Bernard, Françoise; Mirzajani, Fateme; Gholami, Morteza

    2012-02-01

    In shoot cultures of Thymus daenensis, hyperhydricity syndrome promoted by benzyladenine (BA) is characterised by the development of chlorophyll-deficient shoots with a high water content and reduced growth that is less differentiated. By removing the BA from the culture medium, the hyperhydricity was reversed, and the reversion toward a normal growth in vitro was more efficient in shoots treated with 5 μM of salicylic acid (SA), showing a significant increase in chlorophyll b after 4 weeks of culture. In the present study, the effect of salicylic acid on the reversion of shoot hyperhydricity was investigated at the level of the free, soluble and insoluble conjugated polyamine content. In T. daenensis micropropagated shoots, the level of polyamines was high, with a predominance of putrescine. BA, which triggered hyperhydricity, caused a reduction of the polyamine (PA) content by one-half due to a decrease in the putrescine content and insoluble conjugated PAs that were not detected in the hyperhydric shoots. In the reverted shoots, changes of the free polyamines, spermidine and, more notably, spermine, were shown. The spermine content doubled after 4 weeks of culture, and its amount was the same as that found in normal shoots, suggesting that free spermine could be particularly involved in the reversion of hyperhydricity. In the SA-reverted tissues, the PA pattern was marked with a transient increase of free putrescine, spermidine and spermine and an enhancement of soluble conjugated spermine. This transitory SA-dependent amplification of PAs was concomitant with a remarkable transient increase of H(2)O(2), suggesting that SA may be implicated in PA signalling pathways for tissue differentiation during the reversion of hyperhydricity in T. daenensis.

  9. Structural design at the polymer surface interface in nanoporous silica polyamine composites

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Jesse; Berlin, Matthew; Hughes, Mark; Johnston, Erik; Kailasam, Varadharajan [Department of Chemistry, University of Montana, 32 Campus Drive, Missoula, MT 59812 (United States); Rosenberg, Edward, E-mail: edward.rosenberg@mso.umt.edu [Department of Chemistry, University of Montana, 32 Campus Drive, Missoula, MT 59812 (United States); Sardot, Tova; Wood, Jessica [Department of Chemistry, University of Montana, 32 Campus Drive, Missoula, MT 59812 (United States); Hart, Carolyn [Purity Systems Inc., 1121 Broadway, Missoula, MT 59812 (United States)

    2011-04-15

    Research highlights: {yields} Silica leaching rates for silica polyamine composites have been measured. {yields} The surface features of the composites with different silane anchors have been evaluated. {yields} The leaching characteristics of the composites are compared with similar materials made by the sol-gel method. {yields} Solid state NMR techniques, porosimetry and electron microscopy have been used to characterize all the materials discussed. - Abstract: The factors affecting the rate of silica leaching in alkaline aqueous media from surface silanized, nanoporous, amorphous, silica gels and from silanized silica gels that have been modified with polyamines to form the previously reported silica polyamine composites (SPCs), BP-1 and BP-2 have been investigated. Silanization with alkyl trichlorosilanes slows the rate of silica leaching relative to the unmodified silica gels. The use of bulkier aryl silanes somewhat decreases the silica leaching under the same conditions. Interestingly, after modification of the silanized silica with poly(allylamine) (PAA) to make BP-1, the leaching increases, but subsequent modification of the SPC with chloroacetic acid to make BP-2, quenches this increase. A mechanism explaining these results is discussed. Analogous composites have been prepared using sol-gel chemistry. These materials were characterized and their silica leaching properties were compared with the original BP-1. CPMAS {sup 13}C and {sup 29}Si NMR of the various surfaces have been applied to better understand the nature of the modified surfaces. Significant changes in the nature of the surface siloxanes are observed for the different matrices and on their conversion to the polyamine composite. Scanning electron microscopy and pore size distributions for the composites made from commercial silica gel and from sol-gel chemistry are also reported and compared.

  10. Polyamine Triglycerides: Synthesis and Study of Their Potential in Lubrication, Neutralization, and Sequestration.

    Science.gov (United States)

    Harry-O'kuru, Rogers E; Biresaw, Girma; Murray, Rex E

    2015-07-22

    Renewable resources have evoked a new awakening in both scientific and industrial circles in the past decade. Vegetable oil is one category of renewables that is amenable as a source of new industrial products. Because the source feedstock, seeds, are environmentally friendly, the derivatized products from these at the end of their lifetime could also be benign when designed appropriately. Bioethanol and biodiesel are examples of biobased industrial products currently in the market place and have become resources for uplifting the rural economy. Biolubricants also are playing a more prominent role because they have become closely competitive with petroleum-based lubricants. These products are renewable because the crops from which the feedstuff for the biofuels and biolubricants are produced are grown annually in contrast to nonrenewable mineral sources. Added to their renewability is the inherent biodegradability of their end-use products after their useful lifetime. In a recent study of the lubricity characteristics of peracylated polyhydroxy milkweed oil, the derivatives were found to exhibit good oxidative stability as well as excellent antiwear properties. To further explore an expansion in the properties of such materials in lubrication and other applications, in this study the polyhydroxy (OH) moieties of derivatized milkweed triglycerides were replaced with -NHR groupings in the oil. In this process novel polyketo triglyceride intermediates leading to polyamine derivatives of the vegetable oil have been synthesized. The polyamine triglyceride markedly improved the stability of the parent oil to oxidative stress. It has also attenuated the extreme viscosity of the starting polyhydroxy oil to a more useful product that could be amenable for use as a lubricating agent, for example, hydraulic fluid. Both the polyketone and polyimine intermediates of the polyamine have chelating properties. The intermediates and the polyamine were characterized spectroscopically

  11. Do polyamines contribute to plant cell wall assembly by forming amide bonds with pectins?

    Science.gov (United States)

    Lenucci, Marcello; Piro, Gabriella; Miller, Janice G; Dalessandro, Giuseppe; Fry, Stephen C

    2005-11-01

    Two new reducing glycoconjugates [N-D-galacturonoyl-putrescinamide (GalA-Put) and N,N'-di-D-galacturonoyl-putrescinamide (GalA-Put-GalA)] and homogalacturonan-putrescine (GalAn-Put) conjugates were synthesised as model compounds representing possible amide (isopeptide) linkage points between a polyamine and either one or two pectic galacturonate residues. The amide bond(s) were stable to cold acid and alkali (2M TFA and 0.1M NaOH at 25 degrees C) but rapidly hydrolysed by these agents at 100 degrees C. The amide bond(s) were resistant to Driselase and to all proteinases tested, although Driselase digested GalAn-Put, releasing fragments such as GalA3-Put-GalA3. To trace the possible formation of GalA-polyamine amide bonds in vivo, we fed Arabidopsis and rose cell-cultures and chickpea internodes with [14C]Put. About 20% of the 14C taken up was released as 14CO2, indicating some catabolism. An additional approximately 73% of the 14C taken up (in Arabidopsis), or approximately 21% (in rose), became ethanol-insoluble, superficially suggestive of polysaccharide-Put covalent bonding. However, much of the ethanol-inextractable 14C was subsequently extractable by acidified phenol or by cold 1M TFA. The small proportion of radioactive material that stayed insoluble in both phenol and TFA was hydrolysable by Driselase or hot 6M HCl, yielding 14C-oligopeptides and/or amino acids (including Asp, Glu, Gly, Ala and Val); no free 14C-polyamines were released by hot HCl. We conclude that if pectin-polyamine amide bonds are present, they are a very minor component of the cell walls of cultured rose and Arabidopsis cells and chickpea internodes.

  12. Targeting polyamine metabolism for finding new drugs against leishmaniasis: a review.

    Science.gov (United States)

    Ilari, Andrea; Fiorillo, Annarita; Baiocco, Paola; Poser, Elena; Angiulli, Gabriella; Colotti, Gianni

    2015-01-01

    Leishmaniasis is a neglected disease affecting more than 12 million people worldwide. The most used drugs are pentavalent antimonials that are very toxic and display the problem of drug resistance, especially in endemic regions such as Bihar in India. For this reason, it is urgent to find new and less toxic drugs against leishmaniasis. To this end, the understanding of pathways affecting parasite survival is of prime importance for targeted drug discovery. The parasite survival inside the macrophage is strongly dependent on polyamine metabolism. Polyamines are, in fact, very important for cell growth and proliferation. In particular, spermidine (Spd), the final product of the polyamine biosynthesis pathway, serves as a precursor for trypanothione (N1,N8- bis(glutathionyl)spermidine, T(SH)2) and hypusine (N(ε)-(4-amino-2-hydroxybutyl)lysine). T(SH)2 is a key molecule for parasite defense against the hydrogen peroxide produced by macrophages during the infection. Hypusination is a posttranslational modification occurring exclusively in the eukaryotic initiation factor 5A (eIF5A), which has an important role in avoiding the ribosome stalling during the biosynthesis of protein containing polyprolines sequences. The enzymes, belonging to the spermidine metabolism, i.e. arginase (ARG), ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC), spermidine synthase (SpdS), trypanothione synthetase (TryS or TSA), trypanothione reductase (TryR or TR), tryparedoxin peroxidase (TXNPx), deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are promising targets for the development of new drugs against leishmaniasis. This minireview furnishes a picture of the structural, functional and inhibition studies on polyamine metabolism enzymes that could guide the discovery of new drugs against leishmaniasis.

  13. Action orientation overcomes the ego depletion effect.

    Science.gov (United States)

    Dang, Junhua; Xiao, Shanshan; Shi, Yucai; Mao, Lihua

    2015-04-01

    It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task.

  14. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  15. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  16. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  17. Polyamines as new cationic plasticizers for pectin-based edible films.

    Science.gov (United States)

    Esposito, Marilena; Di Pierro, Prospero; Regalado-Gonzales, Carlos; Mariniello, Loredana; Giosafatto, C Valeria L; Porta, Raffaele

    2016-11-20

    Zeta potential and particle size were determined on pectin aqueous solutions as a function of pH and the effects of calcium ions, putrescine and spermidine on pectin film forming solutions and derived films were studied. Ca(2+) and polyamines were found to differently influence pectin zeta potential as well as thickness and mechanical and barrier properties of pectin films prepared at pH 7.5 either in the presence or absence of the plasticizer glycerol. In particular, Ca(2+) was found to increase film tensile strength and elongation at break only in the presence of glycerol and did not affect film thickness and permeability to both water vapor and CO2. Conversely, increasing polyamine concentrations progressively reduced film tensile strength and markedly enhanced film thickness, elongation at break and permeability to water vapor and CO2, both in the presence and absence of glycerol. Our findings indicate that polyamines give rise to a structural organization of the heteropolysaccharide different from that determined by calcium ions, previously described as "egg box" model, and suggest their possible application as plasticizers to produce pectin-based "bioplastics" with different features.

  18. Inhibition of polyamine oxidase activity affects tumor development during the maize-Ustilago maydis interaction.

    Science.gov (United States)

    Jasso-Robles, Francisco Ignacio; Jiménez-Bremont, Juan Francisco; Becerra-Flora, Alicia; Juárez-Montiel, Margarita; Gonzalez, María Elisa; Pieckenstain, Fernando Luis; García de la Cruz, Ramón Fernando; Rodríguez-Kessler, Margarita

    2016-05-01

    Ustilago maydis is a biotrophic plant pathogenic fungus that leads to tumor development in the aerial tissues of its host, Zea mays. These tumors are the result of cell hypertrophy and hyperplasia, and are accompanied by the reprograming of primary and secondary metabolism of infected plants. Up to now, little is known regarding key plant actors and their role in tumor development during the interaction with U. maydis. Polyamines are small aliphatic amines that regulate plant growth, development and stress responses. In a previous study, we found substantial increases of polyamine levels in tumors. In the present work, we describe the maize polyamine oxidase (PAO) gene family, its contribution to hydrogen peroxide (H2O2) production and its possible role in tumor development induced by U. maydis. Histochemical analysis revealed that chlorotic lesions and maize tumors induced by U. maydis accumulate H2O2 to significant levels. Maize plants inoculated with U. maydis and treated with the PAO inhibitor 1,8-diaminooctane exhibit a notable reduction of H2O2 accumulation in infected tissues and a significant drop in PAO activity. This treatment also reduced disease symptoms in infected plants. Finally, among six maize PAO genes only the ZmPAO1, which encodes an extracellular enzyme, is up-regulated in tumors. Our data suggest that H2O2 produced through PA catabolism by ZmPAO1 plays an important role in tumor development during the maize-U. maydis interaction.

  19. Nitric oxide, polyamines and Cd-induced phytotoxicity in wheat roots.

    Science.gov (United States)

    Groppa, M D; Rosales, E P; Iannone, M F; Benavides, M P

    2008-10-01

    To further explore the biochemical basis of Cd toxicity in developing wheat seedlings, we studied the possible role of nitric oxide (NO) and polyamines as signaling molecules involved in metal-induced root growth inhibition. When used at 0.1 mM, sodium nitroprusside, a NO-releasing compound, inhibited root growth to a similar extent as Cd and enhanced the polyamine contents as Cd also did. Putrescine and spermidine treatments caused significant decreases in root growth with spermine giving the greatest level of inhibition (77% reduction). The simultaneous addition of Cd and inhibitors of putrescine biosynthesis (DFMA and DFMO) prevented increases in putrescine levels but did not restore normal root growth. NO content, as evidenced by the fluorescent probe DAF-FM diacetate, was found to be significantly increased in the roots of both Cd and polyamine treated plants, especially in those exposed to spermine. The effect was specific for NO since the NO scavenger cPTIO almost suppressed the fluorescent signal. Concerning the oxidative status of the root system, only Cd and spermine enhanced lipid peroxidation in roots. At the same time, all treatments led to a significant increase in levels of the non-enzymatic antioxidant defense glutathione. Our results strongly suggest that Cd and spermine treatments induce NO formation in wheat roots which, in turn, is involved in root growth inhibition.

  20. A tumour suppressor network relying on the polyamine-hypusine axis.

    Science.gov (United States)

    Scuoppo, Claudio; Miething, Cornelius; Lindqvist, Lisa; Reyes, José; Ruse, Cristian; Appelmann, Iris; Yoon, Seungtai; Krasnitz, Alexander; Teruya-Feldstein, Julie; Pappin, Darryl; Pelletier, Jerry; Lowe, Scott W

    2012-07-12

    Tumour suppressor genes encode a broad class of molecules whose mutational attenuation contributes to malignant progression. In the canonical situation, the tumour suppressor is completely inactivated through a two-hit process involving a point mutation in one allele and chromosomal deletion of the other. Here, to identify tumour suppressor genes in lymphoma, we screen a short hairpin RNA library targeting genes deleted in human lymphomas. We functionally identify those genes whose suppression promotes tumorigenesis in a mouse lymphoma model. Of the nine tumour suppressors we identified, eight correspond to genes occurring in three physically linked 'clusters', suggesting that the common occurrence of large chromosomal deletions in human tumours reflects selective pressure to attenuate multiple genes. Among the new tumour suppressors are adenosylmethionine decarboxylase 1 (AMD1) and eukaryotic translation initiation factor 5A (eIF5A), two genes associated with hypusine, a unique amino acid produced as a product of polyamine metabolism through a highly conserved pathway. Through a secondary screen surveying the impact of all polyamine enzymes on tumorigenesis, we establish the polyamine-hypusine axis as a new tumour suppressor network regulating apoptosis. Unexpectedly, heterozygous deletions encompassing AMD1 and eIF5A often occur together in human lymphomas and co-suppression of both genes promotes lymphomagenesis in mice. Thus, some tumour suppressor functions can be disabled through a two-step process targeting different genes acting in the same pathway.

  1. Effect of polyamine analogues on hypusine content in JURKAT T-cells.

    Science.gov (United States)

    Bergeron, R J; Weimar, W R; Müller, R; Zimmerman, C O; McCosar, B H; Yao, H; Smith, R E

    1998-09-24

    The availability of synthetic hypusine and deoxyhypusine has made it possible to develop analytical methods which allow for the measurement of these compounds in various tissues. The methods involve dansylation of extracts from the pellet remaining after perchloric acid precipitation of cell or tissue homogenates, followed by high-performance liquid chromatography. To demonstrate the utility of this approach, the impact of four polyamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N14-diethylhomospermine (DEHSPM), 1,6,12-triazadodecane [(4,5) triamine], and 1,7, 13-triazatridecane [(5,5) triamine], on hypusine levels in a human T-cell line (JURKAT) is evaluated. All four analogues are active in controlling cell growth and compete well with spermidine for the polyamine transport apparatus. After 144 h of exposure to JURKAT cells, DENSPM reduces putrescine to below detectable limits and spermidine to 10% of the level in control cells. The other three analogues diminish both putrescine and spermidine to below detectable limits. The effectiveness with which the compounds lower spermine levels is DENSPM > DEHSPM > (4,5) triamine > (5,5) triamine. The analogues decrease the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in a similar fashion. Of the four polyamines, DENSPM and DEHSPM are potent at lowering intracellular hypusine levels after 144 h: 59 +/- 9% and 73 +/- 12% of control levels, respectively. The other two analogues have marginal effects.

  2. Fate of orally administered {sup 15}N-labeled polyamines in rats bearing solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masaki; Samejima, Keijiro; Goda, Hitomi; Niitsu, Masaru [Josai Univ., Sakado, Saitama (Japan). Faculty of Pharmaceutical Sciences; Xu Yongji [Qingdao Univ. of Science and Technology (China). Inst. of Chemical and Molecular Technology; Takahashi, Masakazu [Sasaki Inst., Tokyo (Japan); Hashimoto, Yoshiyuki [Kyoritsu Coll. of Pharmacy, Tokyo (Japan)

    2003-03-01

    We studied absorption, distribution, metabolism, and excretion of polyamines (putrescine, spermidine, and spermine) in the gastrointestinal tract using {sup 15}N-labeled polyamines as tracers and ionspray ionization mass spectrometry (IS-MS). The relatively simple protocol using rats bearing solid tumors provided useful information. Three {sup 15}N-labeled polyamines that were simultaneously administered were absorbed equally from gastrointestinal tract, and distributed within tissues at various concentrations. The uptake of {sup 15}N-spermidine seemed preferential to that of {sup 15}N-spermine since the concentrations of {sup 15}N-spermidine in the liver and tumors were higher, whereas those of {sup 15}N-spermine were higher in the kidney, probably due to the excretion of excess extracellular spermine. Most of the absorbed {sup 15}N-putrescine seemed to be lost, suggesting blood and tissue diamine oxidase degradation. Concentrations of {sup 15}N-spermidine and {sup 15}N-spermine in the tumor were low. We also describe the findings from two rats that were administered with {sup 15}N-spermine. The tissue concentrations of {sup 15}N-spermine were unusually high, and significant levels of {sup 15}N-spermidine were derived from {sup 15}N-spermine in these animals. (author)

  3. Advances in Polyamines of Insects%昆虫多胺的研究进展

    Institute of Scientific and Technical Information of China (English)

    王勋建; 王满囷

    2011-01-01

    多胺(腐胺、精胺、亚精胺)广泛存在于原核和真核细胞中,在细胞的生长和增殖过程中起着重要作用.介绍了昆虫体内多胺的种类、生物合成及与昆虫卵黄发生、胚胎发育、生长变态、行为、激素调节等相互作用的研究结果,并展望了其研究前景.%Polyamines (putrescine, spermidine and spermine) which are ubiquitous polycations in prokaryotic and eukaryotic cells play fundamental roles in cell growth and cell differentiation. The kinds and biosynthesis of polyamines in insects were introduced, the research advances in mutual relationships between polyamines and the vitellogenesis, embryonic development, metamorphosis, behavior, and hormones of insects were generdized. The expectation was described.

  4. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

    Science.gov (United States)

    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

  5. Behavior of Polyamine Fixing Agents on Agglomeration of Dissolved and Colloidal Substances in Papermaking

    Directory of Open Access Journals (Sweden)

    Yiqian Zhang

    2013-11-01

    Full Text Available Five polyamine fixing agents with different molecular weights but slightly different charge densities were used to treat a deinked pulp. Their efficacy in controlling colloidal substances (CS in the pulp was measured using focused beam reflectance measurements (FBRM. The objective was to determine if the colloidal substances were affected by the fixing agents by a “colloidal fixation” mechanism, i.e., colloidal particles being fixed onto pulp fiber in an un-agglomerated, single-particle state, or a “colloidal agglomeration” one, i.e., colloidal particles being coagulated by fixing agents into bigger agglomerates. The results showed that colloidal fixation does take place, especially for the polyamine with the smallest molecular weight. Among the five polyamines, it was found that higher molecular weights tended to result in more extensive colloidal agglomeration, but the effect of charge density was almost insignificant. Because it is efficient in differentiating between these two fixation mechanisms, FBRM is a powerful tool in screening different fixing agents.

  6. Physics of Fully Depleted CCDs

    CERN Document Server

    Holland, S E; Kolbe, W F; Lee, J S

    2014-01-01

    In this work we present simple, physics-based models for two effects that have been noted in the fully depleted CCDs that are presently used in the Dark Energy Survey Camera. The first effect is the observation that the point-spread function increases slightly with the signal level. This is explained by considering the effect on charge-carrier diffusion due to the reduction in the magnitude of the channel potential as collected signal charge acts to partially neutralize the fixed charge in the depleted channel. The resulting reduced voltage drop across the carrier drift region decreases the vertical electric field and increases the carrier transit time. The second effect is the observation of low-level, concentric ring patterns seen in uniformly illuminated images. This effect is shown to be most likely due to lateral deflection of charge during the transit of the photogenerated carriers to the potential wells as a result of lateral electric fields. The lateral fields are a result of space charge in the fully...

  7. Efficient removal of uranium from mice by a novel compound of fullerence multi-macrocyclic polyamine derivatives

    Institute of Scientific and Technical Information of China (English)

    刘晓青; 杨吉军; 唐军; 刘宁; 杨远友; 廖家莉; 欧巍; 孔芳; 兰静波; 罗顺忠; 刘国平; 何佳恒

    2015-01-01

    Uranium removal efficacy of fullerence multi-macrocyclic polyamine derivatives (C60-MMP), a novel chelat-ing agent, was evaluated in mice. C60-MMP was administrated intravenously into mice at 30 min after the uranium contamination. The molar ratio of chelating ligand/uranium was about 1:1. The results indicate that C60-MMP can effectively prevent accumulation of uranium in liver at 8 h after C60-MMP injection. At 48 h af-ter the last injection, uranium deposition in liver of C60-MMP treated mice is approximately 65%less than that of the control group. C60-MMP reacted positively in promoting the removal of uranium from kidney, and the urinary uranium excretion increased significantly, compared with the control and DTPA-treated mice. However, repeated administration of C60-MMP, and combined injection of DTPA and C60-MMP, did not show desirable effects on uranium removal from mice. It implies that more investigations are needed for the treatment protocols and clinical applications of C60-MMP.

  8. The 1988 Antarctic ozone depletion - Comparison with previous year depletions

    Science.gov (United States)

    Schoeberl, Mark R.; Stolarski, Richard S.; Krueger, Arlin J.

    1989-01-01

    The 1988 spring Antarctic ozone depletion was observed by TOMS to be substantially smaller than in recent years. The minimum polar total ozone values declined only 15 percent during September 1988, compared to nearly 50 percent during September 1987. At southern midlatitudes, exceptionally high total ozone values were recorded beginning in July 1988. The total integrated southern hemispheric ozone increased rapidly during the Austral spring, approaching 1980 levels during October. The high midlatitude total ozone values were associated with a substantial increase in eddy activity as indicated by the standard deviation in total ozone in the zonal band 30-60 deg S. Mechanisms through which the increased midlatitude eddy activity could disrupt the formation of the Antarctic ozone hole are briefly discussed.

  9. Growth status significantly affects the response of human lung cancer cells to antitumor polyamine-analogue exposure.

    Science.gov (United States)

    Carlisle, Diane L; Devereux, Wendy L; Hacker, Amy; Woster, Patrick M; Casero, Robert A

    2002-08-01

    Human solid tumors frequently have a relatively small growth fraction,which interferes with the action of many chemotherapeutic agents that target actively cycling cells. Several polyamine analogues are currently being developed for clinical application against human solid tumors including N1,N11-bis(ethyl)norspermine. Therefore, an effort was made to examine the effects of growth rate on polyamine-analogue efficacy. Low growth fraction (LGF) cell cultures of the human non-small cell lung cancer cell line NCI-H157 were generated to partially mimic solid tumors with low mitotic indices. Log-phase cells were compared with LGF cells with respect to cell survival and biochemical effects after exposure to polyamine analogues. The results demonstrate generally that LGF NCI-H157 cells were sensitive to analogue treatment. However, the dose necessary to elicit a response in LGF cells was an order of magnitude higher than the dose needed in log-phase cells. Additionally, the biochemical effects of analogues were similar between log phase and LGF cells with regard to a down-regulation of polyamine biosynthesis as measured by ornithine decarboxylase activity and an increase in polyamine catabolism as indicated by an increase in spermidine/spermine N1-acetyltransferase activity. However, biochemical effects were less dramatic in the LGF cells than those observed in the log-phase cells. The overall results of these studies suggest that the growth status of solid tumors can significantly affect the response to antitumor polyamine analogues, and growth fraction must be considered in the continued development and use of the polyamine analogues.

  10. Preparation of a new nanobiosensor for the determination of some biogenic polyamines and investigation of their interaction with DNA.

    Science.gov (United States)

    Bagheryan, Zahra; Noori, Abolhassan; Zahra Bathaie, S; Yousef-Elahi, Mozhdeh; Mousavi, Mir F

    2016-03-15

    Biogenic polyamines are small organic polycations involving in a variety of biological processes. They form high affinity complexes with DNA. Here, we have followed two different novel approaches, either fabrication of an electrochemical nanobiosensor for determination of three of the most important biogenic polyamines; spermine (SPM), spermidine (SPD) and putrescine (PUT), or electrochemical investigation of their interaction with DNA. Strong binding of polyamines to DNA makes the DNA a suitable recognition element for construction of a sensitive biosensor. The fabricated biosensor responded to SPM, SPD and PUT over an extended dynamic range of 0.04-100 μM, 0.01-24 μM, and 0.08-100 μM respectively, with low detection limits of a few nM. We also studied the interaction of polyamines with three different DNA sequences with base composition of 100% AT, 80% AT and 100% GC in the presence of [Ru(NH3)6]3(+) as a redox probe. The highest kb values were obtained in the interaction of polyamines with 80% AT (mixed) DNA sequence. The kb values were 5.24 × 10(5), 4.17 × 10(5) and 1.46 × 10(5)M(-1) for SPM, SPD and PUT, respectively, which correlated well with their increasing number of amino groups. In addition, competition study showed the impotence of SPD to replace with histone H1 in histone H1-DNA complex, which indicates the more potent interaction of histone H1 with DNA. In this proof-of-principle study, we have proposed an approach for simple, cost-effective, miniaturizable, and direct-readout detection of polyamines, as well as the understanding of the modes of interaction between polyamines and DNA.

  11. Effects of Polyamines Synthesis Inhibitors Sprayed after Heading on Contents and Components of Polyamines in Rice Grains at the Ripening Stage

    Institute of Scientific and Technical Information of China (English)

    JI Xiao-jia; YU Bing-jun; ZHANG Da-dong; LIU You-liang

    2005-01-01

    With a higher polyamine rice (indica variety Jinlingxiang) as experimental material, the changes in contents andcomponents of polyamines (PAs) in rice grains after harvesting were investigated under the treatments by spraying the panicles andflag leaves of rice with PAs synthesis inhibitors, D-Arg (0.5, 1.0, 1.5 and 2.0 mmol/L), methylglyoxal bis-guanylhydrazone (MGBG)(0.1, 0.5, 1.0 and 1.5 mmol/L) and cyclohexylamine (CHA) (1.0, 5.0, 10.0, 15.0 and 20.0 mmol/L), at the heading, flowering andgrain filling stages. The inhibition of D-Arg on the contents of free and bound PAs and its total amounts in rice grains was significant,especially treated at the flowering and grain filling stages. Treatments with MGBG and CHA affected mainly the components of PAs,and their effects on the total amounts of PAs were not significant except MGBG at the flowering stage and CHA at both heading andflowering stages.

  12. Gamma-Glutamylpolyamine Synthetase GlnA3 Is Involved in the First Step of Polyamine Degradation Pathway in Streptomyces coelicolor M145

    Directory of Open Access Journals (Sweden)

    Agnieszka Bera

    2017-04-01

    Full Text Available Streptomyces coelicolor M145 was shown to be able to grow in the presence of high concentrations of polyamines, such as putrescine, cadaverine, spermidine, or spermine, as a sole nitrogen source. However, hardly anything is known about polyamine utilization and its regulation in streptomycetes. In this study, we demonstrated that only one of the three proteins annotated as glutamine synthetase-like protein, GlnA3 (SCO6962, was involved in the catabolism of polyamines. Transcriptional analysis revealed that the expression of glnA3 was strongly induced by exogenous polyamines and repressed in the presence of ammonium. The ΔglnA3 mutant was shown to be unable to grow on defined Evans agar supplemented with putrescine, cadaverine, spermidine, and spermine as sole nitrogen source. HPLC analysis demonstrated that the ΔglnA3 mutant accumulated polyamines intracellularly, but was unable to degrade them. In a rich complex medium supplemented with a mixture of the four different polyamines, the ΔglnA3 mutant grew poorly showing abnormal mycelium morphology and decreased life span in comparison to the parental strain. These observations indicated that the accumulation of polyamines was toxic for the cell. An in silico analysis of the GlnA3 protein model suggested that it might act as a gamma-glutamylpolyamine synthetase catalyzing the first step of polyamine degradation. GlnA3-catalyzed glutamylation of putrescine was confirmed in an enzymatic in vitro assay and the GlnA3 reaction product, gamma-glutamylputrescine, was detected by HPLC/ESI-MS. In this work, the first step of polyamine utilization in S. coelicolor has been elucidated and the putative polyamine utilization pathway has been deduced based on the sequence similarity and transcriptional analysis of homologous genes expressed in the presence of polyamines.

  13. Increase in cell viability by polyamines through stimulation of the synthesis of ppGpp regulatory protein and ω protein of RNA polymerase in Escherichia coli.

    Science.gov (United States)

    Terui, Yusuke; Akiyama, Mariko; Sakamoto, Akihiko; Tomitori, Hideyuki; Yamamoto, Kaneyoshi; Ishihama, Akira; Igarashi, Kazuei; Kashiwagi, Keiko

    2012-02-01

    It is known that polyamines increase cell growth through stimulation of the synthesis of several kinds of proteins encoded by the so-called "polyamine modulon". We recently reported that polyamines also increase cell viability at the stationary phase of cell growth through stimulation of the synthesis of ribosome modulation factor, a component of the polyamine modulon. Accordingly, we looked for other proteins involved in cell viability whose synthesis is stimulated by polyamines. It was found that the synthesis of ppGpp regulatory protein (SpoT) and ω protein of RNA polymerase (RpoZ) was stimulated by polyamines at the level of translation. Stimulation of the synthesis of SpoT and RpoZ by polyamines was due to an inefficient initiation codon UUG in spoT mRNA and an unusual location of a Shine-Dalgarno (SD) sequence in rpoZ mRNA. Accordingly, the spoT and rpoZ genes are components of the polyamine modulon involved in cell viability. Reduced cell viability caused by polyamine deficiency was prevented by modified spoT and rpoZ genes whose synthesis was not influenced by polyamines. Under these conditions, the level of ppGpp increased in parallel with increase of SpoT protein. The results indicate that polyamine stimulation of synthesis of SpoT and RpoZ plays important roles for cell viability through stimulation of ppGpp synthesis by SpoT and modulation of RNA synthesis by ppGpp-RpoZ complex.

  14. Polyamines mediate abnormal Ca/sup 2 +/ transport and Ca/sup 2 +/-induced cardiac cell injury in the calcium paradox

    Energy Technology Data Exchange (ETDEWEB)

    Trout, J.J.; Koenig, H.; Goldstone, A.D.; Lu, C.Y.; Fan, C.C.

    1986-03-05

    Ca/sup 2 +/-free perfusion renders heart cells Ca/sup 2 +/-sensitive so that readmission of Ca/sup 2 +/ causes a sudden massive cellular injury attributed to abnormal entry of Ca/sup 2 +/ into cells (Ca paradox). Hormonal stimulation of Ca/sup 2 +/ fluxes was earlier shown to be mediated by polyamines (PA). 5 min perfusion of rat heart with Ca/sup 2 +/-free medium induce a prompt 40-50% decline in levels of the PA putrescine (PUT), spermidine and spermine and their rate-regulatory synthetic enzyme ornithine decarboxylase (ODC), and readmission of Ca/sup 2 +/-containing medium abruptly (< 30-60 sec) increased the levels of ODC and PA. The ODC inhibitor ..cap alpha..-difluoromethylornithine (DFMO, 5mM) blocked Ca/sup 2 +/ reperfusion-induced increases in ODC and PA and also prevented increased /sup 45/Ca/sup 2 +/ uptake and heart injury, manifested by loss of contractility, release of enzymes (CPK, LDH), myoglobin and protein, and E.M. lesions (contracture bands, mitochondrial changes). 1 mM PUT negated DFMO inhibition, repleted heart PA and restored Ca/sup 2 +/ reperfusion-induced /sup 45/Ca/sup 2 +/ influx and cell injury. These data indicate that the Ca/sup 2 +/-directed depletion-repletion cycle of ODC and PA triggers excessive transsarcolemmal Ca/sup 2 +/ transport leading to the calcium paradox.

  15. Temperature stress in accumulation of free proline of pigeonpea seedlings from seeds treated with polyamines

    Directory of Open Access Journals (Sweden)

    Jéssica da Silva

    2015-02-01

    Full Text Available It was studied the effects of seed treatment with polyamines of pigeonpea for proline content of seedling in order to verify that the application of these polyamines attenuates temperature stress on germination and early seedling growth, and see if exogenous putrescine and spermidine induce the accumulation of proline, this amino acid may be biochemical and physiological indicator in seedlings that are under suboptimal temperatures and supraoptmail. The seeds of pigeonpea cv. BRS Mandarin and cv. Caqui, treated with a solution of 0.5 mM of putrescine and spermidine, were subjected to suboptimal temperature (20ºC, 18ºC, 16ºC and 14ºC and supraoptimal (36ºC, 38ºC, 40ºC and 44ºC for 24 hours and 48 hours. After these periods, were subjected to 25°C until day 10, when the percentage of seed germination were observed, the proline content of vegetative parts and the dry mass of the seedlings. A completely randomized design in a factorial arrangement was used 3x4x2+3 (solutions with polyamines, temperature stress by cooling/heating, time of exposure to stress, plus additional factors em25ºC with 0.0 mM and 0.5mM of Put and Spd, with four replicates of 25 seeds. The results were submitted to analysis of variance and means were compared by Tukey test at 5% probability, separately for each cultivar. Both exogenous polyamines attenuate the effects of cooling and heating, contributing to the growth of germinated seeds. Also, putrescine and spermidine exogenous mitigated the adverse effects by inducing proline accumulation, which leads to osmotic adjustment temperatures, although this physiological response has not minimized the negative effects of temperature stress on seedling growth of pigeonpea. Proline can be considered biochemical and physiological indicator in seedlings of both cultivars of pigeonpea treated with polyamines under temperature stress.

  16. Depleted uranium disposal options evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hertzler, T.J.; Nishimoto, D.D.; Otis, M.D. [Science Applications International Corp., Idaho Falls, ID (United States). Waste Management Technology Div.

    1994-05-01

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ``waste,`` but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity.

  17. Effects of stress temperatures of germination on polyamine titers of soybean seeds

    Science.gov (United States)

    Pineda-Mejia, Renan

    High and low stress temperatures during seed germination and seedling development limit total germination and the rate of germination and growth. Changes in polyamine (PA) concentrations in seeds of different species have been associated with germination, growth and environmental stresses such as temperature, drought, oxygen, chilling injury and osmotic conditions. Two studies were conducted to determine the effect of stress temperatures during germination and seedling development on polyamine titers in soybean seeds. Three germination temperatures, 25, 30, and 36°C were used in the first study to evaluate their influence on changes in polyamine concentrations in soybean seeds germinated at 76 and 90 hours. The polyamines (PAs), cadaverine (Cad), putrescine (Put), spermidine (Spd), agmatine (Agm), and spermine (Spin) were quantified by HPLC using a cation exchange column and an electrochemical detector. Cad, Put, Agm, and Spd declined as the germination temperatures increased from 25 to 36°C. Conversely, Spin increased considerably with an increase in temperature. Total germination was reduced from 97.2 to 92.5% as germination temperatures increased from 25 to 36°C. Germination time did not affect Cad, Agm and Spm, and total germination, however, the interaction between temperature and germination time for Put and Spd concentrations was significant. In the second study, changes in PA concentrations, seedling growth, germination time (t50), fresh and dry weight, and moisture content were measured in the embryonic axis and cotyledons of soybean seeds germinated at 10 and 25°C through six stages of germination dry seed (DS), testa split (TS), radicle at 10 mm (Ra-10), root hairs visible (RHV), secondary root primordia (SRP), and complete seedling (CS). The concentrations of Cad and Put in the embryonic axis, were significantly higher in seeds germinated under low temperature than in seeds at 25°C (approximately 10 and 3 fold respectively). However, this

  18. Biochemical effects and growth inhibition in MCF-7 cells caused by novel sulphonamido oxa-polyamine derivatives.

    Science.gov (United States)

    Pavlov, V; Lin, P Kong Thoo; Rodilla, V

    2002-04-01

    The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 pM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase. Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 microM of either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.

  19. CHANGES OF POLYAMINE METABOLISM IN HL-60 CELLS DURING THE INDUCTION OF DIFFERENTIATION BY RETINOIC ACID AND DIMETHYLSULFOXIDE

    Institute of Scientific and Technical Information of China (English)

    缪金明; 潘瑞彭; 欧阳仁荣

    1992-01-01

    The polyamines putrescine, spermidine and spermine have been implicated in the regulation of cell proliferation and differentiation. In this study, the changes of intracellular polyamine contents and activity of ornithine decarboxylase, a rate-limiting enzyme in the polyamine synthetic pathway, were studied. The results showed that both retinoic acid (RA) and dimethylsulfoxide (DMSO) could elevate intracellular putrescine level by more than 2-fold over control value, then it declined gradually. In RA-treated cells, transient increase in spermidine and spermine levels was noted. In contrast, the spermidine and spermine levels in DMSO-treated cells declined to about 50% of the level of control cells at 96 h. The measurement of ornithine decarboxylase activity demonstrated that the increase of intracellular putrescine in RA and DMSO treated cells was due to the polyamine synthesis by inducing ornithine decarboxylase which reached 2 to 4-fold higher over basic level at 2 h, and above 6-fold at 16 h. These results suggest that the polyamine metabolism may be involved in RA and DMSO-induced granulocytic differentiation of HL-60 promyelocytic leukemia cells.

  20. No consistent effects of ozone exposure for one growth season on levels of polyamines in Picea abies

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, J.E.; Jensen, E. [Tromsoe Univ. (Norway). Dept. of Plant Physiology and Microbiology

    1998-07-01

    It is well known that ozone is detrimental to plants, due to its action as a strong oxidant. Polyamines have been suggested as protecting against oxidative stress, and have been reported as being induced by ozone in plants. However, there is a paucity of data on tree species exposed to ozone for an extended period under field-like conditions. In the present investigation, mature spruce clones were exposed to ozone (200 or 400 {mu}g m{sup -3} air) in open-top chambers for an entire growth season at two localities in Norway, and levels of the polyamines putrescine, spermidine and spermine were measured. No consistent effects of ozone fumigation were found on levels of any of the polyamines; not for two clones showing visible injury (yellow needles), and not for four apparently healthy clones. Thus, there was no correlation between sensitivity or tolerance to ozone and polyamine content. However, there were significant differences in polyamine contents between clones and the two localities of exposure 18 refs, 3 figs

  1. Epithelial-mesenchymal interactions and lung branching morphogenesis. Role of polyamines and transforming growth factor ß1

    Directory of Open Access Journals (Sweden)

    G Stabellini

    2009-12-01

    Full Text Available Lung branching morphogenesis is a result of epithelial-mesenchymal interactions, which are in turn dependent on extracellular matrix composition and cytokine regulation. Polyamines have recently been demonstrated as able to modify chick embryo skin differentiation. In this work we have examined the effects of putrescine and spermidine during chick embryo lung morphogenesis in organotypic cultures by morphological, histochemical and biochemical examination. To verify the role of polyamines, we used specific inhibitors, such as bis-cyclohexylammonium sulphate and alfa-difluoromethylornithine, and transforming growth factor ß1, an ornithine decarboxylase and polyamine stimulator. Our data show that lung morphogenesis is significantly altered following the induced mesenchymal glycosaminoglycan changes. The increase of mesenchymal glycosaminoglycans is correlated with a stimulation of lung development in the presence of polyamines, and with its inhibition when transforming growth factor ß1 is added to the culture medium. The morphometric data show a uniform increase of both the mesenchyme and epithelial branching with spermidine and putrescine stimulus, whereas the mesenchymal substance alone is significantly increased in apical-median lung sections with transforming growth factor ß1 and transforming growth factor ß1 + spermidine lung cultures. Transforming growth factor ß1 and transforming growth factor ß1 + spermidine confirm the blocking of epithelial branching formations and fibroblast activation, and show that polyamines are unable to prevent the blocking of epithelial cells due to the inhibitory effect of transforming growth factor ß1.

  2. Effect of processing on polyamine content and bioactive peptides released after in vitro gastrointestinal digestion of infant formulas.

    Science.gov (United States)

    Gómez-Gallego, C; Recio, I; Gómez-Gómez, V; Ortuño, I; Bernal, M J; Ros, G; Periago, M J

    2016-02-01

    This study examined the influence of processing on polyamines and peptide release after the digestion of a commercial infant formula designed for children during the first months of life. Polyamine oxidase activity was not suppressed during the manufacturing process, which implicates that polyamine concentrations were reduced over time and during infant formula self-life. In gel electrophoresis, in vitro gastrointestinal digestion of samples with reduced amount of enzymes and time of digestion shows an increase in protein digestibility, reflected in the increase in nonprotein nitrogen after digestion and the disappearance of β-lactoglobulin and α-lactalbumin bands in gel electrophoresis. Depending on the sample, between 22 and 87 peptides were identified after gastrointestinal digestion. A peptide from β-casein f(98-105) with the sequence VKEAMAPK and antioxidant activity appeared in all of the samples. Other peptides with antioxidant, immunomodulatory, and antimicrobial activities were frequently found, which could have an effect on infant health. The present study confirms that the infant formula manufacturing process determines the polyamine content and peptidic profile after digestion of the infant formula. Because compositional dissimilarity between human milk and infant formula in polyamines and proteins could be responsible for some of the differences in health reported between breast-fed and formula-fed children, these changes must be taken into consideration because they may have a great effect on infant nutrition and development.

  3. Altered expression of polyamine transporters reveals a role for spermidine in the timing of flowering and other developmental response pathways.

    Science.gov (United States)

    Ahmed, Sheaza; Ariyaratne, Menaka; Patel, Jigar; Howard, Alexander E; Kalinoski, Andrea; Phuntumart, Vipaporn; Morris, Paul F

    2017-05-01

    Changes in the levels of polyamines are correlated with the activation or repression of developmental response pathways, but the role of polyamine transporters in the regulation of polyamine homeostasis and thus indirectly gene expression, has not been previously addressed. Here we show that the A. thaliana and rice transporters AtPUT5 and OsPUT1 were localized to the ER, while the AtPUT2, AtPUT3, and OsPUT3 were localized to the chloroplast by transient expression in N. benthamiana. A. thaliana plants that were transformed with OsPUT1 under the control the PUT5 promoter were delayed in flowering by 16days. In contrast, put5 mutants flowered four days earlier than WT plants. The delay of flowering was associated with significantly higher levels of spermidine and spermidine conjugates in the leaves prior to flowering. A similar delay in flowering was also noted in transgenic lines with constitutive expression of either OsPUT1 or OsPUT3. All three transgenic lines had larger rosette leaves, thicker flowering stems, and produced more siliques than wild type plants. In contrast, put5 plants had smaller leaves, thinner flowering stems, and produced fewer siliques. Constitutive expression of PUTs was also associated with an extreme delay in both plant senescence and maturation rate of siliques. These experiments provide the first genetic evidence of polyamine transport in the timing of flowering, and indicate the importance of polyamine transporters in the regulation of flowering and senescence pathways.

  4. The inhibition of PI3K and NFκB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells.

    Science.gov (United States)

    Berrak, Özge; Akkoç, Yunus; Arısan, Elif Damla; Çoker-Gürkan, Ajda; Obakan-Yerlikaya, Pınar; Palavan-Ünsal, Narçin

    2016-02-01

    Bcl-2 protein has been contributed with number of genes which are involved in oncogenesis. Among the many targets of Bcl-2, NFκB have potential role in induction of cell cycle arrest. Curcumin has potential therapeutic effects against breast cancer through multiple signaling pathways. In this study, we investigated the role of curcumin in induction of cell cycle arrest via regulating of NFκB and polyamine biosynthesis in wt and Bcl-2+ MCF-7 cells. To examine the effect of curcumin on cell cycle regulatory proteins, PI3K/Akt, NFκB pathways and polyamine catabolism, we performed immunoblotting assay. In addition, cell cycle analysis was performed by flow cytometry. The results indicated that curcumin induced cell cycle arrest at G2/M phase by downregulation of cyclin B1 and Cdc2 and inhibited colony formation in MCF-7wt cells. However, Bcl-2 overexpression prevented the inhibition of cell cycle associated proteins after curcumin treatment. The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. Moreover, LY294002 further inhibited the phosphorylation of Akt in Bcl-2+ MCF-7 cells. Curcumin could suppress the nuclear transport of NFκB through decreasing the interaction of P-IκB-NFκB. The combination of wedelolactone, NFκB inhibitor, and curcumin acted different on SSAT expression in wt MCF-7 and Bcl-2+ MCF-7 cells. NFκB inhibition increased the SSAT after curcumin treatment in Bcl-2 overexpressed MCF-7 cells. Inhibition of NFκB activity as well as suppression of ROS generation with NAC resulted in the partial relief of cells from G2/M checkpoint after curcumin treatment in wt MCF-7 cells. In conclusion, the potential role of curcumin in induction of cell cycle arrest is related with NFκB-regulated polyamine biosynthesis.

  5. INFLUENCE ON THE STRUCTURE AND FUNCTION OF RAT HEART UNDER THE CONDITION OF BLOOD LOSS COMBINED WITH HYPOXIA, WATER AND DIETARY DEPLETION%失血复合缺氧缺水缺食对大鼠心脏功能和心肌结构的影响

    Institute of Scientific and Technical Information of China (English)

    于瑜; 左红艳; 王德文; 王少霞; 彭瑞云; 闫傲霜

    2011-01-01

    hypoxia( 10% of oxygen) combined with water and dietary depletion. Blood biochemical,common pathological, idtramicro-pathological, and quantitative pathological methods were used to detect the changes of cardiac structure and function after 1d, 3d, 5d, 7dof exposure respectively. Results The level of CK and LDH both decreased in the group of blood loss, but AST had no obvious changes. The levels of AST, LDH and CK became lower and then higher under the condition of hypoxia combined with water and dietary depletion. The changes of cardiac enzymes became serious combined again with blood loss. The chief pathological changes of heart in hypoxia, combined with water and dietary depletion group ,and blood loss alone group were myocardial cell degeneration, apoptosis and necrosis. Cardiomyofilaments were disarranged,broken, even deliquescent; mitochondria were swollen; and vascular endothelial cells showed apoptosis. The above changes were in aggravation during 1 - 7 d of exposure. Cardiac structural injury became serious combined with blood loss. Conclusion Structural and functional injury of rat heart occurred under the condition of hypoxia combined with water and dietary depletion. Furthermore, the injury was in aggravation with exposure time continuing and combined with blood loss in addition.

  6. An equilibrium model for ligand-modified micellar-enhanced ultrafiltration. Selective separation of metal ions using iminoacetic substituted polyamines and a theoretical model for the titration behavior of polyamines

    Energy Technology Data Exchange (ETDEWEB)

    Dharmawardana, Udeni Rajaratna [Univ. of Oklahoma, Norman, OK (United States)

    1992-01-01

    This thesis consists of three chapters. Chapter 1, An equilibrium model for ligand-modified micellar-enhanced ultrafiltration, describes a theoretical model and experimental investigations which used the semi-equilibrium-dialysis method with N-n-dodecyl iminodiacetic acid as the ligand. In Chapter 2, Selective separation of metal ions using iminoacetic substituted polyamines, polyamines with a substituted ligand group are synthesized and used in investigating selective separation of copper ions from aqueous solution. In Chapter 3, A theoretical model for the titration behavior of polyamines, a novel approach to explain the titration behavior of polymeric amines based on the binding behavior of counterions is described. The application of this study is to the investigation of inexpensive and efficient methods of industrial waste water treatment.

  7. Ego depletion increases risk-taking.

    Science.gov (United States)

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

    2012-01-01

    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings.

  8. A simple assay for mammalian spermine oxidase: a polyamine catabolic enzyme implicated in drug response and disease.

    Science.gov (United States)

    Goodwin, Andrew C; Murray-Stewart, Tracy R; Casero, Robert A

    2011-01-01

    Spermine oxidase (SMO), the most recently characterized polyamine metabolic enzyme, catalyzes the direct back-conversion of spermine to spermidine in an FAD-dependent reaction that also yields the byproducts hydrogen peroxide (H(2)O(2)) and 3-aminopropanal. These metabolites, particularly H(2)O(2), have been implicated in cytotoxic cellular responses to specific antitumor polyamine analogs, as well as in the inflammation-associated generation of DNA damage. This chapter describes a rapid, sensitive, and inexpensive method for the chemiluminescent measurement of SMO (or alternatively, N (1)-acetyl polyamine oxidase, APAO) enzyme activity in cultured cell lysates, without the need for radioactive reagents or the use of high performance liquid chromatography (HPLC). Specifically, H(2)O(2) production by SMO is coupled to chemiluminescence generated by the horseradish peroxidase-catalyzed oxidation of luminol. Detailed protocols for preparation of reagents, harvesting cell lysates, generation of a standard curve, assaying of samples, and calculation of SMO enzyme activity are presented.

  9. [Characteristics of polyamine biosynthesis regulation and tumor growth rate in hormone-dependant grafted breast tumors of mice and rats].

    Science.gov (United States)

    Orlovskiĭ, A A

    2007-01-01

    Effect of the inhibitors of polyamines biosynthesis on completely or partially hormone-dependant breast tumors (mouse Ca755 carcinoma and Walker W-256 carcinosarcoma) is essentially special: in contrary to hormone-dependant tumors, this effect may be not only breaking but stimulating as well. Change-over from one to another mode of reaction is conditioned, most probable, by hormonal status, which is determined by one or another estral cycle phase. Biochemical mechanisms of this change-over are closely connected with polyamines metabolism, namely the degree of polyamines (especially spermine) interconvertion and physiological reactivity level of the system controlling expression of ornithin-decarboxilase. At that, the first of these pathways is predominant for completely hormone-dependant Ca755 and the second one -for partially hormone-dependant W-256.

  10. Suppression of TNF-alpha production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines

    DEFF Research Database (Denmark)

    Yu, J.; Parlesak, Alexandr; Sauter, S.

    2006-01-01

    precursors or metabolites [phosphatidylcholine, choline, betaine, S-adenosylmethionine (SAM)] have a modulating effect on tumor necrosis factor alpha (TNF-alpha) production by endotoxin-stimulated human mononuclear leukocytes and whether SAM-dependent polyamines (spermidine, spermine) are mediators of SAM......-induced inhibition of TNF-alpha synthesis. Methionine and betaine had a moderate stimulatory effect on TNF-alpha production, whereas phosphatidylcholine (ID(50) 5.4 mM), SAM (ID(50) 131 microM), spermidine (ID(50) 4.5 microM) and spermine (ID(50) 3.9 microM) had a predominantly inhibitory effect. Putrescine did...... not alter TNF-alpha release. Inhibitors of polyamine synthesis that blocked either putrescine (difluoromethylornithine) or spermine (CGP48664A) production did not affect TNF-alpha synthesis. Endotoxin stimulation of leukocytes did not alter the intracellular levels of polyamines. In addition...

  11. The proapoptotic effect of combination PI3K p85α depletion and 5-FU treatment on colorectal cancer cells%PI3K p85α蛋白表达缺失联合5-FU对大肠癌细胞的促凋亡作用

    Institute of Scientific and Technical Information of China (English)

    孙嫣; 王林; 曾晖

    2011-01-01

    Objective To investigate the proapoptotic effect of combination PI3K p85α depletion via RNA interference and 5-FU treatment on colorectal cancer cells. Methods PI3K p85α/RNAi-LoVo cells and LoVo control cells were recovered and cultured in RPMII640, supplemented with 10% fetal calf serum and 500 μg/mL G418. Western blot analysis was used to determine the RNA interference effect. The 50% inhibitory concentration (IC50) value of 5-FU was evaluated by MTT assay. Annexin V-FITC Kit was used to determine the apoptosis. Results Western blot analysis showed that the inhibited rate of PI3K p85α protein was 59%. Compared with the control cells, IC50 of 5-FU in PI3K p85α/RNAi-LoVo cells obviously decreased (P = 0. 000). Depletion of PI3K p85α sensitized LoVo cells to 5-FU induced apoptosis (P =0. 000). Conclusion Combination PI3K p85α depletion and 5-FU treatment could promote apoptosis of LoVo cells. It may be a new therapeutic strategy for gene therapy and chemotherapy of colorectal cancer.%探讨RNA干扰靶向抑制PI3K p85α蛋白表达联合5-FU对大肠癌LoVo细胞的促凋亡作用.方法 复苏培养PI3K p85α干扰组LoVo细胞(PI3Kp85ɑ/RNAi-LoVo)和LoVo对照组细胞,Western blot鉴定干扰效果,MTT法检测5-FU对两组细胞的半数抑制浓度(IC50),Annexin-FITC标记法检测细胞凋亡.结果 Western blot结果显示LoVo干扰组细胞PI3K p85α蛋白抑制率为59%,MTT结果显示干扰组细胞5-FU的IC50值(4.57±0.16)μmol/L明显低于对照组细胞5-FU的IC50值(8.07±0.30)μmol/L (P=0.000),细胞凋亡实验显示,干扰组细胞对5-FU诱导凋亡的敏感性增加(P=0.000).结论 PI3K p85α蛋白表达缺失联合5-FU可促进大肠癌LoVo细胞凋亡,为基因治疗和化学药物联合治疗大肠癌提供新的策略.

  12. Depleted argon from underground sources

    Energy Technology Data Exchange (ETDEWEB)

    Back, H.O.; /Princeton U.; Alton, A.; /Augustana U. Coll.; Calaprice, F.; Galbiati, C.; Goretti, A.; /Princeton U.; Kendziora, C.; /Fermilab; Loer, B.; /Princeton U.; Montanari, D.; /Fermilab; Mosteiro, P.; /Princeton U.; Pordes, S.; /Fermilab

    2011-09-01

    Argon is a powerful scintillator and an excellent medium for detection of ionization. Its high discrimination power against minimum ionization tracks, in favor of selection of nuclear recoils, makes it an attractive medium for direct detection of WIMP dark matter. However, cosmogenic {sup 39}Ar contamination in atmospheric argon limits the size of liquid argon dark matter detectors due to pile-up. The cosmic ray shielding by the earth means that Argon from deep underground is depleted in {sup 39}Ar. In Cortez Colorado a CO{sub 2} well has been discovered to contain approximately 500ppm of argon as a contamination in the CO{sub 2}. In order to produce argon for dark matter detectors we first concentrate the argon locally to 3-5% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation. The N{sub 2} and He will be removed by continuous cryogenic distillation in the Cryogenic Distillation Column recently built at Fermilab. In this talk we will discuss the entire extraction and purification process; with emphasis on the recent commissioning and initial performance of the cryogenic distillation column purification.

  13. Depleted uranium hexafluoride: The source material for advanced shielding systems

    Energy Technology Data Exchange (ETDEWEB)

    Quapp, W.J.; Lessing, P.A. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Cooley, C.R. [Department of Technology, Germantown, MD (United States)

    1997-02-01

    The U.S. Department of Energy (DOE) has a management challenge and financial liability problem in the form of 50,000 cylinders containing 555,000 metric tons of depleted uranium hexafluoride (UF{sub 6}) that are stored at the gaseous diffusion plants. DOE is evaluating several options for the disposition of this UF{sub 6}, including continued storage, disposal, and recycle into a product. Based on studies conducted to date, the most feasible recycle option for the depleted uranium is shielding in low-level waste, spent nuclear fuel, or vitrified high-level waste containers. Estimates for the cost of disposal, using existing technologies, range between $3.8 and $11.3 billion depending on factors such as the disposal site and the applicability of the Resource Conservation and Recovery Act (RCRA). Advanced technologies can reduce these costs, but UF{sub 6} disposal still represents large future costs. This paper describes an application for depleted uranium in which depleted uranium hexafluoride is converted into an oxide and then into a heavy aggregate. The heavy uranium aggregate is combined with conventional concrete materials to form an ultra high density concrete, DUCRETE, weighing more than 400 lb/ft{sup 3}. DUCRETE can be used as shielding in spent nuclear fuel/high-level waste casks at a cost comparable to the lower of the disposal cost estimates. Consequently, the case can be made that DUCRETE shielded casks are an alternative to disposal. In this case, a beneficial long term solution is attained for much less than the combined cost of independently providing shielded casks and disposing of the depleted uranium. Furthermore, if disposal is avoided, the political problems associated with selection of a disposal location are also avoided. Other studies have also shown cost benefits for low level waste shielded disposal containers.

  14. Age dependency of the metabolic conversion of polyamines into amino acids in IMR-90 human embryonic lung diploid fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Chen, K.Y.; Chang, Z.

    1986-07-01

    When radioactive polyamines (putrescine or spermidine) were incubated with mammalian cells in tissue culture, the radioactivity was incorporated into cellular proteins via two different metabolic pathways; one is metabolic labeling of an 18,000-dalton protein via hypusine formation, and the other is general protein synthesis employing radioactive amino acids derived from biodegradation of polyamines via GABA shunt and Krebs cycle. Aminoguanidine, a potent inhibitor of diamine oxidase, blocked the metabolic conversion of polyamines to amino acids but had no effect on the metabolic labeling of the 18,000-dalton protein. The authors have investigated these two polyamine-associated biochemical events in IMR-90 human diploid fibroblasts as a function of their population doubling level (PDL). They found that (1) the metabolic labeling of the 18,000-dalton protein was about two-fold greater in young cells (PDL = 22) than that in old cells (PDL = 48), and (2) the metabolic labeling of other cellular proteins, employing amino acids derived from putrescine via polyamine catabolic pathway, was more than six-fold greater in the old cells (PDL = 48) than in the young cells (PDL = 22). Since the rate of protein synthesis was about 1.4-fold higher in the young cells as compared to the old cells, their data indicated that the activity of catabolic conversion of putrescine (or spermidine) to amino acids in old IMR-90 cells was about eight-fold greater than that in young cells. This remarkable increase of polyamine catabolism and the slight decrease of metabolic labeling of the 18,000-dalton protein were also observed in cell strains derived from patients with premature aging disease.

  15. Spermine oxidase is a regulator of macrophage host response to Helicobacter pylori: enhancement of antimicrobial nitric oxide generation by depletion of spermine.

    Science.gov (United States)

    Chaturvedi, Rupesh; Asim, Mohammad; Barry, Daniel P; Frye, Jeanetta W; Casero, Robert A; Wilson, Keith T

    2014-03-01

    The gastric pathogen Helicobacter pylori causes peptic ulcer disease and gastric cancer. We have reported that in H. pylori-activated macrophages, nitric oxide (NO) derived from inducible NO synthase (iNOS) can kill the bacterium, iNOS protein expression is dependent on uptake of its substrate L-arginine (L-Arg), the polyamine spermine can inhibit iNOS translation by inhibiting L-Arg uptake, and inhibition of polyamine synthesis enhances NO-mediated bacterial killing. Because spermine oxidase (SMO), which back-converts spermine to spermidine, is induced in macrophages by H. pylori, we determined its role in iNOS-dependent host defense. SMO shRNA knockdown in RAW 264.7 murine macrophages resulted in a marked decrease in H. pylori-stimulated iNOS protein, but not mRNA expression, and a 90% reduction in NO levels; NO production was also inhibited in primary murine peritoneal macrophages with SMO knockdown. There was an increase in spermine levels after H. pylori stimulation that rapidly decreased, while SMO knockdown caused a greater increase in spermine that was sustained. With SMO knockdown, L-Arg uptake and killing of H. pylori by macrophages was prevented. The overexpression of SMO by transfection of an expression plasmid prevented the H. pylori-stimulated increase in spermine levels, and led to increased L-Arg uptake, iNOS protein expression and NO production, and H. pylori killing. In two human monocytic cell lines, U937 and THP-1, overexpression of SMO caused a significant enhancement of NO production with H. pylori stimulation. By depleting spermine, SMO can abrogate the inhibitory effect of polyamines on innate immune responses to H. pylori by enhancing antimicrobial NO production.

  16. Change in plant cycle chemistry from hydrazine/phosphate to amine/polyamine treatment in an industrial power station

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, T.; Besl, G. [TUeV SUeD Industrie Service GmbH, Muenchen (Germany); Stecklina, M. [MD Papier GmbH, Dachau (Germany)

    2007-08-15

    In an industrial power station with several natural circulation boilers (permissible operation pressure 13.6 MPa), raw water treatment via demineralization, condensate polishing and thermal feedwater degasification, the cycle chemistry was changed from hydrazine/phosphate to amine/polyamine treatment. The modification was supervised by TUeV SUeD with several water chemical analyses of the water/steam circuit. No problematic water conditions were found during the investigations. Fewer condensate impurities and a reduced amount of boiler blowdown can be stated as positive results of the transition to the polyamine treatment. (orig.)

  17. High-performance liquid chromatographic determination of free and total polyamines in human serum as fluorescamine derivatives.

    Science.gov (United States)

    Kai, M; Ogata, T; Haraguchi, K; Ohkura, Y

    1979-06-11

    A highly sensitive and simple fluorimetric method for the determination of free and total polyamines, spermidine, spermine, putrescine and cadaverine, in human serum by high-performance liquid chromatography is described. The polyamines, obtained after clean-up of deproteinized serum by Cellex P column chromatography, are converted to their fluorescamine derivatives in the presence of nickel ion which inhibits the reaction of interfering amines with fluorescamine, and the derivatives are separated simultaneously by reversed-phase chromatography (LiChrosorb RP-18) with a linear gradient elution. The lower limits of detection are 10 and 15 pmole for spermine and the others in 0.5 ml of serum, respectively.

  18. Towards squalamine mimics: synthesis and antibacterial activities of head-to-tail dimeric sterol-polyamine conjugates.

    Science.gov (United States)

    Chen, Wen-Hua; Wennersten, Christine; Moellering, Robert C; Regen, Steven L

    2013-03-01

    Four dimeric sterol-polyamine conjugates have been synthesized from the homo- and hetero-connection of monomeric sterol-polyamine analogs in a head-to-tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria, whereas their corresponding activities against Gram-negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid-containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid-derived analogs. This is in contrast to the finding that a monomeric deoxycholic acid-spermine conjugate was more active than the corresponding cholic acid-derived analog.

  19. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Directory of Open Access Journals (Sweden)

    Feiler Heidi S

    2009-12-01

    Full Text Available Abstract Background Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. Methods A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. Results The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. Conclusions A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition. See the related commentary by Benes and Settleman: http://www.biomedcentral.com/1741-7015/7/78

  20. Spermine inhibits Vibrio cholerae biofilm formation through the NspS-MbaA polyamine signaling system.

    Science.gov (United States)

    Sobe, Richard C; Bond, Whitney G; Wotanis, Caitlin K; Zayner, Josiah P; Burriss, Marybeth A; Fernandez, Nicolas; Bruger, Eric L; Waters, Christopher M; Neufeld, Howard S; Karatan, Ece

    2017-08-21

    The aquatic bacterium and human intestinal pathogen, Vibrio cholerae, senses and responds to a variety of environment-specific cues to regulate biofilm formation. Specifically, the polyamines norspermidine and spermidine enhance and repress V. cholerae biofilm formation, respectively. These effects are relevant for understanding V. cholerae pathogenicity and are mediated through the periplasmic binding protein, NspS, and the transmembrane c-di-GMP phosphodiesterase MbaA. However, the levels of spermidine required to inhibit biofilm formation through this pathway are unlikely to be encountered by V. cholerae in aquatic reservoirs or within the human host during infection. We therefore hypothesized that other polyamines in the gastrointestinal tract may control V. cholerae biofilm formation at physiological levels. The tetramine spermine has been reported to be present at nearly 50 micromolar concentrations in the intestinal lumen. Here, we report that spermine acts as an exogenous cue that inhibits V. cholerae biofilm formation through the NspS-MbaA signaling system. We found that this effect likely occurs through a direct interaction of spermine with NspS, as purified NspS protein could bind spermine in vitro Spermine also inhibited biofilm formation by altering the transcription of the vps genes involved in biofilm matrix production. Global c-di-GMP levels were unaffected by spermine supplementation, suggesting that biofilm formation may be regulated by variations in local rather than global c-di-GMP pools. Finally, we propose a model illustrating how the NspS-MbaA signaling system may communicate exogenous polyamine content to the cell to control biofilm formation in the aquatic environment and within the human intestine. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  1. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Wen-Lin; Das, Debopriya; Ziyad, Safiyyah; Bhattacharya, Sanchita; Gibb, William J.; Heiser, Laura M.; Sadanandam, Anguraj; Fontenay, Gerald V.; Hu, Zhi; Wang, Nicholas J.; Bayani, Nora; Feiler, Heidi S.; Neve, Richard M.; Wyrobek, Andrew J.; Spellman, Paul T.; Marton, Laurence J.; Gray, Joe W.

    2009-11-14

    Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signaling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.

  2. Role of a Hydrophobic Pocket in Polyamine Interactions with the Polyspecific Organic Cation Transporter OCT3.

    Science.gov (United States)

    Li, Dan C; Nichols, Colin G; Sala-Rabanal, Monica

    2015-11-13

    Organic cation transporter 3 (OCT3, SLC22A3) is a polyspecific, facilitative transporter expressed in astrocytes and in placental, intestinal, and blood-brain barrier epithelia, and thus elucidating the molecular mechanisms underlying OCT3 substrate recognition is critical for the rational design of drugs targeting these tissues. The pharmacology of OCT3 is distinct from that of other OCTs, and here we investigated the role of a hydrophobic cavity tucked within the translocation pathway in OCT3 transport properties. Replacement of an absolutely conserved Asp by charge reversal (D478E), neutralization (D478N), or even exchange (D478E) abolished MPP(+) uptake, demonstrating this residue to be obligatory for OCT3-mediated transport. Mutations at non-conserved residues lining the putative binding pocket of OCT3 to the corresponding residue in OCT1 (L166F, F450L, and E451Q) reduced the rate of MPP(+) transport, but recapitulated the higher sensitivity pharmacological profile of OCT1. Thus, interactions of natural polyamines (putrescine, spermidine, spermine) and polyamine-like potent OCT1 blockers (1,10-diaminodecane, decamethonium, bistriethylaminodecane, and 1,10-bisquinuclidinedecane) with wild-type OCT3 were weak, but were significantly potentiated in the mutant OCT3s. Conversely, a reciprocal mutation in OCT1 (F161L) shifted the polyamine-sensitivity phenotype toward that of OCT3. Further analysis indicated that OCT1 and OCT3 can recognize essentially the same substrates, but the strength of substrate-transporter interactions is weaker in OCT3, as informed by the distinct makeup of the hydrophobic cleft. The residues identified here are key contributors to both the observed differences between OCT3 and OCT1 and to the mechanisms of substrate recognition by OCTs in general.

  3. Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis.

    Science.gov (United States)

    Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki; Dever, Thomas E

    2017-08-21

    Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  4. Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

    Science.gov (United States)

    Russo, Francesco; Linsalata, Michele; Orlando, Antonella

    2014-10-07

    Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

  5. Role of plastid transglutaminase in LHCII polyamination and thylakoid electron and proton flow.

    Directory of Open Access Journals (Sweden)

    Nikolaos E Ioannidis

    Full Text Available Transglutaminases function as biological glues in animal cells, plant cells and microbes. In energy producing organelles such as chloroplasts the presence of transglutaminases was recently confirmed. Furthermore, a plastidial transglutaminase has been cloned from maize and the first plants overexpressing tgz are available (Nicotiana tabacum TGZ OE. Our hypothesis is that the overexpression of plastidal transglutaminase will alter photosynthesis via increased polyamination of the antenna of photosystem II. We have used standard analytical tools to separate the antenna from photosystem II in wild type and modified plants, 6 specific antibodies against LHCbs to confirm their presence and sensitive HPLC method to quantify the polyamination level of these proteins. We report that bound spermidine and spermine were significantly increased (∼80% in overexpressors. Moreover, we used recent advances in in vivo probing to study simultaneously the proton and electron circuit of thylakoids. Under physiological conditions overexpressors show a 3-fold higher sensitivity of the antenna down regulation loop (qE to the elicitor (luminal protons which is estimated as the ΔpH component of thylakoidal proton motive force. In addition, photosystem (hyper-PSIIα with an exceptionally high antenna (large absorption cross section, accumulate in transglutaminase over expressers doubling the rate constant of light energy utilization (Kα and promoting thylakoid membrane stacking. Polyamination of antenna proteins is a previously unrecognized mechanism for the modulation of the size (antenna absorption cross section and sensitivity of photosystem II to down regulation. Future research will reveal which peptides and which residues of the antenna are responsible for such effects.

  6. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; Vet, De Emely; Ridder, De Denise T.D.

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  7. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.|info:eu-repo/dai/nl/304823023; Fennis, Bob M.; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  8. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  9. Identifying water mass depletion in Northern Iraq observed by GRACE

    Directory of Open Access Journals (Sweden)

    G. Mulder

    2014-10-01

    Full Text Available Observations acquired by Gravity Recovery And Climate Experiment (GRACE mission indicate a mass loss of 31 ± 3 km3 or 130 ± 14 mm in Northern Iraq between 2007 and 2009. This data is used as an independent validation of a hydrologic model of the region including lake mass variations. We developed a rainfall–runoff model for five tributaries of the Tigris River, based on local geology and climate conditions. Model inputs are precipitation from Tropical Rainfall Measurement Mission (TRMM observations, and potential evaporation from GLDAS model parameters. Our model includes a representation of the karstified aquifers that cause large natural groundwater variations in this region. Observed river discharges were used to calibrate our model. In order to get the total mass variations, we corrected for lake mass variations derived from Moderate Resolution Imaging Spectroradiometer (MODIS in combination with satellite altimetry and some in-situ data. Our rainfall–runoff model confirms that Northern Iraq suffered a drought between 2007 and 2009 and is consistent with the mass loss observed by GRACE over that period. Also, GRACE observed the annual cycle predicted by the rainfall–runoff model. The total mass depletion seen by GRACE between 2007 and 2009 is mainly explained by a lake mass depletion of 74 ± 4 mm and a natural groundwater depletion of 37 ± 6 mm. Our findings indicate that man-made groundwater extraction has a minor influence in this region while depletion of lake mass and geology play a key role.

  10. Depletion of mitochondria in mammalian cells through enforced mitophagy.

    Science.gov (United States)

    Correia-Melo, Clara; Ichim, Gabriel; Tait, Stephen W G; Passos, João F

    2017-01-01

    Mitochondria are not only the 'powerhouse' of the cell; they are also involved in a multitude of processes that include calcium storage, the cell cycle and cell death. Traditional means of investigating mitochondrial importance in a given cellular process have centered upon depletion of mtDNA through chemical or genetic means. Although these methods severely disrupt the mitochondrial electron transport chain, mtDNA-depleted cells still maintain mitochondria and many mitochondrial functions. Here we describe a straightforward protocol to generate mammalian cell populations with low to nondetectable levels of mitochondria. Ectopic expression of the ubiquitin E3 ligase Parkin, combined with short-term mitochondrial uncoupler treatment, stimulates widespread mitophagy and effectively eliminates mitochondria. In this protocol, we explain how to generate Parkin-expressing, mitochondria-depleted cells from scratch in 23 d, as well as offer a variety of methods for confirming mitochondrial clearance. Furthermore, we describe culture conditions to maintain mitochondrial-depleted cells for up to 30 d with minimal loss of viability, for longitudinal studies. This method should prove useful for investigating the importance of mitochondria in a variety of biological processes.

  11. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Alhonen, Leena [Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio (Finland); School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio (Finland); Salonurmi, Tuire; Savolainen, Markku J. [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland)

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  12. A mass spectrometric method to determine activities of enzymes involved in polyamine catabolism

    Energy Technology Data Exchange (ETDEWEB)

    Moriya, Shunsuke; Iwasaki, Kaori [Department of Molecular Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo 156-8506 (Japan); Samejima, Keijiro, E-mail: samejima-kj@igakuken.or.jp [Department of Molecular Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo 156-8506 (Japan); Takao, Koichi [Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295 (Japan); Kohda, Kohfuku [Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo 202-8585 (Japan); Hiramatsu, Kyoko; Kawakita, Masao [Department of Molecular Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo 156-8506 (Japan)

    2012-10-20

    Highlights: Black-Right-Pointing-Pointer Compounds in polyamine catabolic pathway were determined by a column-free ESI-TOF MS. Black-Right-Pointing-Pointer N{sup 1}- and N{sup 8}-acetylspermidine were determined by a column-free ESI-MS/MS. Black-Right-Pointing-Pointer The method was applied to determine activities of APAO, SMO, and SSAT in the pathway. Black-Right-Pointing-Pointer The assay method contained stable isotope-labeled natural substrates. Black-Right-Pointing-Pointer It is applicable to biological samples containing natural substrate and product. - Abstract: An analytical method for the determination of three polyamines (putrescine, spermidine, and spermine) and five acetylpolyamines [N{sup 1}-acetylspermidine (N{sup 1}AcSpd), N{sup 8}-acetylspermidine (N{sup 8}AcSpd), N{sup 1}-acetylspermine, N{sup 1},N{sup 8}-diacetylspermidine, and N{sup 1},N{sup 12}-diacetylspermine] involved in the polyamine catabolic pathway has been developed using a hybrid tandem mass spectrometer. Heptafluorobutyryl (HFB) derivatives of these compounds and respective internal standards labeled with stable isotopes were analyzed simultaneously by TOF MS, based on peak areas appearing at appropriate m/z values. The isomers, N{sup 1}AcSpd and N{sup 8}AcSpd were determined from their fragment ions, the acetylamidopropyl and acetylamidobutyl groups, respectively, using MS/MS with {sup 13}C{sub 2}-N{sup 1}AcSpd and {sup 13}C{sub 2}-N{sup 8}AcSpd which have the {sup 13}C{sub 2}-acetyl group as an internal standard. The TOF MS method was successfully applied to measure the activity of enzymes involved in polyamine catabolic pathways, namely N{sup 1}-acetylpolyamine oxidase (APAO), spermine oxidase (SMO), and spermidine/spermine N{sup 1}-acetyltransferase (SSAT). The following natural substrates and products labeled with stable isotopes considering the application to biological samples were identified; for APAO, [4,9,12-{sup 15}N{sub 3}]-N{sup 1}-acetylspermine and [1,4,8-{sup 15}N{sub 3

  13. High homocysteine induces betaine depletion.

    Science.gov (United States)

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.

  14. Specification for the VERA Depletion Benchmark Suite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  15. Ozone Depletion Potential of CH3Br

    Science.gov (United States)

    Sander, Stanley P.; Ko, Malcolm K. W.; Sze, Nien Dak; Scott, Courtney; Rodriquez, Jose M.; Weisenstein, Debra K.

    1998-01-01

    The ozone depletion potential (ODP) of methyl bromide (CH3Br) can be determined by combining the model-calculated bromine efficiency factor (BEF) for CH3Br and its atmospheric lifetime. This paper examines how changes in several key kinetic data affect BEF. The key reactions highlighted in this study include the reaction of BrO + H02, the absorption cross section of HOBr, the absorption cross section and the photolysis products of BrON02, and the heterogeneous conversion of BrON02 to HOBR and HN03 on aerosol particles. By combining the calculated BEF with the latest estimate of 0.7 year for the atmospheric lifetime of CH3Br, the likely value of ODP for CH3Br is 0.39. The model-calculated concentration of HBr (approximately 0.3 pptv) in the lower stratosphere is substantially smaller than the reported measured value of about I pptv. Recent publications suggested models can reproduce the measured value if one assumes a yield for HBr from the reaction of BrO + OH or from the reaction of BrO + H02. Although the DeAlore et al. evaluation concluded any substantial yield of HBr from BrO + HO2 is unlikely, for completeness, we calculate the effects of these assumed yields on BEF for CH3Br. Our calculations show that the effects are minimal: practically no impact for an assumed 1.3% yield of HBr from BrO + OH and 10% smaller for an assumed 0.6% yield from BrO + H02.

  16. Transforming a drug/H+ antiporter into a polyamine importer by a single mutation.

    Science.gov (United States)

    Brill, Shlomo; Falk, Ofir Sade; Schuldiner, Shimon

    2012-10-16

    EmrE, a multidrug antiporter from Escherichia coli, has presented biochemists with unusual surprises. Here we describe the transformation of EmrE, a drug/H(+) antiporter to a polyamine importer by a single mutation. Antibiotic resistance in microorganisms may arise by mutations at certain chromosomal loci. To investigate this phenomenon, we used directed evolution of EmrE to assess the rate of development of novel specificities in existing multidrug transporters. Strikingly, when a library of random mutants of EmrE was screened for resistance to two major antibacterial drugs--norfloxacin, a fluoroquinolone, and erythromycin, a macrolide--proteins with single mutations were found capable of conferring resistance. The mutation conferring erythromycin resistance resulted from substitution of a fully conserved and essential tryptophan residue to glycine, and, as expected, this protein lost its ability to recognize and transport the classical EmrE substrates. However, this protein functions now as an electrochemical potential driven importer of a new set of substrates: aliphatic polyamines. This mutant provides a unique paradigm to understand the function and evolution of distinct modes of transport.

  17. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis.

    Science.gov (United States)

    Goodwin, Andrew C; Destefano Shields, Christina E; Wu, Shaoguang; Huso, David L; Wu, XinQun; Murray-Stewart, Tracy R; Hacker-Prietz, Amy; Rabizadeh, Shervin; Woster, Patrick M; Sears, Cynthia L; Casero, Robert A

    2011-09-13

    It is estimated that the etiology of 20-30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis (ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purified B. fragilis toxin (BFT) up-regulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent generation of ROS and induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6 mice is associated with increased SMO expression and treatment of mice with an inhibitor of polyamine catabolism, N(1),N(4)-bis(2,3-butandienyl)-1,4-butanediamine (MDL 72527), significantly reduces ETBF-induced chronic inflammation and proliferation. Most importantly, in the multiple intestinal neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon tumorigenesis by 69% (P < 0.001). The results of these studies indicate that SMO is a source of bacteria-induced ROS directly associated with tumorigenesis and could serve as a unique target for chemoprevention.

  18. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis

    Science.gov (United States)

    Goodwin, Andrew C.; Shields, Christina E. Destefano; Wu, Shaoguang; Huso, David L.; Wu, XinQun; Murray-Stewart, Tracy R.; Hacker-Prietz, Amy; Rabizadeh, Shervin; Woster, Patrick M.; Sears, Cynthia L.; Casero, Robert A.

    2011-01-01

    It is estimated that the etiology of 20–30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis (ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purified B. fragilis toxin (BFT) up-regulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent generation of ROS and induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6 mice is associated with increased SMO expression and treatment of mice with an inhibitor of polyamine catabolism, N1,N4-bis(2,3-butandienyl)-1,4-butanediamine (MDL 72527), significantly reduces ETBF-induced chronic inflammation and proliferation. Most importantly, in the multiple intestinal neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon tumorigenesis by 69% (P < 0.001). The results of these studies indicate that SMO is a source of bacteria-induced ROS directly associated with tumorigenesis and could serve as a unique target for chemoprevention. PMID:21876161

  19. Genome wide association mapping for the tolerance to the polyamine oxidase inhibitor guazatine in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Kostadin Evgeniev eAtanasov

    2016-04-01

    Full Text Available Guazatine is a potent inhibitor of polyamine oxidase (PAO activity. In agriculture, guazatine is used as non-systemic contact fungicide efficient in the protection of cereals and citrus fruits against disease. The composition of guazatine is complex, mainly constituted by a mixture of synthetic guanidated polyamines (polyaminoguanidines. Here we have studied the effects from exposure to guazatine in the weed Arabidopsis thaliana. We report that micromolar concentrations of guazatine are sufficient to inhibit growth of Arabidopsis seedlings and induce chlorosis, whereas germination is barely affected. We observed the occurrence of quantitative variation in the response to guazatine between 107 randomly chosen Arabidopsis accessions. This enabled us to undertake genome-wide association (GWA mapping that identified a locus on chromosome one associated with guazatine tolerance. CHLOROPHYLLASE 1 (CLH1 within this locus was studied as candidate gene, together with its paralog (CLH2. The analysis of independent clh1-2, clh1-3, clh2-3, clh2-2 and double clh1-2 clh2-3 mutant alleles indicated that CLH1 and/or CLH2 loss-of-function or expression down-regulation promote guazatine tolerance in Arabidopsis. We report a natural mechanism by which Arabidopsis populations can overcome toxicity by the fungicide guazatine.

  20. Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl polyamine derivatives.

    Science.gov (United States)

    Pavlov, V; Kong Thoo Lin, P; Rodilla, V

    2001-07-31

    Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.

  1. Phenotypic comparison of samdc and spe mutants reveals complex relationships of polyamine metabolism in Ustilago maydis.

    Science.gov (United States)

    Valdés-Santiago, Laura; Cervantes-Chávez, José Antonio; Winkler, Robert; León-Ramírez, Claudia G; Ruiz-Herrera, José

    2012-03-01

    Synthesis of spermidine involves the action of two enzymes, spermidine synthase (Spe) and S-adenosylmethionine decarboxylase (Samdc). Previously we cloned and disrupted the gene encoding Spe as a first approach to unravel the biological function of spermidine in Ustilago maydis. With this background, the present study was designed to provide a better understanding of the role played by Samdc in the regulation of the synthesis of this polyamine. With this aim we proceeded to isolate and delete the gene encoding Samdc from U. maydis, and made a comparative analysis of the phenotypes of samdc and spe mutants. Both spe and samdc mutants behaved as spermidine auxotrophs, and were more sensitive than the wild-type strain to different stress conditions. However, the two mutants displayed significant differences: in contrast to spe mutants, samdc mutants were more sensitive to LiCl stress, high spermidine concentrations counteracted their dimorphic deficiency, and they were completely avirulent. It is suggested that these differences are possibly related to differences in exogenous spermidine uptake or the differential location of the respective enzymes in the cell. Alternatively, since samdc mutants accumulate higher levels of S-adenosylmethionine (SAM), whereas spe mutants accumulate decarboxylated SAM, the known opposite roles of these metabolites in the processes of methylation and differentiation offer an additional attractive hypothesis to explain the phenotypic differences of the two mutants, and provide insights into the additional roles of polyamine metabolism in the physiology of the cell.

  2. Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell.

    Science.gov (United States)

    Miller-Fleming, Leonor; Olin-Sandoval, Viridiana; Campbell, Kate; Ralser, Markus

    2015-10-23

    The polyamines (PAs) spermidine, spermine, putrescine and cadaverine are an essential class of metabolites found throughout all kingdoms of life. In this comprehensive review, we discuss their metabolism, their various intracellular functions and their unusual and conserved regulatory features. These include the regulation of translation via upstream open reading frames, the over-reading of stop codons via ribosomal frameshifting, the existence of an antizyme and an antizyme inhibitor, ubiquitin-independent proteasomal degradation, a complex bi-directional membrane transport system and a unique posttranslational modification-hypusination-that is believed to occur on a single protein only (eIF-5A). Many of these features are broadly conserved indicating that PA metabolism is both concentration critical and evolutionary ancient. When PA metabolism is disrupted, a plethora of cellular processes are affected, including transcription, translation, gene expression regulation, autophagy and stress resistance. As a result, the role of PAs has been associated with cell growth, aging, memory performance, neurodegenerative diseases, metabolic disorders and cancer. Despite comprehensive studies addressing PAs, a unifying concept to interpret their molecular role is missing. The precise biochemical function of polyamines is thus one of the remaining mysteries of molecular cell biology.

  3. Polyamine metabolism and osmotic stress. II. Improvement of oat protoplasts by an inhibitor of arginine decarboxylase.

    Science.gov (United States)

    Tiburcio, A F; Kaur-Sawhney, R; Galston, A W

    1986-01-01

    We have attempted to improve the viability of cereal mesophyll protoplasts by pretreatment of leaves with DL-alpha-difluoromethylarginine (DFMA), a specific 'suicide' inhibitor of the enzyme (arginine decarboxylase) responsible for their osmotically induced putrescine accumulation. Leaf pretreatment with DFMA before a 6 hour osmotic shock caused a 45% decrease of putrescine and a 2-fold increase of spermine titer. After 136 hours of osmotic stress, putrescine titer in DFMA-pretreated leaves increased by only 50%, but spermidine and spermine titers increased dramatically by 3.2- and 6-fold, respectively. These increases in higher polyamines could account for the reduced chlorophyll loss and enhanced ability of pretreated leaves to incorporate tritiated thymidine, uridine, and leucine into macromolecules. Pretreatment with DFMA significantly improved the overall viability of the protoplasts isolated from these leaves. The results support the view that the osmotically induced rise in putrescine and blockage of its conversion to higher polyamines may contribute to the lack of sustained cell division in cereal mesophyll protoplasts, although other undefined factors must also play a major role.

  4. Flocculation performance of epichlorohydrin-dimethylamine polyamine in treating dyeing wastewater.

    Science.gov (United States)

    Wang, Yuanfang; Gao, Baoyu; Yue, Qinyan; Zhan, Xiao; Si, Xiaohui; Li, Chunxiao

    2009-01-01

    Epichlorohydrin-dimethylamine polymers with different intrinsic viscosity (eta) and cationicity (tau) were synthesized. The flocculation performance and mechanism of these polymers in the removal of the reactive and disperse dyes from synthetic wastewater was investigated in terms of flocculation dynamics and color removal efficiency. The polymer flocculation efficiency was compared with that of polyaluminum chloride (PAC) and a composite flocculant based on polyaluminum chloride-epichlorohydrin-dimethylamine polyamine. The results showed that epichlorohydrin-dimethylamine polymer was effective over a pH range of 2-10 for the reactive and disperse dye removal (Reactive Brilliant Red and Disperse Yellow dyes). Epichlorohydrin-dimethylamine polymer with the highest eta and tau gave the best reactive dye removal efficiency, and its adsorption-bridging and electric neutralization ability played important roles in the flocculation process. The higher the eta viscosity of the epichlorohydrin-dimethylamine polymer, the better the flocculation performance of epichlorohydrin-dimethylamine polyamine, and stronger adsorption-bridging ability was obtained for removing the disperse dye from dyeing wastewaters. Epichlorohydrin-dimethylamine polymer achieved better decolorization performance when used together with PAC.

  5. Life without putrescine: disruption of the gene-encoding polyamine oxidase in Ustilago maydis odc mutants.

    Science.gov (United States)

    Valdés-Santiago, Laura; Guzmán-de-Peña, Doralinda; Ruiz-Herrera, José

    2010-11-01

    In previous communications the essential role of spermidine in Ustilago maydis was demonstrated by means of the disruption of the genes encoding ornithine decarboxylase (ODC) and spermidine synthase (SPE). However, the assignation of specific roles to each polyamine in different cellular functions was not possible because the spermidine added to satisfy the auxotrophic requirement of odc/spe double mutants is partly back converted into putrescine. In this study, we have approached this problem through the disruption of the gene-encoding polyamine oxidase (PAO), required for the conversion of spermidine into putrescine, and the construction of odc/pao double mutants that were unable to synthesize putrescine by either ornithine decarboxylation or retroconversion from spermidine. Phenotypic analysis of the mutants provided evidence that putrescine is only an intermediary in spermidine biosynthesis, and has no direct role in cell growth, dimorphic transition, or any other vital function of U. maydis. Nevertheless, our results show that putrescine may play a role in the protection of U. maydis against salt and osmotic stress, and possibly virulence. Evidence was also obtained that the retroconversion of spermidine into putrescine is not essential for U. maydis growth but may be important for its survival under natural conditions.

  6. Interaction of polyamines with proteins of photosystem II: Cation binding and photosynthetic oxygen evolution

    Science.gov (United States)

    Beauchemin, R.; Harnois, J.; Rouillon, R.; Tajmir-Riahi, H. A.; Carpentier, R.

    2007-05-01

    Polyamines are organic cations that function in diverse physiological processes that share as a common thread a close relationship to cell proliferation and growth. Polyamines also affect photosynthetic oxygen evolution and therefore, this study was designed to investigate the interaction of 1,3-diaminopropane, 1,4-diaminobutane (putrescine), and 1,5-diaminopentane (cadaverine) cations with proteins of photosystem II (PSII) using PSII-enriched submembrane fractions with diamine concentrations between 0.01 and 20 mM. Fourier transformed infrared (FTIR) difference spectroscopy with its self-deconvolution and second derivative resolution enhancement, as well as curve-fitting procedures were applied in order to determine the diamine binding mode, the protein conformational changes, and the structural properties of diamine-protein complexes. Spectroscopic evidence showed that diamines interact with proteins (H-bonding) through polypeptide C dbnd O groups with no major perturbations of protein secondary structure. At very low diamine concentration (0.01 mM), no inhibition of oxygen-evolution occurred, while at higher diamine content (5-10 mM), 100% inhibition was observed. Chorophyll fluorescence measurements demonstrated that the inhibition mainly affects the oxygen evolving complex of PSII. Comparisons of the effects of these dipositive organic cations with divalent metal cations on one hand and with polyvalent spermine and spermidine on the other hand, show major alterations of the protein secondary structure as positive charge increases.

  7. Structure-activity relationship study of spider polyamine toxins as inhibitors of ionotropic glutamate receptors.

    Science.gov (United States)

    Xiong, Xiao-Feng; Poulsen, Mette H; Hussein, Rama A; Nørager, Niels G; Strømgaard, Kristian

    2014-12-01

    The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recently found to be very potent open-channel blockers of ionotropic glutamate (iGlu) receptors. In this study we designed and synthesized a collection of 24 analogues of these toxins using a recently developed solid-phase synthetic methodology. Systematic variation in two regions of the toxins and subsequent evaluation of biological activity at AMPA and NMDA subtypes of iGlu receptors provided succinct information on structure-activity relationships. In particular, one set of analogues were found to display exquisite selectivity and potency for AMPA receptors relative to the natural products. Thus, this systematic SAR study has provided new pharmacological tools for studies of iGlu receptors.

  8. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.

    Science.gov (United States)

    Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Martín-Martín, Natalia; Fernandez-Ruiz, Sonia; Sutherland, James D; Clasquin, Michelle; Tomas-Cortazar, Julen; Jimenez, Jose; Torres, Ines; Quang, Phong; Ximenez-Embun, Pilar; Bago, Ruzica; Ugalde-Olano, Aitziber; Loizaga-Iriarte, Ana; Lacasa-Viscasillas, Isabel; Unda, Miguel; Torrano, Verónica; Cabrera, Diana; van Liempd, Sebastiaan M; Cendon, Ylenia; Castro, Elena; Murray, Stuart; Revandkar, Ajinkya; Alimonti, Andrea; Zhang, Yinan; Barnett, Amelia; Lein, Gina; Pirman, David; Cortazar, Ana R; Arreal, Leire; Prudkin, Ludmila; Astobiza, Ianire; Valcarcel-Jimenez, Lorea; Zuñiga-García, Patricia; Fernandez-Dominguez, Itziar; Piva, Marco; Caro-Maldonado, Alfredo; Sánchez-Mosquera, Pilar; Castillo-Martín, Mireia; Serra, Violeta; Beraza, Naiara; Gentilella, Antonio; Thomas, George; Azkargorta, Mikel; Elortza, Felix; Farràs, Rosa; Olmos, David; Efeyan, Alejo; Anguita, Juan; Muñoz, Javier; Falcón-Pérez, Juan M; Barrio, Rosa; Macarulla, Teresa; Mato, Jose M; Martinez-Chantar, Maria L; Cordon-Cardo, Carlos; Aransay, Ana M; Marks, Kevin; Baselga, José; Tabernero, Josep; Nuciforo, Paolo; Manning, Brendan D; Marjon, Katya; Carracedo, Arkaitz

    2017-07-06

    Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program.

  9. Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines.

    Science.gov (United States)

    Mony, Laetitia; Zhu, Shujia; Carvalho, Stéphanie; Paoletti, Pierre

    2011-06-17

    NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands. While much has been learned recently regarding allosteric inhibition of NMDARs, the structural determinants underlying positive allosteric modulation of these receptors remain poorly defined. Here, we show that polyamines, naturally occurring polycations that selectively enhance NMDARs containing the GluN2B subunit, bind at a dimer interface between GluN1 and GluN2B subunit N-terminal domains (NTDs). Polyamines act by shielding negative charges present on GluN1 and GluN2B NTD lower lobes, allowing their close apposition, an effect that in turn prevents NTD clamshell closure. Our work reveals the mechanistic basis for positive allosteric modulation of NMDARs. It provides the first example of an intersubunit binding site in this class of receptors, a discovery that holds promise for future drug interventions.

  10. Effect of retinoic acid on proliferation and polyamine metabolism in cultured bovine retinal pigment epithelial cells.

    Science.gov (United States)

    Yasunari, T; Yanagihara, N; Komatsu, T; Moriwaki, M; Shiraki, K; Miki, T; Yano, Y; Otani, S

    1999-01-01

    Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 microM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.

  11. DNA-HMGB1 interaction: The nuclear aggregates of polyamine mediation.

    Science.gov (United States)

    Iacomino, Giuseppe; Picariello, Gianluca; Sbrana, Francesca; Raiteri, Roberto; D'Agostino, Luciano

    2016-10-01

    Nuclear aggregates of polyamines (NAPs) are supramolecular compounds generated by the self-assembly of protonated nuclear polyamines (spermine, spermidine and putrescine) and phosphate ions. In the presence of genomic DNA, the hierarchical process of self-structuring ultimately produces nanotube-like polymers that envelop the double helix. Because of their modular nature and their aggregation-disaggregation dynamics, NAPs confer plasticity and flexibility to DNA. Through the disposition of charges, NAPs also enable a bidirectional stream of information between the genome and interacting moieties. High mobility group (HMG) B1 is a non-histone chromosomal protein that binds to DNA and that influences multiple nuclear processes. Because genomic DNA binds to either NAPs or HMGB1 protein, we explored the ability of in vitro self-assembled NAPs (ivNAPs) to mediate the DNA-HMGB1 interaction. To this end, we structured DNA-NAPs-HMGB1 and DNA-HMGB1-NAPs ternary complexes in vitro through opportune sequential incubations. Mobility shift electrophoresis and atomic force microscopy showed that the DNA-ivNAPs-HGMB1 complex had conformational assets supposedly more suitable those of the DNA-HGMB1-ivNAPs to comply with the physiological and functional requirements of DNA. Our findings indicated that ivNAPs act as mediators of the DNA-HMGB1 interaction.

  12. Possible ozone depletions following nuclear explosions

    Science.gov (United States)

    Whitten, R. C.; Borucki, W. J.; Turco, R. P.

    1975-01-01

    The degree of depletion of the ozone layer ensuing after delivery of strategic nuclear warheads (5000 and 10,000 Mton) due to production of nitrogen oxides is theoretically assessed. Strong depletions are calculated for 16-km and 26-km altitudes, peaking 1-2 months after detonation and lasting for three years, while a significant depletion at 36 km would peak after one year. Assuming the explosions occur between 30 and 70 deg N, these effects should be much more pronounced in this region than over the Northern Hemisphere as a whole. It is concluded that Hampson's concern on this matter (1974) is well-founded.-

  13. CsPAO4 of Citrus sinensis functions in polyamine terminal catabolism and inhibits plant growth under salt stress.

    Science.gov (United States)

    Wang, Wei; Liu, Ji-Hong

    2016-08-18

    Polyamine oxidase (PAO) is a key enzyme catalyzing polyamine catabolism leading to H2O2 production. We previously demonstrated that Citrus sinensis contains six putative PAO genes, but their functions are not well understood. In this work, we reported functional elucidation of CsPAO4 in polyamine catabolism and salt stress response. CsPAO4 was localized to the apoplast and used both spermidine (Spd) and spermine (Spm) as substrates for terminal catabolism. Transgenic plants overexpressing CsPAO4 displayed prominent increase in PAO activity, concurrent with marked decrease of Spm and Spd and elevation of H2O2. Seeds of transgenic lines displayed better germination when compared with wild type (WT) under salt stress. However, both vegetative growth and root elongation of the transgenic lines were prominently inhibited under salt stress, accompanied by higher level of H2O2 and more conspicuous programmed cell death (PCD). Exogenous supply of catalase (CAT), a H2O2 scavenger, partially recovered the vegetative growth and root elongation. In addition, spermine inhibited root growth of transgenic plants. Taken together, these data demonstrated that CsPAO4 accounts for production of H2O2 causing oxidative damages under salt stress and that down-regulation of a PAO gene involved in polyamine terminal catabolism may be an alternative approach for improving salt stress tolerance.

  14. Genome-wide identification and expression analysis of the polyamine oxidase gene family in sweet orange (Citrus sinensis).

    Science.gov (United States)

    Wang, Wei; Liu, Ji-Hong

    2015-01-25

    Polyamine oxidases (PAOs) are FAD-dependent enzymes associated with polyamine catabolism. In plants, increasing evidences support that PAO genes play essential roles in abiotic and biotic stresses response. In this study, six putative PAO genes (CsPAO1-CsPAO6) were unraveled in sweet orange (Citrus sinensis) using the released citrus genome sequences. A total of 203 putative cis-regulatory elements involved in hormone and stress response were predicted in 1.5-kb promoter regions at the upstream of CsPAOs. The CsPAOs can be divided into four major groups, with similar organizations with their counterparts of Arabidopsis thaliana. Transcripts of CsPAOs were detected in leaf, stem, cotyledon, and root, with the highest levels detected in the roots. The CsPAOs displayed various responses to exogenous treatments with polyamines and ABA and were differentially altered by abiotic stresses, including cold, salt, and mannitol. Overexpression of CsPAO3 in tobacco demonstrated that spermidine and spermine were decreased in the transgenic line, while putrescine was significantly enhanced, implying a potential role of this gene in polyamine back conversion. These data provide valuable knowledge for understanding the roles of the PAO genes in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Fast Fourier Transform IR Characterization of Epoxy GY Systems Crosslinked with Aliphatic and Cycloaliphatic EH Polyamine Adducts

    Directory of Open Access Journals (Sweden)

    Caslav Lacnjevac

    2010-01-01

    Full Text Available The use of fast FT-IR spectroscopy as a sensitive method to estimate a change of the crosslinking kinetics of epoxy resin with polyamine adducts is described in this study. A new epoxy formulation based on the use of polyamine adducts as the hardeners was analyzed. Crosslinking reactions of the different stoichiometric mixtures of the unmodified GY250 epoxy resin with the aliphatic EH606 and the cycloaliphatic EH637 polyamine adducts were studied using mid FT-IR spectroscopic techniques. As the crosslinking proceeded, the primary amine groups in polyamine adduct are converted to secondary and the tertiary amines. The decrease in the IR band intensity of epoxy groups at about 915 cm-1, as well as at about 3,056 cm-1, was observed due to process. Mid IR spectral analysis was used to calculate the content of the epoxy groups as a function of crosslinking time and the crosslinking degree of resin. The amount of all the epoxy species was estimated from IR spectra to changes during the crosslinking kinetics of epichlorhydrin.

  16. Cissus quadrangularis L. extract attenuates chronic ulcer by possible involvement of polyamines and proliferating cell nuclear antigen

    Directory of Open Access Journals (Sweden)

    Mallika Jainu

    2010-01-01

    Full Text Available The present study was designed to investigate whether Cissus quandrangularis extract (CQE had healing effects on gastric ulcer, through modulation of polyamines and proliferating cell nuclear antigen (PCNA in rats. Administration of acetic acid (AA was accompanied by reduced PCNA which was determined by immunohistochemical staining, 3 H-thymidine incorporation using liquid scintillation spectrometry, mitochondrial marker enzymes, polyamine contents and transforming growth factor-alpha (TGF-a expression in gastric mucosa of rats. Administration of CQE after the application of AA to the stomach enhanced the reduction of ulcer area in a dose-dependent manner which was confirmed by histoarchitecture. Moreover, CQE significantly increased the 3 H-thymidine incorporation and the levels of polyamines such as putrescine, spermine and spermidine in ulcerated rats. In addition, the extract offers gastroprotection in the ulcerated area by increased expression of TGF-a and also reversed the changes in the gastric mucosa of ulcerated rats with significant elevation in mitochondrial tricarboxylic acid (TCA cycle enzymes and PCNA levels. Based on these results, the healing effect of CQE on AA induced gastric mucosal injury in rats may be attributed to its growth promoting and cytoprotective actions, possibly involving an increase in tissue polyamine contents and cell proliferation.

  17. Fast Fourier Transform IR Characterization of Epoxy GY Systems Crosslinked with Aliphatic and Cycloaliphatic EH Polyamine Adducts

    Science.gov (United States)

    Nikolic, Goran; Zlatkovic, Sasa; Cakic, Milorad; Cakic, Suzana; Lacnjevac, Caslav; Rajic, Zoran

    2010-01-01

    The use of fast FT-IR spectroscopy as a sensitive method to estimate a change of the crosslinking kinetics of epoxy resin with polyamine adducts is described in this study. A new epoxy formulation based on the use of polyamine adducts as the hardeners was analyzed. Crosslinking reactions of the different stoichiometric mixtures of the unmodified GY250 epoxy resin with the aliphatic EH606 and the cycloaliphatic EH637 polyamine adducts were studied using mid FT-IR spectroscopic techniques. As the crosslinking proceeded, the primary amine groups in polyamine adduct are converted to secondary and the tertiary amines. The decrease in the IR band intensity of epoxy groups at about 915 cm−1, as well as at about 3,056 cm−1, was observed due to process. Mid IR spectral analysis was used to calculate the content of the epoxy groups as a function of crosslinking time and the crosslinking degree of resin. The amount of all the epoxy species was estimated from IR spectra to changes during the crosslinking kinetics of epichlorhydrin. PMID:22315562

  18. Polar stratospheric clouds and ozone depletion

    Science.gov (United States)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  19. [Hepatomioneuropathy secondary to mitochondrial DNA depletion].

    Science.gov (United States)

    Blanco-Barca, M O; Gómez-Lado, C; Campos-González, Y; Castro-Gago, M

    2007-04-01

    Mitochondrial DNA depletion (mtDNA) is an highly heterogeneous condition characterized by a decreased number of mtDNA copies. The patient is a 22-month-old girl with generalized hypotonia, marked weakness, respiratory failure, arterial hypertension, hyperlactacidemia, hepatosplenomegaly and mild hypertransaminasemia without hepatic failure neither hypoketotic hypoglycemia. Electromyographic findings were consistent with neuromyopathy and muscle biopsy suggested a neurogenic atrophy. Electron microscopy revealed lipid droplets, subsarcolemmal accumulation of mitochondrias and glycogen granules. Respiratory chain enzime activities were normal. Genetic study in muscle showed mtDNA depletion, and the diagnosis of spinal muscular atrophy caused by survival motoneuron gene deletion was excluded. This case might be a novel phenotype of mtDNA depletion which could be named hepatomioneuropatyc form. A normal result of respiratory chain enzimes in muscle doesn't excluded mtDNA depletion.

  20. 3D-Membrane Stacks on Supported Membranes Composed of Diatom Lipids Induced by Long-Chain Polyamines.

    Science.gov (United States)

    Gräb, Oliver; Abacilar, Maryna; Daus, Fabian; Geyer, Armin; Steinem, Claudia

    2016-10-04

    Long-chain polyamines (LCPAs) are intimately involved in the biomineralization process of diatoms taking place in silica deposition vesicles being acidic compartments surrounded by a lipid bilayer. Here, we addressed the question whether and how LCPAs interact with lipid membranes composed of glycerophospholipids and glyceroglycolipids mimicking the membranes of diatoms and higher plants. Solid supported lipid bilayers and monolayers containing the three major components that are unique in diatoms and higher plants, i.e., monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and sulfoquinovosyldiacylglycerol (SQDG), were prepared by spreading small unilamellar vesicles. The integrity of the membranes was investigated by fluorescence microscopy and atomic force microscopy showing continuous flat bilayers and monolayers with small protrusions on top of the membrane. The addition of a synthetic polyamine composed of 13 amine groups separated by a propyl spacer (C3N13) results in flat but three-dimensional membrane stacks within minutes. The membrane stacks are connected with the underlying membrane as verified by fluorescence recovery after photobleaching experiments. Membrane stack formation was found to be independent of the lipid composition; i.e., neither glyceroglycolipids nor negatively charged lipids were required. However, the formation process was strongly dependent on the chain length of the polyamine. Whereas short polyamines such as the naturally occurring spermidine, spermine, and the synthetic polyamines C3N4 and C3N5 do not induce stack formation, those containing seven and more amine groups (C3N7, C3N13, and C3N18) do form membrane stacks. The observed stack formation might have implications for the stability and expansion of the silica deposition vesicle during valve and girdle band formation in diatoms.

  1. Enhanced polyamine accumulation alters carotenoid metabolism at the transcriptional level in tomato fruit over-expressing spermidine synthase.

    Science.gov (United States)

    Neily, Mohamed Hichem; Matsukura, Chiaki; Maucourt, Mickaël; Bernillon, Stéphane; Deborde, Catherine; Moing, Annick; Yin, Yong-Gen; Saito, Takeshi; Mori, Kentaro; Asamizu, Erika; Rolin, Dominique; Moriguchi, Takaya; Ezura, Hiroshi

    2011-02-15

    Polyamines are involved in crucial plant physiological events, but their roles in fruit development remain unclear. We generated transgenic tomato plants that show a 1.5- to 2-fold increase in polyamine content by over-expressing the spermidine synthase gene, which encodes a key enzyme for polyamine biosynthesis. Pericarp-columella and placental tissue from transgenic tomato fruits were subjected to (1)H-nuclear magnetic resonance (NMR) for untargeted metabolic profiling and high-performance liquid chromatography-diode array detection for carotenoid profiling to determine the effects of high levels of polyamine accumulation on tomato fruit metabolism. A principal component analysis of the quantitative (1)H NMR data from immature green to red ripe fruit showed a clear discrimination between developmental stages, especially during ripening. Quantification of 37 metabolites in pericarp-columella and 41 metabolites in placenta tissues revealed distinct metabolic profiles between the wild type and transgenic lines, particularly at the late ripening stages. Notably, the transgenic tomato fruits also showed an increase in carotenoid accumulation, especially in lycopene (1.3- to 2.2-fold), and increased ethylene production (1.2- to 1.6-fold) compared to wild-type fruits. Genes responsible for lycopene biosynthesis, including phytoene synthase, phytoene desaturase, and deoxy-d-xylulose 5-phosphate synthase, were significantly up-regulated in ripe transgenic fruits, whereas genes involved in lycopene degradation, including lycopene-epsilon cyclase and lycopene beta cyclase, were down-regulated in the transgenic fruits compared to the wild type. These results suggest that a high level of accumulation of polyamines in the tomato regulates the steady-state level of transcription of genes responsible for the lycopene metabolic pathway, which results in a higher accumulation of lycopene in the fruit.

  2. Temporal Dynamics of Antioxidant Defence System in Relation to Polyamine Catabolism in Rice under Direct-Seeded and Transplanted Conditions

    Institute of Scientific and Technical Information of China (English)

    Manisha KUMARI; Bavita ASTHIR; Navtej Singh BAINS

    2014-01-01

    Six rice cultivars viz. PR120, PR116, Feng Ai Zan, PR115, PAU201 and Punjab Mehak 1 under the direct-seeded and transplanted conditions were used to investigate the involvement of antioxidative defence system in relation to polyamine catabolism in temporal regulation of developing grains. Activities of ascorbate peroxidase (APx), guaiacol peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), polyamine oxidases (PAO) and contents of ascorbate,α-tocopherol, proline and polyamines increased gradually until mid-milky stage and then declined towards maturity stage under both planting conditions. The transplanted condition led to higher activities of antioxidative enzymes (APx, GPx and CAT) and contents of ascorbate,α-tocopherol and proline whereas the direct-seeded condition had elevated levels of PAO and SOD activities and contents of polyamines, lipid peroxide and hydrogen peroxide. Cultivars Feng Ai Zan and PR120 exhibited superior tolerance over other cultivars by accumulating higher contents of ascorbate,α-tocopherol and proline with increasing level of PAO and SOD activities under the direct-seeded condition. However, under the transplanted condition PR116 and PAU201 showed higher activities of antioxidative enzymes with decreasing content of lipid peroxide. Therefore, we concluded that under the direct-seeded condition, enhancements of polyamines content and PAO activity enabled rice cultivars more tolerant to oxidative stress, while under the transplanted condition, antioxidative defence with decreasing of lipid peroxide content was closely associated with the protection of grains by maintaining membrane integrity during rice grain filling. The results indicated that temporal dynamics of H2O2 metabolic machinery was strongly up-regulated especially at the mid-milky stage.

  3. Activity of peroxisomal enzymes, and levels of polyamines in LPA-transgenic mice on two different diets

    Directory of Open Access Journals (Sweden)

    Rønning Helle

    2005-10-01

    Full Text Available Abstract Background In man, elevated levels of plasma lipoprotein (a(Lp(a is a cardiovascular risk factor, and oxidized phospholipids are believed to play a role as modulators of inflammatory processes such as atherosclerosis. Polyamines are potent antioxidants and anti-inflammatory agents. It was therefore of interest to examine polyamines and their metabolism in LPA transgenic mice. Concentration of the polyamines putrescine, spermidine and spermine as well as the activity of peroxisomal polyamine oxidase and two other peroxisomal enzymes, acyl-CoA oxidase and catalase were measured. The mice were fed either a standard diet or a diet high in fat and cholesterol (HFHC. Some of the mice in each feeding group were in addition given aminoguanidine (AG, a specific inhibitor of diamine oxidase, which catalyses degradation of putrescine, and also inhibits non-enzymatic glycosylation of protein which is implicated in the aetiology of atherosclerosis in diabetic patients. Non-transgenic mice were used as controls. Results Intestinal peroxisomal polyamine oxidase activity was significantly higher in LPA transgenic mice than in the non-transgenic mice, while intestinal peroxisomal catalase activity was significantly lower. Hepatic β-oxidation increased in Lp(a transgenic mice fed the HFHC diet, but not in those on standard diet. Hepatic spermidine concentration was increased in all mice fed the HFHC diet compared to those fed a standard diet, while spermine concentration was decreased. With exception of the group fed only standard diet, transgenic mice showed a lower degree of hepatic steatosis than non-transgenic mice. AG had no significant effect on hepatic steatosis. Conclusion The present results indicate a connection between peroxisomal enzyme activity and the presence of the human LPA gene in the murine genome. The effect may be a result of changes in oxidative processes in lipid metabolism rather than resulting from a direct effect of the LPA

  4. Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine.

    Science.gov (United States)

    Xu, Huarong; Liu, Ran; He, Bosai; Bi, Cathy Wenchuan; Bi, Kaishun; Li, Qing

    2016-08-10

    Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography-tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50) and liver cancer patients (n = 50) were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer.

  5. Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine

    Directory of Open Access Journals (Sweden)

    Huarong Xu

    2016-08-01

    Full Text Available Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography—tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50 and liver cancer patients (n = 50 were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer.

  6. Depleted bulk heterojunction colloidal quantum dot photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, D.A.R. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); IBM Thomas J. Watson Research Center, Kitchawan Road, Yorktown Heights, NY, 10598 (United States); Debnath, Ratan; Kramer, Illan J.; Zhitomirsky, David; Levina, Larissa; Sargent, Edward H. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); Pattantyus-Abraham, Andras G. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); Quantum Solar Power Corporation, 1055 W. Hastings, Ste. 300, Vancouver, BC, V6E 2E9 (Canada); Etgar, Lioz; Graetzel, Michael [Laboratory for Photonics and Interfaces, Institute of Chemical Sciences and Engineering, School of Basic Sciences, Swiss Federal Institute of Technology, CH-1015 Lausanne (Switzerland)

    2011-07-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. Depleted Bulk Heterojunction Colloidal Quantum Dot Photovoltaics

    KAUST Repository

    Barkhouse, D. Aaron R.

    2011-05-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Effects of Riverbed Conductance on Stream Depletion

    Science.gov (United States)

    Lackey, G.; Neupauer, R. M.; Pitlick, J.

    2012-12-01

    In the western United States and other regions of the world where growing population and changing climates are threatening water supplies, accurate modeling of potential human impacts on water resources is becoming more important. Stream depletion, the reduction of surface water flow due to the extraction of groundwater from a hydraulically connected aquifer, is one of the more direct ways that development can alter water availability, degrade water quality and endanger aquatic habitats. These factors have made the accurate modeling of stream depletion an important step in the process of installing groundwater wells in regions that are susceptible to this phenomenon. Proper estimation of stream depletion requires appropriate parameterization of aquifer and streambed hydraulic properties. Although many studies have conducted numerical investigations to determine stream depletion at specific sites, they typically do not measure streambed hydraulic conductivity (Kr), but rather assume a representative value. In this work, we establish a hypothetical model aquifer that is 2000 m by 1600 m and has a meandering stream running through its center. The Kr of the model stream is varied from 1.0x10-9 m s-1 to 1.0x10-2 m s-1 in order to determine the sensitivity of the stream depletion calculations to this parameter. It was found that when Kr is in the lower part of this range, slight changes in K¬r lead to significant impacts on the calculated stream depletion values. We vary Kr along the stream channel according to naturally occurring patterns and demonstrate that alterations of the parameter over a few orders of magnitude can affect the estimated stream depletion caused by a well at a specified location. The numerical simulations show that the mean value of Kr and its spatial variability along the channel should be realistic to develop an accurate model of stream depletion.

  9. A theoretical model of atmospheric ozone depletion

    Science.gov (United States)

    Midya, S. K.; Jana, P. K.; Lahiri, T.

    1994-01-01

    A critical study on different ozone depletion and formation processes has been made and following important results are obtained: (i) From analysis it is shown that O3 concentration will decrease very minutely with time for normal atmosphere when [O], [O2] and UV-radiation remain constant. (ii) An empirical equation is established theoretically between the variation of ozone concentration and time. (iii) Special ozone depletion processes are responsible for the dramatic decrease of O3-concentration at Antarctica.

  10. Anatomy of Depleted Interplanetary Coronal Mass Ejections

    Science.gov (United States)

    Kocher, M.; Lepri, S. T.; Landi, E.; Zhao, L.; Manchester, W. B., IV

    2017-01-01

    We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE/SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C6+/C5+ and O7+/O6+ depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property of significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.

  11. ROLE OF POLYAMINES IN INHIBITION OF ETHYLENE BIOSYNTHESIS AND THEIR EFFECTS ON RICE ANTHER CULTURE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Iswari S. Dewi

    2016-10-01

    Full Text Available The polyamines such as putrescine, spermidine, and spermine were reported to increase green plant regeneration in rice anther culture. Low response of anther culture of rice sub-species indica may be improved with the addition of putrescine in the culture media. Four experiments were conducted to study the role of polyamines in inhibition of ethylene biosynthesis and their effects on rice anther culture development. Anthers of two subspecies of rice, indica (IR64, Krowal, Jatiluhur and japonica (Taipei 309 were cultured onto media supplemented with putrescine (N6P and without putrescine (N6. Youngpanicles containing the anthers at mid-to-late nucleate microspores were cold pretreated at 5 + 2°C and incubated in the dark for 8 days before the anthers were cultured. Resultsshowed that medium without putrescine produced an earlier senescence of indica rice anther than that of japonica. The addition of 10-3 M putrescine into the culture media inhibited ethylene biosynthesis as anther senescence delayed, increased the three polyamines contents, and decreased the ACC content as well as ACC oxydase activity in anther-derived calli. In the anther and anther-derived calli of subspecies indica, the totalpolyamines content was lower (10.14 nM g-1 anther and 8.48 nM g-1 calli than that of subspecies japonica (12.61 nM g-1 anther and 10.16 nM g-1 calli, whereas the ethylene production was higher (32.31 nM g-1 anther and 2.48 nM g-1 calli than the japonica (31.68 nM g-1 anther and 1.76 nM g-1 calli. This study suggests that application of 10-3 M putrescine in anther culture of rice subspecies indica improves androgenesis by inhibitingearly senescence of cultured anthers and enhancing embryo or callus formation from microspores.

  12. GABA shunt and polyamine degradation pathway on γ-aminobutyric acid accumulation in germinating fava bean (Vicia faba L.) under hypoxia.

    Science.gov (United States)

    Yang, Runqiang; Guo, Qianghui; Gu, Zhenxin

    2013-01-01

    GABA shunt and polyamine degradation pathway on γ-aminobutyric acid (GABA) accumulation in germinating fava bean under hypoxia was investigated. GABA content, GAD and DAO activity were significantly increased under hypoxia treatment. Glu and polyamine contents enhanced largely and thus supplied as sufficient substrates for GABA formation. In contrast, GABA content decreased, mainly in the embryo, after removing the hypoxia stress. DAO activity, Glu and polyamines contents decreased, while an increment of GAD activity was observed. This indicated that GAD activity can be not only regulated by hypoxia, but by the rapid growth of embryo after the recovery from hypoxia stress. When treated with AG, DAO activity was almost inhibited completely, and the GABA content decreased by 32.96% and 32.07% after treated for 3 and 5 days, respectively. Hence, it can be inferred that about 30% of GABA formed in germinating fava bean under hypoxia was supplied by polyamine degradation pathway.

  13. Polyamines as biomarkers for plant regeneration capacity: improvement of regeneration by modulation of polyamine metabolism in different genotypes of indica rice.

    Science.gov (United States)

    Shoeb, F; Yadav, J S.; Bajaj, S; Rajam, M V.

    2001-05-01

    The importance of cellular polyamine (PA) levels and the ratio of putrescine (Put) to spermidine (Spd) for plant regeneration ability via somatic embryogenesis in several commercially grown indica rice varieties is reported here. The genotypes namely NDR-624, IR-20, IR-36, BJ-1 (having Put:Spd ratio approximately 2.3) showed superior plant regeneration while KL, PB-1 and TN-1 (having Put:Spd ratio approximately 3.8) showed moderate plant regeneration ability. The genotypes namely HS, Bindli, DV-85, ACB-72, IR-64 and IR-72 (having Put:Spd ratio approximately 5.0) showed poor plant regeneration ability. In contrast KH-7 (Put:Spd ratio approximately 10.0) showed no response at all. Favorable modification of cellular PA titers and their Put:Spd ratio by the addition of exogenous PAs (Put, Spd) or their biosynthesis inhibitor, difluoromethylarginine (DFMA) led to the induction/promotion of plant regeneration in poorly responding genotypes. These results showed a close relationship between cellular PA levels and their Put:Spd ratio with in vitro morphogenetic capacity in indica rice and suggest that the cellular PAs and Put:Spd ratios are important determinants (biomarkers) of plant regeneration ability in indica rice, and the improvement/induction of plant regeneration in morphogenetically poor and recalcitrant species could be achieved by modulating PA metabolism.

  14. New Approach For Prediction Groundwater Depletion

    Science.gov (United States)

    Moustafa, Mahmoud

    2017-01-01

    Current approaches to quantify groundwater depletion involve water balance and satellite gravity. However, the water balance technique includes uncertain estimation of parameters such as evapotranspiration and runoff. The satellite method consumes time and effort. The work reported in this paper proposes using failure theory in a novel way to predict groundwater saturated thickness depletion. An important issue in the failure theory proposed is to determine the failure point (depletion case). The proposed technique uses depth of water as the net result of recharge/discharge processes in the aquifer to calculate remaining saturated thickness resulting from the applied pumping rates in an area to evaluate the groundwater depletion. Two parameters, the Weibull function and Bayes analysis were used to model and analyze collected data from 1962 to 2009. The proposed methodology was tested in a nonrenewable aquifer, with no recharge. Consequently, the continuous decline in water depth has been the main criterion used to estimate the depletion. The value of the proposed approach is to predict the probable effect of the current applied pumping rates on the saturated thickness based on the remaining saturated thickness data. The limitation of the suggested approach is that it assumes the applied management practices are constant during the prediction period. The study predicted that after 300 years there would be an 80% probability of the saturated aquifer which would be expected to be depleted. Lifetime or failure theory can give a simple alternative way to predict the remaining saturated thickness depletion with no time-consuming processes such as the sophisticated software required.

  15. 根发育过程中生长素、多胺和NO的关系%Relationships of Auxin, Polyamine and NO during Roots Development

    Institute of Scientific and Technical Information of China (English)

    张媛华; 张韶杰

    2012-01-01

    The relationships of auxin, polyamine and nitric oxide (NO) with root development were summarized, and the production mecha nisms of NO induced by auxin and polyamine was discussed.%综述了生长素、多胺和一氧化氮(NO)与根发育的关系,讨论了生长素和多胺诱导NO产生的机制.

  16. Measurement of camera image sensor depletion thickness with cosmic rays

    CERN Document Server

    Vandenbroucke, J; Bravo, S; Jensen, K; Karn, P; Meehan, M; Peacock, J; Plewa, M; Ruggles, T; Santander, M; Schultz, D; Simons, A L; Tosi, D

    2015-01-01

    Camera image sensors can be used to detect ionizing radiation in addition to optical photons. In particular, cosmic-ray muons are detected as long, straight tracks passing through multiple pixels. The distribution of track lengths can be related to the thickness of the active (depleted) region of the camera image sensor through the known angular distribution of muons at sea level. We use a sample of cosmic-ray muon tracks recorded by the Distributed Electronic Cosmic-ray Observatory to measure the thickness of the depletion region of the camera image sensor in a commercial smart phone, the HTC Wildfire S. The track length distribution prefers a cosmic-ray muon angular distribution over an isotropic distribution. Allowing either distribution, we measure the depletion thickness to be between 13.9~$\\mu$m and 27.7~$\\mu$m. The same method can be applied to additional models of image sensor. Once measured, the thickness can be used to convert track length to incident polar angle on a per-event basis. Combined with ...

  17. Sensing Conformational Changes in DNA upon Ligand Binding Using QCM-D. Polyamine Condensation and Rad51 Extension of DNA Layers

    KAUST Repository

    Sun, Lu

    2014-10-16

    © 2014 American Chemical Society. Biosensors, in which binding of ligands is detected through changes in the optical or electrochemical properties of a DNA layer confined to the sensor surface, are important tools for investigating DNA interactions. Here, we investigate if conformational changes induced in surface-attached DNA molecules upon ligand binding can be monitored by the quartz crystal microbalance with dissipation (QCM-D) technique. DNA duplexes containing 59-184 base pairs were formed on QCM-D crystals by stepwise assembly of synthetic oligonucleotides of designed base sequences. The DNA films were exposed to the cationic polyamines spermidine and spermine, known to condense DNA molecules in bulk experiments, or to the recombination protein Rad51, known to extend the DNA helix. The binding and dissociation of the ligands to the DNA films were monitored in real time by measurements of the shifts in resonance frequency (Δf) and in dissipation (ΔD). The QCM-D data were analyzed using a Voigt-based model for the viscoelastic properties of polymer films in order to evaluate how the ligands affect thickness and shear viscosity of the DNA layer. Binding of spermine shrinks all DNA layers and increases their viscosity in a reversible fashion, and so does spermidine, but to a smaller extent, in agreement with its lower positive charge. SPR was used to measure the amount of bound polyamines, and when combined with QCM-D, the data indicate that the layer condensation leads to a small release of water from the highly hydrated DNA films. The binding of Rad51 increases the effective layer thickness of a 59bp film, more than expected from the know 50% DNA helix extension. The combined results provide guidelines for a QCM-D biosensor based on ligand-induced structural changes in DNA films. The QCM-D approach provides high discrimination between ligands affecting the thickness and the structural properties of the DNA layer differently. The reversibility of the film

  18. Involvement of Polyamine Oxidase in Abscisic Acid induced Cytosolic Antioxidant Defense in Leaves of Maize

    Institute of Scientific and Technical Information of China (English)

    Beibei Xue; Aying Zhang; Mingyi Jiang

    2009-01-01

    Using pharmacological and biochemical approaches, the role of maize polyamine oxidase (MPAO) in abscisic acid (ABA)induced antioxidant defense in leaves of maize (Zea mays L.) plants was investigated. Exogenous ABA treatment enhanced the expression of the MPAO gene and the activities of apoplastic MPAO. Pretreatment with two different inhibitors for apoplastic MPAO partly reduced hydrogen peroxide (H2O2) accumulation induced by ABA and blocked the ABA-induced expression of the antioxidant genes superoxide dismutase 4 and cytosolic ascorbate peroxidase and the activities of the cytosolic antioxidant enzymes. Treatment with spermidine, the optimum substrate of MPAO, also induced the expression and the activities of the antioxidant enzymes, and the upregulation of the antioxidant enzymes was prevented by two inhibitors of MPAO and two scavengers of H2O2. These results suggest that MPAO contributes to ABA-induced cytosolic antioxidant defense through H2O2, a Spd catabolic product.

  19. Salicylic acid differently impacts ethylene and polyamine synthesis in the glycophyte Solanum lycopersicum and the wild-related halophyte Solanum chilense exposed to mild salt stress.

    Science.gov (United States)

    Gharbi, Emna; Martínez, Juan-Pablo; Benahmed, Hela; Fauconnier, Marie-Laure; Lutts, Stanley; Quinet, Muriel

    2016-10-01

    This study aimed to determine the effects of exogenous application of salicylic acid (SA) on the toxic effects of salt in relation to ethylene and polyamine synthesis, and to correlate these traits with the expression of genes involved in ethylene and polyamine metabolism in two tomato species differing in their sensitivity to salt stress, Solanum lycopersicum cv Ailsa Craig and its wild salt-resistant relative Solanum chilense. In S. chilense, treatment with 125 mM NaCl improved plant growth, increased production of ethylene, endogenous salicylic acid and spermine. The production was related to a modification of expression of genes involved in ethylene and polyamine metabolism. In contrast, salinity decreased plant growth in S. lycopersicum without affecting endogenous ethylene, salicylic or polyamine concentrations. Exogenous application of salicylic acid at 0.01 mM enhanced shoot growth in both species and affected ethylene and polyamine production in S. chilense. Concomitant application of NaCl and salicylic acid improved osmotic adjustment, thus suggesting that salt and SA may act in synergy on osmolyte synthesis. However, the beneficial impact of exogenous application of salicylic acid was mitigated by salt stress since NaCl impaired endogenous SA accumulation in the shoot and salicylic acid did not improve plant growth in salt-treated plants. Our results thus revealed that both species respond differently to salinity and that salicylic acid, ethylene and polyamine metabolisms are involved in salt resistance in S. chilense.

  20. Binding of the biogenic polyamines to deoxyribonucleic acids of varying base composition: base specificity and the associated energetics of the interaction.

    Directory of Open Access Journals (Sweden)

    Ayesha Kabir

    Full Text Available BACKGROUND: The thermodynamics of the base pair specificity of the binding of the polyamines spermine, spermidine, putrescine, and cadaverine with three genomic DNAs Clostridium perfringens, 27% GC, Escherichia coli, 50% GC and Micrococcus lysodeikticus, 72% GC have been studied using titration calorimetry and the data supplemented with melting studies, ethidium displacement and circular dichroism spectroscopy results. METHODOLOGY/PRINCIPAL FINDINGS: Isothermal titration calorimetry, differential scanning calorimetry, optical melting studies, ethidium displacement, circular dichroism spectroscopy are the various techniques employed to characterize the interaction of four polyamines, spermine, spermidine, putersine and cadaverine with the DNAs. Polyamines bound stronger with AT rich DNA compared to the GC rich DNA and the binding varied depending on the charge on the polyamine as spermine>spermidine >putrescine>cadaverine. Thermodynamics of the interaction revealed that the binding was entropy driven with small enthalpy contribution. The binding was influenced by salt concentration suggesting the contribution from electrostatic forces to the Gibbs energy of binding to be the dominant contributor. Each system studied exhibited enthalpy-entropy compensation. The negative heat capacity changes suggested a role for hydrophobic interactions which may arise due to the non polar interactions between DNA and polyamines. CONCLUSION/SIGNIFICANCE: From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies.

  1. Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549

    Institute of Scientific and Technical Information of China (English)

    HAN Yu; REN Yu-san; CAO Chun-yu; REN Dong-ming; ZHOU Yong-qin; WANG Yan-lin

    2009-01-01

    Background The critical roles of polyamines in cell growth and differentiation have made polyamine metabolic pathway a promising target for antitumor therapy. Recent studies have demonstrated in vitro that some antitumor polyamine analogues could be used as substrates and oxidized by purified recombinant human N1-acetylpolyamine oxidase (APAO, an enzyme that catabolizes natural polyamines), indicating a potential role of APAO in determining the sensitivity of cancer cells to specific antitumor analogues. This study evaluated, in vivo, the effect of APAO on cytotoxicity of antitumor polyamine analogue, N1-cyclopropylmethyI-N11-ethylnorspermine (CPENS) and its mechanism when highly expressed in human lung cancer line A549.Methods A clone with high expression of APAO was obtained by transfecting A549 lung cancer cell line with pcDNA3.1/APAO plasmid and selecting with quantitative realtime PCR and APAO activity assay. Cell proliferation was determined by MTT method and apoptosis related events were evaluated by DNA fragmentation, sub-G1/flow cytometric assay, western blotting (for cytochrome C and Bax) and colorimetric assay (for casapse-3 activity). Results A clone highly expressing APAO was obtained. High expression of APAO in A549 cells inhibited accumulation of CPENS, decreased their sensitivity to the toxicity of CPENS and prevented CPENS induced apoptosis. Conclusion These results indicate a new drug resisting, mechanism in the tumor cells. High expression of APAO can greatly decrease the sensitivity of tumor cells to the specific polyamine analogues by detoxitying those analogues and prevent analogue induced apoptosis.

  2. Regulation by the exogenous polyamine spermidine of Na,K-ATPase activity from the gills of the euryhaline swimming crab Callinectes danae (Brachyura, Portunidae).

    Science.gov (United States)

    Silva, E C C; Masui, D C; Furriel, R P M; Mantelatto, F L M; McNamara, J C; Barrabin, H; Leone, F A; Scofano, H M; Fontes, C F L

    2008-04-01

    Euryhaline crustaceans rarely hyporegulates and employ the driving force of the Na,K-ATPase, located at the basal surface of the gill epithelium, to maintain their hemolymph osmolality within a range compatible with cell function during hyper-regulation. Since polyamine levels increase during the adaptation of crustaceans to hyperosmotic media, we investigate the effect of exogenous polyamines on Na,K-ATPase activity in the posterior gills of Callinectes danae, a euryhaline swimming crab. Polyamine inhibition was dependent on cation concentration, charge and size in the following order: spermine>spermidine>putrescine. Spermidine affected K(0.5) values for Na(+) with minor alterations in K(0.5) values for K(+) and NH(4)(+), causing a decrease in maximal velocities under saturating Na(+), K(+) and NH(4)(+) concentrations. Phosphorylation measurements in the presence of 20 microM ATP revealed that the Na,K-ATPase possesses a high affinity site for this substrate. In the presence of 10 mM Na(+), both spermidine and spermine inhibited formation of the phosphoenzyme; however, in the presence of 100 mM Na(+), the addition of these polyamines allowed accumulation of the phosphoenzyme. The polyamines inhibited pumping activity, both by competing with Na(+) at the Na(+)-binding site, and by inhibiting enzyme dephosphorylation. These findings suggest that polyamine-induced inhibition of Na,K-ATPase activity may be physiologically relevant during migration to fully marine environments.

  3. Decrease in acrolein toxicity based on the decline of polyamine oxidases.

    Science.gov (United States)

    Uemura, Takeshi; Nakamura, Mizuho; Sakamoto, Akihiko; Suzuki, Takehiro; Dohmae, Naoshi; Terui, Yusuke; Tomitori, Hideyuki; Casero, Robert A; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-10-01

    We have shown recently that acrolein is strongly involved in cell damage during brain infarction and chronic renal failure. To study the mechanism of acrolein detoxification, we tried to isolate Neuro2a cells with reduced sensitivity to acrolein toxicity (Neuro2a-ATD cells). In one cell line, Neuro2a-ATD1, the level of glutathione (GSH) was increased. We recently isolated a second cell line, Neuro2a-ATD2, and found that acrolein-producing enzymes [polyamine oxidases (PAO); i.e. acetylpolyamine oxidase (AcPAO), and spermine oxidase (SMO)] are reduced in this cell line due to changes at the level of transcription. In the Neuro2a-ATD2 cells, the IC50 of acrolein increased from 4.2 to 6.8μM, and the levels of FosB and C/EBPβ - transcription factors involved in the transcription of AcPAO and SMO genes - were reduced. Transfection of siRNAs for FosB and C/EBPβ reduced the levels of AcPAO and SMO, respectively. In addition, the synthesis of FosB and AcPAO was also decreased by siRNA for C/EBPβ, because C/EBPβ is one of the transcription factors for the FosB gene. It was also found that transfection of siRNA for C/EBPβ decreased SMO promoter activity in Neuro2a cells but not in ATD2 cells confirming that a decrease in C/EBPβ is involved in the reduced SMO activity in Neuro2a-ATD2 cells. Furthermore, transfection of the cDNA for AcPAO or SMO into Neuro2a cells increased the toxicity of acrolein. These results suggest that acrolein is mainly produced from polyamines by PAO.

  4. Effect of end-of-day irradiations on polyamine accumulation in petal cultures of Araujia sericifera.

    Science.gov (United States)

    Moysset, Luisa; Trull, Olga; Santos, M. Asunción; Simón, Esther; Torné, Josep M

    2002-01-01

    We have studied photoperiodic control and the effect of phytochrome photoconversion at the end-of-day (EOD) on polyamine (PA) accumulation in petal explants of Araujia sericifera. Petals from immature flowers were cultured under long (LD) and short (SD) days. Light was provided by Gro-lux fluorescent lamps (90-100 &mgr;mol m-2 s-1). Red (R), far red (FR), red followed by far-red (R-FR) and far-red followed by red (FR-R) light treatments were applied daily at the end of the photoperiod. The free and bound putrescine (Put), spermidine (Spd) and spermine (Spm) fractions in petal explants were determined 40 days after the beginning of the culture. We also aimed to clarify the involvement of PA changes by using two inhibitors of PA biosynthesis: D-l-alpha-difluoromethylarginine (DFMA) and methylglyoxal bis(guanylhydrazone) (MGBG). We found PA accumulation to be under photoperiodic control, and the inhibitory effect of DFMA on this accumulation suggests that arginine decarboxylase (ADC) is the major pathway for Put biosynthesis. Polyamine levels were higher under LD, mainly as a result of the accumulation of free and bound Put. FR-EOD treatment, which dramatically reduced the R : FR ratio after LD, increased the accumulation of PA, mainly as free Put and free and bound Spd. Sequential R-FR and FR-R-EOD treatments strongly increased bound Spd. The concentration of MGBG used increased total PA accumulation, mainly as Put. However, all EOD light treatments dramatically reduced Put accumulation in the presence of MGBG. This may be due to a dual role of FR light in PA accumulation: (1) FR per se stimulates PA production, probably via ADC, and (2) in the presence of MGBG, FR inhibits Put accumulation, probably via ethylene production.

  5. Capillary electrophoresis of heparin and other glycosaminoglycans using a polyamine running electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Loegel, Thomas N.; Trombley, John D.; Taylor, Richard T. [Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 (United States); Danielson, Neil D., E-mail: danielnd@muohio.edu [Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 (United States)

    2012-11-13

    Highlights: Black-Right-Pointing-Pointer Ethylenediamine is likely acting as an ion-pairing agent. Black-Right-Pointing-Pointer Oversulfated chondroitin sulfate is last peak instead of first peak. Black-Right-Pointing-Pointer There is about a factor of five improved detectability with a 12.5 min analysis time. Black-Right-Pointing-Pointer Use of a 50 {mu}m ID capillary is possible. - Abstract: This study involves the use of polyamines as potential resolving agents for the capillary electrophoresis (CE) of glycosaminoglycans (GAGs), specifically heparin, dermatan sulfate, chondroitin sulfate, over-sulfated chondroitin sulfate (OSCS), and hyaluronan. All of the compounds can be separated from each other with the exception of chondroitin sulfate and hyaluronan. Using optimization software, the final run conditions are found to be 200 mM ethylenediamine and 45.5 mM phosphate as the electrolyte with -14 V applied across a 50 {mu}m ID Multiplication-Sign 24.5 cm fused silica capillary at 15 Degree-Sign C. The ion migration order, with OSCS as the last instead of the first peak, is in contrast to previous reports using either a high molarity TRIS or lithium phosphate run buffer with narrower bore capillaries. Total analysis time is 12. 5 min and the relative standard deviation of the heparin migration time is about 2.5% (n = 5). The interaction mechanism between selected polyamines and heparin is explored using conductivity measurements in addition to CE experiments to show that an ion-pairing mechanism is likely.

  6. Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism

    Institute of Scientific and Technical Information of China (English)

    Ji-fang WANG; Rui-bin SU; Ning WU; Bo XU; Xin-qiang LU; Yin LIU; Jin LI

    2005-01-01

    Aim: To assess the inhibitory effect of agmatine on tumor growth in vivo and tumor cell proliferation in vitro. Methods: The transplanted animal model,[3H]thymidine incorporation assay, 3- [4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazo lium assay, and lactate dehydrogenase (LDH) release assay were performed.Results: Agmatine, at doses of 5-40 mg/kg, suppressed the S180 sarcoma tumor growth dose-dependently in mice in vivo and the highest inhibitory ratio reached 31.3% in Kunming mice and 50.0% in Balb/c mice, respectively. Similar results were obtained in the transplanted B16 melanoma tumor model. Agmatine (1-1000 μmol/L) was able to attenuate the proliferation of cultured MCF-7 human breast cancer cells in vitro in a concentration-dependent manner and the highest inhibitory ratio reached 50.3% in the [3H]thymidine incorporation assay.Additionally, in the LDH release assay, spermine (20 μmol/L) and spermidine (20 μmol/L) increased the LDH release significantly, but agmatine (1-1000 μmol/L) did not, indicating that the inhibitory effect of agmatine on the proliferation of MCF was not related to cellular toxicity. In the [3H]thymidine incorporation assay,putrescine (12.5-100.0 μmol/L) could reverse the inhibitory effect of agmatine on the proliferation of MCF concentration-dependently, suggesting that the inhibitory effect of agmatine on the proliferation of MCF might be associated with a decreased level of the intracellular polyamines pool. Conclusion: Agmatine had significant inhibitory effect on transplanted tumor growth in vivo and proliferation of tumor cells in vitro, and the mechanism might be a result of inducing decrease of intracellular polyamine contents.

  7. Involvement of polyamines in adaptation of Potamogeton crispus L. to cadmium stress

    Energy Technology Data Exchange (ETDEWEB)

    Yang Haiyan, E-mail: haiyanyang_025@126.com [Institute of Plant Cell and Molecular Biology, College of Life Science, Nanjing Normal University, Nanjing, 210046 (China); Shi Guoxin, E-mail: gxshi@njnu.edu.cn [Institute of Plant Cell and Molecular Biology, College of Life Science, Nanjing Normal University, Nanjing, 210046 (China); Wang Hongxia; Xu Qinsong [Institute of Plant Cell and Molecular Biology, College of Life Science, Nanjing Normal University, Nanjing, 210046 (China)

    2010-11-01

    The effects of increasing concentrations of cadmium (Cd) on the ultrastructure, Cd accumulation, generation of O{sub 2}{center_dot}{sup -}, contents of ascorbate (AsA), reduced glutathione (GSH) and polyamines (PAs), as well as the activities of polyamine oxidase (PAO) (EC 1.5.3.3) and diamine oxidase (DAO) (EC 1.4.3.6) were investigated in the leaves of Potamogeton crispus. Cd exposure resulted in significant damage in chloroplasts and mitochondria, suggesting that Cd hastened the senescence of the tested plants. The accumulation of Cd was found to increase in a concentration-dependent manner, accompanied by increased production of O{sub 2}{center_dot}{sup -}. AsA content increased progressively up to 70 {mu}M Cd, followed by a decline at higher concentration. GSH content slightly increased up to 70 {mu}M Cd and then declined. In addition, Cd treatment increased the putrescine (Put) content, while decreasing spermidine (Spd) and spermine (Spm) contents, which reduced the ratio of free (Spd + Spm)/Put in the leaves. PS-conjugated PAs changed in the same pattern as free PAs, while PIS-bound PAs was different. PIS-bound Put content enhanced with the increase of Cd concentration up to 50 {mu}M and then decreased, and PIS-bound Spd and Spm contents decreased to a lesser extent. Moreover, the activities of PAO and DAO increased significantly with the increase of the Cd concentrations, reaching the peak values at 70 {mu}M Cd. Our results suggested that certain PAs and PAs forms could play a significant role in the adaptation mechanism of P. crispus under Cd stress.

  8. Study of copper(II) ternary complexes with phosphocreatine and some polyamines in aqueous solution.

    Science.gov (United States)

    Szyfman, Natalie W; Loureiro, Nina P; Tenório, Thaís; Mercê, Ana L R; Mangrich, Antônio Sálvio; Rey, Nicolás A; Felcman, Judith

    2011-12-01

    Ternary systems of Cu(II) with phosphocreatine (PCr) and the polyamines (PAs), ethylenediamine (en), 1,3-diaminopropane (tn), putrescine (Put), spermidine (Spd), and spermine (Spm), were investigated in aqueous solution through potentiometry, ultraviolet-visible, EPR and Raman spectroscopy. The binary complex CuPCr was also studied by Raman spectroscopy, and the calculation of the minimum stabilization energy was done assuming this molecule in aqueous solution. The stability constants of the CuPCrPA ternary complexes were determined by potentiometry (T=25°C, I=0.1 mol L(-1), KNO(3)). The stability order determined was CuPCrSpm>CuPCrSpd>CuPCren>CuPCrtn>CuPCrPut, the same order of the corresponding binary complexes of Cu(II) with these polyamines. The evaluation of intramolecular PA-PCr interactions in protonated and deprotonated species of ternary complexes was carried out using the equation Δlog K=log β(CuPCrPAHq+p)-(log β(CuPAHq)+log β(CuPCrHp)). All of the CuPCrPA ternary complexes have a square planar structure and are bonded to PCr through the nitrogen atom of the guanidine group and the oxygen atom of the phosphate group, and to the PAs through two nitrogen atoms of the amine groups. The structure of the complex CuPCrSpm is planar with distortion towards tetrahedral. Calculation of the minimum stabilization energy for the CuPCr and CuPCrenH complexes confirmed the proposed coordination mode. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. The EDGE--CALIFA Survey: Molecular Gas Depletion Time in Galaxy Centers

    Science.gov (United States)

    Utomo, Dyas; Blitz, Leo; Bolatto, Alberto D.; Wong, Tony H.; Ostriker, Eve C.; EDGE--CALIFA Collaboration

    2017-01-01

    We present the first results of the EDGE--CALIFA survey, combining the power of optical Integral Field Unit and millimeter-interferometric observations to study the variations of molecular gas depletion time in the centers of 86 galaxies. Our key findings are the following. (1) About 25% of our sample shows deviations from the Kennicutt-Schmidt relation, namely a shorter depletion time in the centers relative to the disks. If the galaxy centers undergo star formation cycles, then they spend 25% of their duty cycles in a burst-mode period. (2) Barred galaxies tend to have shorter depletion time in the centers, presumably due to the dynamical effects induced by bars. (3) Galaxies with shorter depletion time in the centers tend to have higher ratio of stellar to molecular gas gravity, because that ratio sets the gravitational pressure per unit molecular gas mass that must be balanced by the energy and momentum feedback from star formation to maintain thermal and dynamical equilibrium states. (4) Both depletion time and bar dynamics affect the gradient of gas-phase metallicities, where unbarred galaxies with shorter depletion time in the centers show the steepest gradient, presumably due to high star formation activities that inject more metals and lack of gas mixing because bars are not present. We discuss possible scenarios that may cause the variations of depletion time in the centers and their implications within the context of galaxy evolution.

  10. Ego depletion in visual perception: Ego-depleted viewers experience less ambiguous figure reversal.

    Science.gov (United States)

    Wimmer, Marina C; Stirk, Steven; Hancock, Peter J B

    2017-02-22

    This study examined the effects of ego depletion on ambiguous figure perception. Adults (N = 315) received an ego depletion task and were subsequently tested on their inhibitory control abilities that were indexed by the Stroop task (Experiment 1) and their ability to perceive both interpretations of ambiguous figures that was indexed by reversal (Experiment 2). Ego depletion had a very small effect on reducing inhibitory control (Cohen's d = .15) (Experiment 1). Ego-depleted participants had a tendency to take longer to respond in Stroop trials. In Experiment 2, ego depletion had small to medium effects on the experience of reversal. Ego-depleted viewers tended to take longer to reverse ambiguous figures (duration to first reversal) when naïve of the ambiguity and experienced less reversal both when naïve and informed of the ambiguity. Together, findings suggest that ego depletion has small effects on inhibitory control and small to medium effects on bottom-up and top-down perceptual processes. The depletion of cognitive resources can reduce our visual perceptual experience.

  11. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Science.gov (United States)

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion.

  12. Ozone depletion and chlorine loading potentials

    Science.gov (United States)

    Pyle, John A.; Wuebbles, Donald J.; Solomon, Susan; Zvenigorodsky, Sergei; Connell, Peter; Ko, Malcolm K. W.; Fisher, Donald A.; Stordal, Frode; Weisenstein, Debra

    1991-01-01

    The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere.

  13. Plasmonic nanoprobes for stimulated emission depletion microscopy

    CERN Document Server

    Cortes, Emiliano; Sinclair, Hugo G; Guldbrand, Stina; Peveler, William J; Davies, Timothy; Parrinello, Simona; Görlitz, Frederik; Dunsby, Chris; Neil, Mark A A; Sivan, Yonatan; Parkin, Ivan P; French, Paul M; Maier, Stefan A

    2016-01-01

    Plasmonic nanoparticles influence the absorption and emission processes of nearby emitters due to local enhancements of the illuminating radiation and the photonic density of states. Here, we use the plasmon resonance of metal nanoparticles in order to enhance the stimulated depletion of excited molecules for super-resolved microscopy. We demonstrate stimulated emission depletion (STED) microscopy with gold nanorods with a long axis of only 26 nm and a width of 8 nm that provide an enhancement of the resolution compared to fluorescent-only probes without plasmonic components irradiated with the same depletion power. These novel nanoparticle-assisted STED probes represent a ~2x10^3 reduction in probe volume compared to previously used nanoparticles and we demonstrate their application to the first plasmon-assisted STED cellular imaging. We also discuss their current limitations.

  14. Molten-Salt Depleted-Uranium Reactor

    CERN Document Server

    Dong, Bao-Guo; Gu, Ji-Yuan

    2015-01-01

    The supercritical, reactor core melting and nuclear fuel leaking accidents have troubled fission reactors for decades, and greatly limit their extensive applications. Now these troubles are still open. Here we first show a possible perfect reactor, Molten-Salt Depleted-Uranium Reactor which is no above accident trouble. We found this reactor could be realized in practical applications in terms of all of the scientific principle, principle of operation, technology, and engineering. Our results demonstrate how these reactors can possess and realize extraordinary excellent characteristics, no prompt critical, long-term safe and stable operation with negative feedback, closed uranium-plutonium cycle chain within the vessel, normal operation only with depleted-uranium, and depleted-uranium high burnup in reality, to realize with fission nuclear energy sufficiently satisfying humanity long-term energy resource needs, as well as thoroughly solve the challenges of nuclear criticality safety, uranium resource insuffic...

  15. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  16. Depletion of the nuclear Fermi sea

    CERN Document Server

    Rios, A; Dickhoff, W H

    2009-01-01

    The short-range and tensor components of the bare nucleon-nucleon interaction induce a sizeable depletion of low momenta in the ground state of a nuclear many-body system. The self-consistent Green's function method within the ladder approximation provides an \\textit{ab-initio} description of correlated nuclear systems that accounts properly for these effects. The momentum distribution predicted by this approach is analyzed in detail, with emphasis on the depletion of the lowest momentum state. The temperature, density, and nucleon asymmetry (isospin) dependence of the depletion of the Fermi sea is clarified. A connection is established between the momentum distribution and the time-ordered components of the self-energy, which allows for an improved interpretation of the results. The dependence on the underlying nucleon-nucleon interaction provides quantitative estimates of the importance of short-range and tensor correlations in nuclear systems.

  17. Sensitivity study of control rod depletion coefficients

    OpenAIRE

    Blomberg, Joel

    2015-01-01

    This report investigates the sensitivity of the control rod depletion coefficients, Sg, to different input parameters and how this affects the accumulated 10B depletion, β. Currently the coefficients are generated with PHOENIX4, but the geometries can be more accurately simulated in McScram. McScram is used to calculate Control Rod Worth, which in turn is used to calculate Nuclear End Of Life, and Sg cannot be generated in the current version of McScram. Therefore, it is also analyzed whether...

  18. Depletion methodology in the 3-D whole core transport code DeCART

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Seog; Cho, Jin Young; Zee, Sung Quun

    2005-02-01

    Three dimensional whole-core transport code DeCART has been developed to include a characteristics of the numerical reactor to replace partly the experiment. This code adopts the deterministic method in simulating the neutron behavior with the least assumption and approximation. This neutronic code is also coupled with the thermal hydraulic code CFD and the thermo mechanical code to simulate the combined effects. Depletion module has been implemented in DeCART code to predict the depleted composition in the fuel. The exponential matrix method of ORIGEN-2 has been used for the depletion calculation. The library of including decay constants, yield matrix and others has been used and greatly simplified for the calculation efficiency. This report summarizes the theoretical backgrounds and includes the verification of the depletion module in DeCART by performing the benchmark calculations.

  19. Measuring cohesion between macromolecular filaments, one pair at a time: Depletion-induced microtubule binding

    CERN Document Server

    Hilitski, Feodor; Cajamarca, Luis; Hagan, Michael F; Grason, Gregory M; Dogic, Zvonimir

    2014-01-01

    In presence of non-adsorbing polymers, colloidal particles experience a ubiquitous attractive interactions induced by the depletion mechanism. We measure the depletion interaction between a pair of microtubule filaments by a method that combines optical trapping, single molecule imaging and umbrella sampling. By quantifying the dependence of filament cohesion on both polymer concentration and solution ionic strength, we demonstrate that the minimal model of depletion based, on the Asakura-Oosawa theory, fails to describe the experimental data. By measuring the cohesion strength in two- and three- filament bundles we verify pairwise additivity of the depletion interaction for the specific experimental conditions. The described experimental technique can be used to measure pairwise interactions between various biological or synthetic filaments, thus complementing information extracted from bulk osmotic stress experiments.

  20. Excretion of polyamines in alfalfa and tobacco suspension-cultured cells and its possible role in maintenance of intracellular polyamine contents.

    Science.gov (United States)

    Cvikrová, Milena; Gemperlová, Lenka; Eder, Josef; Zazímalová, Eva

    2008-07-01

    Changes in polyamines (PAs) in cells and cultivation media of alfalfa (Medicago sativa L.) and tobacco bright yellow 2 (BY-2) (Nicotiana tabacum L.) cell suspension cultures were studied over their growth cycles. The total content of PAs (both free and conjugated forms) was nearly 10 times higher in alfalfa, with high level of free putrescine (Put) (in exponential growth phase it represented about 65-73% of the intracellular Put pool). In contrast, the high content of soluble Put conjugates was found in tobacco cells (in exponential phase about 70% of the intracellular Put). Marked differences occurred in the amount of PAs excreted into the cultivation medium: alfalfa cells excreted at the first day after inoculation 2117.0, 230.5, 29.0 and 88.0 nmol g(-1) of cell fresh weight (FW) of Put, spermidine (Spd), spermine (Spm) and cadaverine (Cad), respectively, while at the same time tobacco cells excreted only small amount of Put and Spd (12.7 and 2.4 nmol g(-1) FW, respectively). On day 1 the amounts of Put, Spd, Spm and Cad excreted by alfalfa cells represented 21, 38, 12 and 15% of the total pool (intra- plus extra-cellular contents) of Put, Spd, Spm and Cad, respectively. In the course of lag-phase and the beginning of exponential phase the relative contents of extracellular PAs continually decreased (with the exception of Cad). On day 10, the extracellular Put, Spd, Spm and Cad still represented 11.3, 10.9, 2.1 and 27% of their total pools. The extracellular PAs in tobacco cells represented from day 3 only 0.1% from their total pools. The possible role of PA excretion into the cultivation medium in maintenance of intracellular PA contents in the cells of the two cell culture systems, differing markedly in growth rate and PA metabolism is discussed.

  1. The application of polyamines by pressure or immersion as a tool to maintain functional properties in stored pomegranate arils.

    Science.gov (United States)

    Mirdehghan, Seyed Hossein; Rahemi, Majid; Serrano, María; Guillén, Fabian; Martínez-Romero, Domingo; Valero, Daniel

    2007-02-07

    Pomegranate fruits were treated with putrescine (Put) or spermidine (Spd) at 1 mM either by pressure infiltration or by immersion and then were stored at 2 degrees C for 60 days. Samples were taken biweekly and were further stored 3 days at 20 degrees C for shelf life study. The treatments were effective on maintaining the concentration of ascorbic acid, total phenolic compounds, and total anthocyanins in arils at higher levels than in control samples. In addition, the two ways of polyamine application increased the levels of total antioxidant activity (TAA) during storage, especially when polyamines were applied by pressure infiltration. Moreover, Spd showed the best results on increasing TAA through maintenance of total phenolic compounds.

  2. Hypusine modification for growth is the major function of spermidine in Saccharomyces cerevisiae polyamine auxotrophs grown in limiting spermidine.

    Science.gov (United States)

    Chattopadhyay, Manas K; Park, Myung Hee; Tabor, Herbert

    2008-05-06

    Spermidine and its derivative, hypusinated eIF5A, are essential for the growth of Saccharomyces cerevisiae. Very low concentrations of spermidine (10(-8) M) are sufficient for the growth of S. cerevisiae polyamine auxotrophs (spe1Delta, spe2Delta, and spe3Delta). Under these conditions, even though the growth rate is near normal, the internal concentration of spermidine is hypusinated eukaryotic initiation factor 5A (eIF5A) (1/20 of normal), even though there is no change in the amount of total (modified plus unmodified) eIF5A. It is striking that, as intracellular spermidine becomes limiting, an increasing portion of it (up to 54%) is used for the hypusine modification of eIF5A. These data indicate that hypusine modification of eIF5A is a most important function for spermidine in supporting the growth of S. cerevisiae polyamine auxotrophs.

  3. Depleted-Heterojunction Colloidal Quantum Dot Solar Cells

    KAUST Repository

    Pattantyus-Abraham, Andras G.

    2010-06-22

    Colloidal quantum dot (CQD) photovoltaics combine low-cost solution processability with quantum size-effect tunability to match absorption with the solar spectrum. Rapid recent advances in CQD photovoltaics have led to impressive 3.6% AM1.5 solar power conversion efficiencies. Two distinct device architectures and operating mechanisms have been advanced. The first-the Schottky device-was optimized and explained in terms of a depletion region driving electron-hole pair separation on the semiconductor side of a junction between an opaque low-work-function metal and a p-type CQD film. The second-the excitonic device-employed a CQD layer atop a transparent conductive oxide (TCO) and was explained in terms of diffusive exciton transport via energy transfer followed by exciton separation at the type-II heterointerface between the CQD film and the TCO. Here we fabricate CQD photovoltaic devices on TCOs and show that our devices rely on the establishment of a depletion region for field-driven charge transport and separation, and that they also exploit the large bandgap of the TCO to improve rectification and block undesired hole extraction. The resultant depletedheterojunction solar cells provide a 5.1% AM1.5 power conversion efficiency. The devices employ infrared-bandgap size-effect-tuned PbS CQDs, enabling broadband harvesting of the solar spectrum. We report the highest opencircuit voltages observed in solid-state CQD solar cells to date, as well as fill factors approaching 60%, through the combination of efficient hole blocking (heterojunction) and very small minority carrier density (depletion) in the large-bandgap moiety. © 2010 American Chemical Society.

  4. Effects of aluminum on growth, polyamine metabolism, and inorganic ions in suspension cultures of red spruce (Picea rubens)

    Science.gov (United States)

    Rakesh Minocha; Walter C. Shortle; Daniel J. Jr. Coughin; Subhash C. Minocha

    1996-01-01

    The influence of age of red spruce (Picea rubens Sarg.) cell suspensions on aluminum (Al) effects was studied by adding AICI3 (0.2, 0.5, and 1.0 mM) to the media on each day of a 7-day culture period and analyzing for changes in total cell mass, polyamines, arginine decarboxylase activity, and inorganic ions after 24 h of...

  5. Rhizobacterial Strain Bacillus megaterium BOFC15 Induces Cellular Polyamine Changes that Improve Plant Growth and Drought Resistance

    OpenAIRE

    Cheng Zhou; Zhongyou Ma; Lin Zhu; Xin Xiao; Yue Xie; Jian Zhu; Jianfei Wang

    2016-01-01

    Plant-growth-promoting rhizobacteria can improve plant growth, development, and stress adaptation. However, the underlying mechanisms are still largely unclear. We investigated the effects of Bacillus megaterium BOFC15 on Arabidopsis plants. BOFC15 produced and secreted spermidine (Spd), a type of polyamine (PA) that plays an important role in plant growth. Moreover, BOFC15 induced changes in the cellular PAs of plants that promoted an increase of free Spd and spermine levels. However, these ...

  6. A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA*

    Science.gov (United States)

    Yordanova, Martina M.; Wu, Cheng; Andreev, Dmitry E.; Sachs, Matthew S.; Atkins, John F.

    2015-01-01

    The protein antizyme is a negative regulator of cellular polyamine concentrations from yeast to mammals. Synthesis of functional antizyme requires programmed +1 ribosomal frameshifting at the 3′ end of the first of two partially overlapping ORFs. The frameshift is the sensor and effector in an autoregulatory circuit. Except for Saccharomyces cerevisiae antizyme mRNA, the frameshift site alone only supports low levels of frameshifting. The high levels usually observed depend on the presence of cis-acting stimulatory elements located 5′ and 3′ of the frameshift site. Antizyme genes from different evolutionary branches have evolved different stimulatory elements. Prior and new multiple alignments of fungal antizyme mRNA sequences from the Agaricomycetes class of Basidiomycota show a distinct pattern of conservation 5′ of the frameshift site consistent with a function at the amino acid level. As shown here when tested in Schizosaccharomyces pombe and mammalian HEK293T cells, the 5′ part of this conserved sequence acts at the nascent peptide level to stimulate the frameshifting, without involving stalling detectable by toe-printing. However, the peptide is only part of the signal. The 3′ part of the stimulator functions largely independently and acts at least mostly at the nucleotide level. When polyamine levels were varied, the stimulatory effect was seen to be especially responsive in the endogenous polyamine concentration range, and this effect may be more general. A conserved RNA secondary structure 3′ of the frameshift site has weaker stimulatory and polyamine sensitizing effects on frameshifting. PMID:25998126

  7. A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA.

    Science.gov (United States)

    Yordanova, Martina M; Wu, Cheng; Andreev, Dmitry E; Sachs, Matthew S; Atkins, John F

    2015-07-17

    The protein antizyme is a negative regulator of cellular polyamine concentrations from yeast to mammals. Synthesis of functional antizyme requires programmed +1 ribosomal frameshifting at the 3' end of the first of two partially overlapping ORFs. The frameshift is the sensor and effector in an autoregulatory circuit. Except for Saccharomyces cerevisiae antizyme mRNA, the frameshift site alone only supports low levels of frameshifting. The high levels usually observed depend on the presence of cis-acting stimulatory elements located 5' and 3' of the frameshift site. Antizyme genes from different evolutionary branches have evolved different stimulatory elements. Prior and new multiple alignments of fungal antizyme mRNA sequences from the Agaricomycetes class of Basidiomycota show a distinct pattern of conservation 5' of the frameshift site consistent with a function at the amino acid level. As shown here when tested in Schizosaccharomyces pombe and mammalian HEK293T cells, the 5' part of this conserved sequence acts at the nascent peptide level to stimulate the frameshifting, without involving stalling detectable by toe-printing. However, the peptide is only part of the signal. The 3' part of the stimulator functions largely independently and acts at least mostly at the nucleotide level. When polyamine levels were varied, the stimulatory effect was seen to be especially responsive in the endogenous polyamine concentration range, and this effect may be more general. A conserved RNA secondary structure 3' of the frameshift site has weaker stimulatory and polyamine sensitizing effects on frameshifting. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Mathematical modelling of polyamine metabolism in bloodstream-form Trypanosoma brucei: an application to drug target identification.

    Directory of Open Access Journals (Sweden)

    Xu Gu

    Full Text Available We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT and ornithine production (OrnPt have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.

  9. Effect of fluazifop-p-butyl treatment on pigments and polyamines level within tissues of non-target maize plants.

    Science.gov (United States)

    Horbowicz, Marcin; Sempruch, Cezary; Kosson, Ryszard; Koczkodaj, Danuta; Walas, Dajana

    2013-09-01

    Fluazifop-p-butyl (FL) is one of the most popular graminicides from arylophenoxypropionate group. These herbicides act as inhibitors of acetyl-CoA carboxylase (ACCase) that catalyzes the formation of malonyl-CoA during metabolism of lipids and/or of some secondary compounds. On the other hand arylopropionates and cyclohexanediones cause phytotoxic effects by stimulating free-radicals generation and causing oxidative stress in susceptible plants. However, the importance of disturbances in plant pigments and polyamines accumulation for this effect is not clear. The aim of this work is to quantify the phytotoxicity of FL to non target maize plant and to explain how photosynthetic pigments, anthocyanins (ANC) and polyamines participate in this interaction. Obtained results showed reduction of chlorophyll a and b, but only in case of the highest herbicide dose. Lower FL concentrations caused increase of the photosynthetic pigments, or were not effective. A similar effect was stated for putrescine, while spermidine was reduced within epicotyl of leaf tissues. In case of 2-phenylethylamine (PEA), there was observed a lack of significant changes within leaves and an increase in epicotyl under the middle and the highest dose of the herbicide. Moreover, FL induced ANC accumulation in epicotyls of maize seedlings. The activity of such key enzymes of polyamine biosynthesis as: ornithine decarboxylase (ODC) and lysine decarboxylase (LDC), increased in leaves treated with herbicide at the lowest concentration and decreased under the highest. However, in case of epicotyls the decreasing tendency was observed with the exception of ODC under the highest FL dose. The activity of tyrosine decarboxylase (TyDC) was importantly elevated only within epicotyls under the lower FL concentrations. It was concluded that FL inhibits maize growth, and the intensity of the effect is positively correlated with the herbicide concentration. The phenomenon was related to changes in content of

  10. Chromium stress mitigation by polyamine-brassinosteroid application involves phytohormonal and physiological strategies in Raphanus sativus L.

    Directory of Open Access Journals (Sweden)

    Sikander Pal Choudhary

    Full Text Available Brassinosteroids (BRs and polyamines (PAs are well-established growth regulators playing key roles in stress management among plants. In the present study, we evaluated the effects of epibrassinolide (EBL, an active BR and spermidine (Spd, an active PA on the tolerance of radish to oxidative stress induced by Cr (VI metal. Our investigation aimed to study the impacts of EBL (10(-9 M and/or Spd (1 mM on the biochemical and physiological responses of radish (Raphanus sativus L. under Cr-stress. Applications of EBL and/or Spd were found to improve growth of Cr-stressed seedlings in terms of root length, shoot length and fresh weight. Our data also indicated that applications of EBL and Spd have significant impacts, particularly when applied together, on the endogenous titers of PAs, free and bound forms of IAA and ABA in seedlings treated with Cr-stress. Additionally, co-applications of EBL and Spd modulated more remarkably the titers of antioxidants (glutathione, ascorbic acid, proline, glycine betaine and total phenol and activities of antioxidant enzymes (guaicol peroxidase, catalase, superoxide dismutase and glutathione reductase in Cr-stressed plants than their individual applications. Attenuation of Cr-stress by EBL and/or Spd (more efficient with EBL and Spd combination was also supported by enhanced values of stress indices, such as phytochelatins, photosynthetic pigments and total soluble sugars, and reduction in malondialdehyde and H(2O(2 levels in Cr-treated seedlings. Diminution of ROS production and enhanced ROS scavenging capacities were also noted for EBL and/or Spd under Cr-stress. However, no significant reduction in Cr uptake was observed for co-application of EBL and Spd when compared to their individual treatments in Cr-stressed seedlings. Taken together, our results demonstrate that co-applications of EBL and Spd are more effective than their independent treatments in lowering the Cr-induced oxidative stress in radish, leading

  11. Chromium stress mitigation by polyamine-brassinosteroid application involves phytohormonal and physiological strategies in Raphanus sativus L.

    Science.gov (United States)

    Choudhary, Sikander Pal; Kanwar, Mukesh; Bhardwaj, Renu; Yu, Jing-Quan; Tran, Lam-Son Phan

    2012-01-01

    Brassinosteroids (BRs) and polyamines (PAs) are well-established growth regulators playing key roles in stress management among plants. In the present study, we evaluated the effects of epibrassinolide (EBL, an active BR) and spermidine (Spd, an active PA) on the tolerance of radish to oxidative stress induced by Cr (VI) metal. Our investigation aimed to study the impacts of EBL (10(-9) M) and/or Spd (1 mM) on the biochemical and physiological responses of radish (Raphanus sativus L.) under Cr-stress. Applications of EBL and/or Spd were found to improve growth of Cr-stressed seedlings in terms of root length, shoot length and fresh weight. Our data also indicated that applications of EBL and Spd have significant impacts, particularly when applied together, on the endogenous titers of PAs, free and bound forms of IAA and ABA in seedlings treated with Cr-stress. Additionally, co-applications of EBL and Spd modulated more remarkably the titers of antioxidants (glutathione, ascorbic acid, proline, glycine betaine and total phenol) and activities of antioxidant enzymes (guaicol peroxidase, catalase, superoxide dismutase and glutathione reductase) in Cr-stressed plants than their individual applications. Attenuation of Cr-stress by EBL and/or Spd (more efficient with EBL and Spd combination) was also supported by enhanced values of stress indices, such as phytochelatins, photosynthetic pigments and total soluble sugars, and reduction in malondialdehyde and H(2)O(2) levels in Cr-treated seedlings. Diminution of ROS production and enhanced ROS scavenging capacities were also noted for EBL and/or Spd under Cr-stress. However, no significant reduction in Cr uptake was observed for co-application of EBL and Spd when compared to their individual treatments in Cr-stressed seedlings. Taken together, our results demonstrate that co-applications of EBL and Spd are more effective than their independent treatments in lowering the Cr-induced oxidative stress in radish, leading to

  12. Contrasts between Antarctic and Arctic ozone depletion.

    Science.gov (United States)

    Solomon, Susan; Portmann, Robert W; Thompson, David W J

    2007-01-09

    This work surveys the depth and character of ozone depletion in the Antarctic and Arctic using available long balloon-borne and ground-based records that cover multiple decades from ground-based sites. Such data reveal changes in the range of ozone values including the extremes observed as polar air passes over the stations. Antarctic ozone observations reveal widespread and massive local depletion in the heart of the ozone "hole" region near 18 km, frequently exceeding 90%. Although some ozone losses are apparent in the Arctic during particular years, the depth of the ozone losses in the Arctic are considerably smaller, and their occurrence is far less frequent. Many Antarctic total integrated column ozone observations in spring since approximately the 1980s show values considerably below those ever observed in earlier decades. For the Arctic, there is evidence of some spring season depletion of total ozone at particular stations, but the changes are much less pronounced compared with the range of past data. Thus, the observations demonstrate that the widespread and deep ozone depletion that characterizes the Antarctic ozone hole is a unique feature on the planet.

  13. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  14. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  15. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    Science.gov (United States)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

  16. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, S.J.; Adriaanse, M.A.; Vet, de E.W.M.L.; Fennis, B.M.; Ridder, de D.T.D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  17. Inhibition of polyamine biosynthesis in Crithidia fasciculata by D,L-alpha-difluoromethylornithine and D,L-alpha-difluoromethylarginine.

    Science.gov (United States)

    Hunter, K J; Strobos, C A; Fairlamb, A H

    1991-05-01

    Using Crithidia fasciculata as a model organism for Trypanosoma cruzi, we have examined the effects of D,L-alpha-difluoromethylornithine (DFMO) and D,L-alpha-difluoromethylarginine (DFMA) on growth and polyamine synthesis. In a defined, polyamine-free medium growth was markedly inhibited by DFMO (94% at 50 mM; IC50 = 37 mM) and to a lesser extent by DFMA (65% at 50 mM). Addition of putrescine, but not agmatine, reverses inhibition of growth, suggesting that the site of inhibition is ornithine decarboxylase (ODC). Consistent with this conclusion, DFMO or DFMA results in a complete loss of putrescine and significant reductions in intracellular spermidine, glutathionylspermidine and N1,N8-bis(glutathionyl)spermidine (trypanothione). In addition, significant concentrations of DFMO (0.8 mM) were present in DFMA-treated cells. However, in contrast to other organisms, conversion of DFMA to DFMO is probably not catalysed by arginase. Substantial ornithine decarboxylase activity (63.1 pmol min-1 mg-1; ODC) was observed in control cells, sufficient to account for polyamine synthesis during growth. In addition, a trace arginine decarboxylase (ADC) activity (1.19 pmol min-1 mg-1) was found. Evidence is presented showing that the apparent ADC activity is actually due to the concerted action of arginase (1.5 nmol min-1 mg-1) and ODC. Thus DFMA appears to inhibit growth of C. fasciculata via conversion to DFMO and subsequent inhibition of ODC.

  18. Accumulation of wound-inducible ACC synthase transcript in tomato fruit is inhibited by salicylic acid and polyamines.

    Science.gov (United States)

    Li, N; Parsons, B L; Liu, D R; Mattoo, A K

    1992-02-01

    Regulation of wound-inducible 1-aminocyclopropane-1-carboxylic acid (ACC) synthase expression was studied in tomato fruit (Lycopersicon esculentum cv. Pik-Red). A 70 base oligonucleotide probe homologous to published ACC synthase cDNA sequences was successfully used to identify and analyze regulation of a wound-inducible transcript. The 1.8 kb ACC synthase transcript increased upon wounding the fruit as well as during fruit ripening. Salicylic acid, an inhibitor of wound-responsive genes in tomato, inhibited the wound-induced accumulation of the ACC synthase transcript. Further, polyamines (putrescine, spermidine and spermine) that have anti-senescence properties and have been shown to inhibit the development of ACC synthase activity, inhibited the accumulation of the wound-inducible ACC synthase transcript. The inhibition by spermine was greater than that caused by putrescine or spermidine. The transcript level of a wound-repressible glycine-rich protein gene and that of the constitutively expressed rRNA were not affected as markedly by either salicylic acid or polyamines. These data suggest that salicylic acid and polyamines may specifically regulate ethylene biosynthesis at the level of ACC synthase transcript accumulation.

  19. EFFECT OF EXOGENOUS POLYAMINE DIETHYLENETRIAMINE ON OXIDATIVE CHANGES AND PHOTOSYNTHESIS IN AS-TREATED MAIZE PLANTS (Zea mays L.

    Directory of Open Access Journals (Sweden)

    N STOEVA

    2006-05-01

    Full Text Available The antioxidant effect of the exogenous polyamine Diethylentriamine (DETA on the oxidative changes in young maize plants treated with different As concentrations was studied. The plants were grown in a climatic box in a Hogland-Arnon nutrient solution. Arsenic was applied as Na3As04 in concentrations 0, 2 and 5 mg dm-3 (pH 5.5. The polyamine DETA (concentration 10-4 М was added to the nutrient environment of some of the plants 24 hours prior to the As treatment. Five days later the lipid peroxidation level, the peroxidase activity, the growth and leaf gasexchange, and the protein and plastid pigments content were studied. The physiological analyses proved that DETA had positive effect on the As-treated maize plants by increasing the leaf gas-exchange, the plastid pigments content and soluble protein. The exogenous polyamine DETA, applied 24 hours prior to the As treatment, decreased considerably the lipid peroxidation level and the peroxidase itself in maize plants. DETA had protective effect on the As-induced oxidative stress, but in order to clarify its role as an antioxidant, more detailed and profound studies should be made.

  20. Accelerated Hydrolysis of p-Nitrophenyl Picolinate Catalyzed by Metallomicelle Made from a Novel Macrocyclic Polyamine Copper(Ⅱ) Complex

    Institute of Scientific and Technical Information of China (English)

    KOU,Xing-Ming; ZHAO,Guo-Po; HUANG,Zhong; TIAN,Yu-Hua; MENG,Xiang-Guang; ZENG Xian-Cheng

    2007-01-01

    A copper(Ⅱ) complex 1 of a novel macrocyclic polyamine ligand with hydroxylethyl pendant groups, 4,ll-bis(hydroxylethyl)-5,7,7,12,14,14-hexamethyl-l,4,8,11-tetraazacyclotetradecane (L) has been synthesized and characterized. Rate enhancement for hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by 1 was studied kinetically under Brij35 micellar condition. For comparision, the catalytic activity of corresponding copper(Ⅱ) complex 2 of non-substituted macrocyclic polyamine ligand, 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraaza-cyclote-tradecane (L1) toward the hydrolysis of PNPP was also investigated. The results indicate that the macrocyclic polyamine copper(Ⅱ) complex 1 effectively catalyzed the hydrolysis of PNPP, and the pendant ligand hydroxyl group or deprotonated pendant ligand hydroxyl group can act as catalytically active species in the reaction. A ternary complex kinetic model involving metal ion, ligand and substrate has been proposed, and the results confirmed the reasonability of such kinetic model.

  1. Polyamine and nitric oxide crosstalk: Antagonistic effects on cadmium toxicity in mung bean plants through upregulating the metal detoxification, antioxidant defense and methylglyoxal detoxification systems.

    Science.gov (United States)

    Nahar, Kamrun; Hasanuzzaman, Mirza; Alam, Md Mahabub; Rahman, Anisur; Suzuki, Toshisada; Fujita, Masayuki

    2016-04-01

    Cadmium (Cd) contamination is a serious agricultural and environmental hazard. The study investigates cross-protection roles of putrescine (Put, 0.2 mM) and nitric oxide (sodium nitroprusside; SNP, 1 mM) in conferring Cd (CdCl2, 1.5 mM) tolerance in mung bean (Vigna radiata L. cv. BARI Mung-2) seedlings. Cadmium stress increased root and shoot Cd content, reduced growth, destroyed chlorophyll (chl), modulated proline (Pro) and reduced leaf relative water content (RWC), increased oxidative damage [lipid peroxidation, H2O2 content, O2(∙-) generation rate, lipoxygenase (LOX) activity], methylglyoxal (MG) toxicity. Put and/or SNP reduced Cd uptake, increasd phytochelatin (PC) content, reduced oxidative damage enhancing non-enzymatic antioxidants (AsA and GSH) and activities of enzymes [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST), and glutathione peroxidase (GPX)]. Exogenous Put and/or SNP modulated endogenous polyamines, PAs (putrescine, Put; spermidine, Spd; spermine, Spm), and NO; improved glyoxalase system in detoxifying MG and improved physiology and growth where combined application showed better effects which designates possible crosstalk between NO and PAs to confer Cd-toxicity tolerance.

  2. Epibrassinolide induces changes in indole-3-acetic acid, abscisic acid and polyamine concentrations and enhances antioxidant potential of radish seedlings under copper stress.

    Science.gov (United States)

    Choudhary, Sikander Pal; Bhardwaj, Renu; Gupta, Bishan Datt; Dutt, Prabhu; Gupta, Rajinder Kumar; Biondi, Stefania; Kanwar, Mukesh

    2010-11-01

    In the present study, the effects of epibrassinolide (EBL) on indole-3-acetic acid (IAA), abscisic acid (ABA) and polyamine (PA) tissue concentrations and antioxidant potential of 7-day-old Raphanus sativus L. cv. 'Pusa chetki' seedlings grown under Cu stress were investigated. EBL treatment alone or in combination with Cu enhanced free and bound IAA titers when compared with the metal alone. Modest increases in free and bound ABA contents were observed for EBL treatment alone. However, the combination of EBL with Cu caused major increases in both forms of ABA, over Cu alone. Among the PAs analyzed, only putrescine and cadaverine concentrations were enhanced by EBL treatment alone. By contrast, a significant decline in putrescine and spermine contents was found in seedlings treated with EBL plus Cu. EBL treatments alone or in combination with Cu enhanced activities of guaiacol peroxidase (EC1.11.1.7), catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and glutathione reductase (EC 1.6.4.2) and protein contents in comparison with metal and control treatments. A major decrease in malondialdehyde content was also recorded for EBL treatments with or without Cu. An increase in phytochelatin content was also observed in seedlings treated with EBL alone or in combination with Cu. Major improvement in radical scavenging activities, as attested by the antioxidant activity assay using DPPH (1,1-diphenylpicrylhydrazyl), and elevated deoxyribose and reducing powers, along with increased contents of ascorbic acid, total phenols and proline, also suggest a major influence of EBL application in mitigating copper-induced oxidative stress in radish seedlings. Copyright © Physiologia Plantarum 2010.

  3. Neutron-activation revisited: the depletion and depletion-activation models.

    Science.gov (United States)

    Abdel-Rahman, Wamied; Podgorsak, Ervin B

    2005-02-01

    The growth of a radioactive daughter in neutron activation is commonly described with the saturation model that ignores the consumption of parent nuclei during the radio-activation process. This approach is not valid when radioactive sources with high specific activities are produced or when the particle fluence rates used are very high. Assuming a constant neutron fluence rate throughout the activation target, a neutron-activation model that accounts for the depletion in parent nuclei is introduced. This depletion model is governed by relationships similar to those describing the parent-daughter-granddaughter decay series, and, in contrast to the saturation model, correctly predicts the practical limit of the daughter specific activity, irrespective of the particle fluence rate. Also introduced is a neutron-activation model that in addition to parent depletion accounts for the neutron activation of daughter nuclei in situations where the cross section for this effect is high. The model is referred to as the depletion-activation model and it provides the most realistic description for the daughter specific activity in neutron activation. Three specific neutron activation examples of interest to medical physics are presented: activation of molybdenum-98 into molybdenum-99 described by the saturation model; activation of cobalt-59 into cobalt-60 described by the depletion model; and activation of iridium-191 into iridium-192 described by the depletion-activation model.

  4. Replacements For Ozone-Depleting Foaming Agents

    Science.gov (United States)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  5. Assessment of Preferred Depleted Uranium Disposal Forms

    Energy Technology Data Exchange (ETDEWEB)

    Croff, A.G.; Hightower, J.R.; Lee, D.W.; Michaels, G.E.; Ranek, N.L.; Trabalka, J.R.

    2000-06-01

    The Department of Energy (DOE) is in the process of converting about 700,000 metric tons (MT) of depleted uranium hexafluoride (DUF6) containing 475,000 MT of depleted uranium (DU) to a stable form more suitable for long-term storage or disposal. Potential conversion forms include the tetrafluoride (DUF4), oxide (DUO2 or DU3O8), or metal. If worthwhile beneficial uses cannot be found for the DU product form, it will be sent to an appropriate site for disposal. The DU products are considered to be low-level waste (LLW) under both DOE orders and Nuclear Regulatory Commission (NRC) regulations. The objective of this study was to assess the acceptability of the potential DU conversion products at potential LLW disposal sites to provide a basis for DOE decisions on the preferred DU product form and a path forward that will ensure reliable and efficient disposal.

  6. L-Tryptophan depletion bioreactor, a possible cancer therapy

    Directory of Open Access Journals (Sweden)

    Rolf Bambauer

    2015-04-01

    Full Text Available The cancer therapeutic strategies knownto date are not adequate for all cancer patients. Most of them are followed by a high rate of side effects and complications. The L-tryptophan depletion bioreactor is described as a possible new method of cancer therapy. L-tryptophan is an essential amino acid which has been recognized as an important cancer nutrient and its removal can lead to destruction of the tumour. Normal human cells or tumor cells cannot synthesize L-tryptophan and therefore tumor resistance is unlikely to develop. L-tryptophan is also a constituent for different bio-molecules such as Serotonin, Melatonin, and is needed for other synthesis processes in the cell growth. L-tryptophan degrading enzymes with 3 iso-enzymes called tryptophan side chain oxydase (TSO I, II, III were isolated. The 3 iso-enzymes can be differentiated by tryptic digestion. They have different molecular weights with different effectivenesses. All the TSO enzymes have heme that can catalyze essentially similar reactions involving L-tryptophan as a substrate. The most effective TSO is the type TSO III. A column which contained TSO as a bioreactor was integrated in a plasmapheresis unit and tested it in different animals. In sheep and rabbits L-tryptophan depletion in plasma was shown at 95% and 100% rates respectively by a single pass through the bioreactor. The results in immune supprimized rats with tumors were impressive, too. In 20 different tumor cell lines there were different efficacies. Brest cancer and medulloblastoma showed the greatest efficacy of L-tryptophan degrading. The gene technology of TSO production from Pseudomonas is associated with formation of endotoxins. This disadvantage can be prevented by different washing procedures or by using fungal sources for the TSO production. TSO III is developed to treat cancer diseases successfully, and has low side effects. A combination of L-tryptophan depletion with all available cancer therapies is

  7. Ecological and corrosion behavior of depleted uranium

    Directory of Open Access Journals (Sweden)

    Stojanović Mirjana D.

    2015-01-01

    Full Text Available Environmental pollution with radionuclides, particularly uranium and its decay products is a serious global problem. The current scientific studies estimated that the contamination originating from TENORM, caused by nuclear and non-nuclear technologies, has significantly increased natural level of radioactivity in the last thirty years. During the last decades all the more were talking about the "new pollutant" - depleted uranium (DU, which has been used in anti-tank penetrators because of its high density, penetration and pyrophoric properties. It is estimated that during the Gulf War, the war in Bosnia and Yugoslavia and during the invasion of Iraq, 1.4 million missiles with depleted uranium was fired. During the NATO aggression against the ex Yugoslavia in 1999., 112 locations in Kosovo and Metohija, 12 locations in southern Serbia and two locations in Montenegro were bombed. On this occasion, approximately 10 tons of depleted uranium were entered into the environment, mainly on land, where the degree of contamination ranged from 200 Bq / kg to 235 000 Bq/kg, which is up to 1000 times higher than the natural level. Fourteen years ago there was very little information about the behavior of ecological systems damaged by DU penetrators fired. Today, unfortunately, we are increasingly faced with the ―invisible threat" of depleted uranium, which has a strong radioactive and hemotoxic impact on human health. Present paper provides a detailed overview of the current understanding of corrosion and corrosion behavior of DU and environmental factors that control corrosion, together with indicators of environmental impact in order to highlight areas that need further attention in developing remediation programs.

  8. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  9. Polyamine is a critical determinant of Pseudomonas chlororaphis O6 for GacS-dependent bacterial cell growth and biocontrol capacity.

    Science.gov (United States)

    Park, Ju Yeon; Kang, Beom Ryong; Ryu, Choong-Min; Anderson, Anne J; Kim, Young Cheol

    2017-09-01

    The Gac/Rsm network regulates at the transcriptional level many beneficial traits in biocontrol-active pseudomonads. In this study, we used Phenotype MicroArrays followed by specific growth studies and mutational analysis to understand how catabolism is regulated by this sensor kinase system in the biocontrol isolate, Pseudomonas chlororaphis O6. Growth of a gacS mutant was decreased significantly compared to that of the wild-type on ornithine and arginine, and the precursor of these amino acids, N-acetyl-l-glutamic acid. The gacS mutant also showed reduced production of polyamines. Expression of the genes encoding arginine decarboxylase (speA) and ornithine decarboxylases (speC) was controlled at the transcriptional level by the GacS sensor of P. chlororaphis O6. Polyamine production was reduced in the speC mutant, and was eliminated in the speAspeC mutant. Addition of exogenous polyamines to the speAspeC mutant restored in vitro growth inhibition of two fungal pathogens as well as the secretion of three biological control-related factors, pyrrolnitrin, protease, and siderophore. These results extend our knowledge of regulation by the Gac/Rsm network in a biocontrol pseudomonad to include polyamine synthesis. Collectively our studies demonstrate that bacterial polyamines act as important regulators of bacterial cell growth and biocontrol potential. This article is protected by copyright. All rights reserved. © 2017 BSPP and John Wiley & Sons Ltd.

  10. High-performance liquid chromatographic determination of polyamines in milk as their 9-fluorenylmethoxycarbonyl derivatives using a column-switching technique.

    Science.gov (United States)

    Bellagamba, F; Moretti, V M; Mentasti, T; Albertini, A; Luzzana, U; Valfrè, F

    1997-12-12

    A high-performance liquid chromatographic method for the determination of polyamines in milk is milk is described. Polyamines were extracted in perchloric acid and derivatized with 9-fluorenylmethoxycarbonyl chloride (FMOC-Cl). The excess of reagent was reacted with aspartic acid before the analysis on a column-switching system. Linearity of derivatization was calculated for each amine and the coefficient of regression ranged from 0.994 to 0.999. Chromatographic separation of FMOC-polyamines was achieved with a gradient elution programme of water-acetonitrile. The correlation coefficients of the standard curves in the concentration range from 0.5 to 5 nmol ml-1 were higher than 0.991. The repeatability of the method, expressed as R.S.D. for each polyamines ranged from 3.0 to 8.6%. The percent mean recoveries at 1 nmol ml-1 spiking level were 49 +/- 3, 58 +/- 5, 61 +/- 5 and 48 +/- 4 for putrescine, cadaverine, spermidine and spermine, respectively. The limit of detection, calculated on the basis of three times signal-to-noise ratio, was 50 pmol ml-1 for each polyamine.

  11. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

    Science.gov (United States)

    Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

    2009-10-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

  12. A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

    Science.gov (United States)

    Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

    2009-01-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

  13. Barium depletion in hollow cathode emitters

    Energy Technology Data Exchange (ETDEWEB)

    Polk, James E., E-mail: james.e.polk@jpl.nasa.gov; Mikellides, Ioannis G.; Katz, Ira [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91109 (United States); Capece, Angela M. [Graduate Aerospace Laboratories, California Institute of Technology, Pasadena, California 91125 (United States)

    2016-01-14

    Dispenser hollow cathodes rely on a consumable supply of Ba released by BaO-CaO-Al{sub 2}O{sub 3} source material in the pores of a tungsten matrix to maintain a low work function surface. The examination of cathode emitters from long duration tests shows deposits of tungsten at the downstream end that appear to block the flow of Ba from the interior. In addition, a numerical model of Ba transport in the cathode plasma indicates that the Ba partial pressure in the insert may exceed the equilibrium vapor pressure of the dominant Ba-producing reaction, and it was postulated previously that this would suppress Ba loss in the upstream part of the emitter. New measurements of the Ba depletion depth from a cathode insert operated for 8200 h reveal that Ba loss is confined to a narrow region near the downstream end, confirming this hypothesis. The Ba transport model was modified to predict the depletion depth with time. A comparison of the calculated and measured depletion depths gives excellent qualitative agreement, and quantitative agreement was obtained assuming an insert temperature 70 °C lower than measured beginning-of-life values.

  14. Mitochondrial DNA depletion analysis by pseudogene ratioing.

    Science.gov (United States)

    Swerdlow, Russell H; Redpath, Gerard T; Binder, Daniel R; Davis, John N; VandenBerg, Scott R

    2006-01-30

    The mitochondrial DNA (mtDNA) depletion status of rho(0) cell lines is typically assessed by hybridization or polymerase chain reaction (PCR) experiments, in which the failure to hybridize mtDNA or amplify mtDNA using mtDNA-directed primers suggests thorough mitochondrial genome removal. Here, we report the use of an mtDNA pseudogene ratioing technique for the additional confirmation of rho0 status. Total genomic DNA from a U251 human glioma cell line treated with ethidium bromide was amplified using primers designed to anneal either mtDNA or a previously described nuclear DNA-embedded mtDNA pseudogene (mtDNApsi). The resultant PCR product was used to generate plasmid clones. Sixty-two plasmid clones were genotyped, and all arose from mtDNApsi template. These data allowed us to determine with 95% confidence that the resultant mtDNA-depleted cell line contains less than one copy of mtDNA per 10 cells. Unlike previous hybridization or PCR-based analyses of mtDNA depletion, this mtDNApsi ratioing technique does not rely on interpretation of a negative result, and may prove useful as an adjunct for the determination of rho0 status or mtDNA copy number.

  15. N-Carbamoylputrescine, a citrulline-derived polyamine, is not a significant citrulline metabolite in rats.

    Science.gov (United States)

    Ramani, D; Nakib, S; Chen, H; Garbay, C; Loukaci, A; Cynober, L; De Bandt, J P

    2012-04-01

    Citrulline, a key amino acid of the urea cycle, has been shown to play a regulatory role in protein and energy metabolism in mammals. We questioned whether N-carbamoyl-putrescine (NCP), the decarboxylated derivative of citrulline, could play a role in the biological properties of this amino acid. To evidence the presence of NCP in mammalian tissues, we developed a sensitive reverse-phase high-performance liquid chromatography (HPLC) with fluorimetric detection method with precolumn dansyl derivatization and solid-phase extraction for the determination of NCP together with polyamines in biological samples. Dansyl NCP was identified with a 5.85-min retention time. Linearity was obtained in a concentration range of 0.125 to 12.5 μM. Intraday and day-to-day relative coefficients of variation ranged from 8.9% to 12.3% and from 14% to 14.3%, respectively. Recovery rates in serum ranged from 75% to 83%. Thereafter, we used this method to search for the presence of NCP in serum, muscle, liver, jejunum, and ileum in rats after both short-term intraperitoneal injection and long-term oral citrulline supplementation. We failed to detect NCP in these animals. These data suggest that NCP is not a significant citrulline metabolite in rats.

  16. The relationship between polyamines and hormones in the regulation of wheat grain filling.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available The grain weight of wheat is strongly influenced by filling. Polyamines (PA are involved in regulating plant growth. However, the effects of PA on wheat grain filling and its mechanism of action are unclear. The objective of the present study was to investigate the relationship between PAs and hormones in the regulation of wheat grain filling. Three PAs, spermidine (Spd, spermine (Spm, and putrescine (Put, were exogenously applied, and the grain filling characteristics and changes in endogenous PA and hormones, i.e., indole-3-acetic acid (IAA, zeatin (Z + zeatin riboside (ZR, abscisic acid (ABA, ethylene (ETH and gibberellin 1+4 (GAs, were quantified during wheat grain filling. Exogenous applications of Spd and Spm significantly increased the grain filling rate and weight, but exogenous Put had no significant effects on these measures. Exogenous Spd and Spm significantly increased the endogenous Spd, Spm, Z+ZR, ABA, and IAA contents and significantly decreased ETH evolution in grains. The endogenous Spd, Spm and Z+ZR contents were positively and significantly correlated with the grain filling rate and weight of wheat, and the endogenous ETH evolution was negatively and significantly correlated with the wheat grain filling rate and weight. Based upon these results, we concluded that PAs were involved in the balance of hormones that regulated the grain filling of wheat.

  17. Effect of salicylic acid treatment on postharvest quality, antioxidant activities, and free polyamines of asparagus.

    Science.gov (United States)

    Wei, Yunxiao; Liu, Zhenfeng; Su, Yujing; Liu, Donghong; Ye, Xingqian

    2011-03-01

    The effects of salicylic acid (SA) on the quality and antioxidant activity of asparagus stored at 18 ± 2 °C were investigated by analyzing the color, chlorophyll, shear force, and the activity of antioxidant compounds such as ascorbic acid, phenolics, flavonoids, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity ferric reducing antioxidant power (FRAP), and polyamines (PAs). The results showed that SA improved the color and maintained the chlorophyll, phenolic, flavonoid, and ascorbic acid content of asparagus. High concentrations of SA caused a deterioration in asparagus would harm to color and had no effect on shear force within 6 d. SA induced the maximum concentration of phenolics in postharvest asparagus, promoted the increase in total flavonoids before 6 to 9 d, affected the antioxidant activity positively as indicated by the resultant increase in FRAP concentration; however, SA was only active with regard to DPPH scavenging activity within 6 d of treatment. Spermidine (Spd) is the most common form of PA in asparagus, and free putrescine (Put) contents increased over the first 3 d following harvest and then decreased. Spd and Spm concentrations evolved in a similar way and decreased during storage. Higher Spd and Spm contents in the SA pre-treatment Put was inhabited and its peaks appeared later.

  18. [Relationship between chloride tolerance and polyamine accumulation in Glycine max, Glycine soja, and their hybrid seedlings].

    Science.gov (United States)

    Chen, Xuan-Qin; Yu, Bing-Jun; Liu, You-Liang

    2007-02-01

    The seedlings of the F4 hybrid strain 'JB185' selected for salt tolerance generation by generation, their parents Glycine max cv. Jackson and Glycine soja population 'BB52' were treated with different NaCl concentrations and iso-osmotic (-0.53 MPa) PEG-6000, NaCl, Na+ (without Cl-) and Cl- (without Na+) solutions for 6 d. The results showed that: (1) The relative electrolyte leakage and malondialdehyde (MDA) content in leaves of the above three soybean seedlings showed an increase trend when the NaCl concentration was elevated, but chlorophyll contents decreased except the significant increase in 'BB52' and 'JB185' under NaCl 50 mmol/L stress. The change in 'JB185' was between its parents. (2) Under different iso-osmotic stresses, the relative electrolyte leakage and MDA contents in leaves of three soybean seedlings also increased mostly, the changes in 'BB52' and 'JB185' under Na+ (without Cl-) stress were more than those under Cl- (without Na+) stress. The free and bound Put, Spd and Spm contents in leaves all increased when compared with the control, the ratios of free (Spd+Spm)/Put and total bound polyamines in 'BB52' and 'JB185' seedlings under Na+ (without Cl-) treatment were the lowest one among three iso-osmotic salt stresses. The results indicate that the F4 hybrid strain 'JB185' is more sensitive to Na+ than Cl- as its wild parent 'BB52' population.

  19. The Relationship between Polyamines and Hormones in the Regulation of Wheat Grain Filling

    Science.gov (United States)

    Liu, Yang; Gu, Dandan; Wu, Wei; Wen, Xiaoxia; Liao, Yuncheng

    2013-01-01

    The grain weight of wheat is strongly influenced by filling. Polyamines (PA) are involved in regulating plant growth. However, the effects of PA on wheat grain filling and its mechanism of action are unclear. The objective of the present study was to investigate the relationship between PAs and hormones in the regulation of wheat grain filling. Three PAs, spermidine (Spd), spermine (Spm), and putrescine (Put), were exogenously applied, and the grain filling characteristics and changes in endogenous PA and hormones, i.e., indole-3-acetic acid (IAA), zeatin (Z) + zeatin riboside (ZR), abscisic acid (ABA), ethylene (ETH) and gibberellin 1+4 (GAs), were quantified during wheat grain filling. Exogenous applications of Spd and Spm significantly increased the grain filling rate and weight, but exogenous Put had no significant effects on these measures. Exogenous Spd and Spm significantly increased the endogenous Spd, Spm, Z+ZR, ABA, and IAA contents and significantly decreased ETH evolution in grains. The endogenous Spd, Spm and Z+ZR contents were positively and significantly correlated with the grain filling rate and weight of wheat, and the endogenous ETH evolution was negatively and significantly correlated with the wheat grain filling rate and weight. Based upon these results, we concluded that PAs were involved in the balance of hormones that regulated the grain filling of wheat. PMID:24205154

  20. Effect of polyamine biosynthetic inhibitors on alkaloids and organogenesis in tobacco callus cultures.

    Science.gov (United States)

    Tiburcio, A F; Kaur-Sawhney, R; Galston, A W

    1987-01-01

    We studied the effects of inhibitors of ornithine decarboxylase (ODC), arginine decarboxylase (ADC) and spermidine synthase (Spd synthase) on organogenesis and the titers of polyamines (PA) and alkaloids in tobacco calli. DL-alpha-diffluromethylarginine (DFMA) and D-arginine (D-Arg), both inhibitors of ADC activity, were more effective than DL-alpha-difluromethylorinithine (DFMO), an inhibitor of ODC, in reducing titers of PA and the putrescine (Put)-derived alkaloids (nornicotine and nicotine). Dicyclohexylammonium sulfate (DCHA), an inhibitor of Spd synthase, was also more efficient than DFMO in reducing PA and alkaloid levels. Root organogenesis is inversely related to the titers of Put and alkaloids. Thus, DFMA and D-Arg, which strongly inhibit Put and alkaloid biosynthesis, markedly promote root organogenesis, while control callus with high Put and alkaloid content showed poor root organization. These results suggest that morphological differentiation is not required for activation of secondary metabolic pathways and support the view that ADC has a major role in the generation of Put going to the pyrrolidine ring of tobacco alkaloids.

  1. In vivo inhibition of polyamine biosynthesis and growth in tobacco ovary tissues.

    Science.gov (United States)

    Slocum, R D; Galston, A W

    1985-01-01

    Post fertilization growth of tobacco ovary tissues treated with inhibitors of polyamine (PA) biosynthesis was examined in relation to endogenous PA titers and the activities of arginine decarboxylase (ADC, EC 4.1.1.19) and ornithine decarboxylase (ODC, EC 4.1.1.17). DL-alpha-Difluoromethylornithine (DFMO) and DL-alpha-difluoromethylarginine (DFMA), specific, irreversible ("suicide") inhibitors of ODC and ADC in vitro, were used to modulate PA biosynthesis in excised flowers. ODC represented >99% of the total decarboxylase activity in tobacco ovaries. In vivo inhibition of ODC with DFMO resulted in a significant decrease in PA titers, ovary fresh weight and protein content. Simultaneous inhibition of both decarboxylases by DFMO and DFMA produced only a marginally greater depression in growth and PA titers, indicating that ODC activity is rate-limiting for PA biosynthesis in these tissues. Paradoxically, DFMA alone inhibited PA biosynthesis, not as a result of a specific inhibition of ADC, but primarily through the inactivation of ODC. In vivo inhibition of ODC by DFMA appears to result from arginase-mediated hydrolysis of this inhibitor to urea and DFMO, the suicide substrate for ODC. Putrescine conjugates in tobacco appear to function as a storage form of this amine which, upon hydrolysis, may contribute to Put homeostasis during growth.

  2. From biosilicification to tailored materials: Optimizing hydrophobic domains and resistance to protonation of polyamines

    Science.gov (United States)

    Belton, David J.; Patwardhan, Siddharth V.; Annenkov, Vadim V.; Danilovtseva, Elena N.; Perry, Carole C.

    2008-01-01

    Considerable research has been directed toward identifying the mechanisms involved in biosilicification to understand and possibly mimic the process for the production of superior silica-based materials while simultaneously minimizing pollution and energy costs. Molecules isolated from diatoms and, most recently sponges, thought to be key to this process contain polyamines with a propylamine backbone and variable levels of methylation. In a chemical approach to understanding the role of amine (especially propylamine) structures in silicification we have explored three key structural features: (i) the degree of polymerization, (ii) the level of amine methylation, and (iii) the size of the amine chain spacers. In this article, we show that there are two factors critical to their function: the ability of the amines to produce microemulsions and the presence of charged and uncharged amine groups within a molecule, with the latter feature helping to catalyze silicic acid condensation by a proton donor/acceptor mechanism. The understanding of amine–silicate interactions obtained from this study has enabled the controlled preparation of hollow and nonporous siliceous materials under mild conditions (circumneutral pH, room temperature, and in all aqueous systems) possibly compatible with the conditions used by biosystems. The “rules” identified from our study were further used predictively to modulate the activity of a given amine. We believe that the outcomes of the present contribution will form the basis for an approach to controlling the growth of inorganic materials by using tailor-made organic molecules. PMID:18420819

  3. Physiological and molecular implications of plant polyamine metabolism during biotic interactions

    Directory of Open Access Journals (Sweden)

    Juan Francisco Jiménez Bremont

    2014-03-01

    Full Text Available During ontogeny, plants interact with a wide variety of microorganisms. The association with mutualistic microbes results in benefits for the plant. By contrast, pathogens may cause a remarkable impairment of plant growth and development. Both types of plant-microbe interactions provoke notable changes in the polyamine (PA metabolism of the host and/or the microbe, being each interaction a complex and dynamic process. It has been well documented that the levels of free and conjugated PAs undergo profound changes in plant tissues during the interaction with microorganisms. In general, this is correlated with a precise and coordinated regulation of PA biosynthetic and catabolic enzymes. Interestingly, some evidence suggests that the relative importance of these metabolic pathways may depend on the nature of the microorganism, a concept that stems from the fact that these amines mediate the activation of plant defense mechanisms. This effect is mediated mostly through PA oxidation, even though part of the response is activated by non-oxidized PAs. In the last years, a great deal of effort has been devoted to profile plant gene expression following microorganism recognition. In addition, the phenotypes of transgenic and mutant plants in PA metabolism genes have been assessed. In this review, we integrated the current knowledge on this field and analyze the possible roles of these amines during the interaction of plants with microbes.

  4. Aminopropyltransferases involved in polyamine biosynthesis localize preferentially in the nucleus of plant cells.

    Directory of Open Access Journals (Sweden)

    Borja Belda-Palazón

    Full Text Available Plant aminopropyltransferases consist of a group of enzymes that transfer aminopropyl groups derived from decarboxylated S-adenosyl-methionine (dcAdoMet or dcSAM to propylamine acceptors to produce polyamines, ubiquitous metabolites with positive charge at physiological pH. Spermidine synthase (SPDS uses putrescine as amino acceptor to form spermidine, whereas spermine synthase (SPMS and thermospermine synthase (TSPMS use spermidine as acceptor to synthesize the isomers spermine and thermospermine respectively. In previous work it was shown that both SPDS1 and SPDS2 can physically interact with SPMS although no data concerning the subcellular localization was reported. Here we study the subcellular localization of these enzymes and their protein dimer complexes with gateway-based Bimolecular Fluorescence Complementation (BiFC binary vectors. In addition, we have characterized the molecular weight of the enzyme complexes by gel filtration chromatography with in vitro assembled recombinant enzymes and with endogenous plant protein extracts. Our data suggest that aminopropyltransferases display a dual subcellular localization both in the cytosol and nuclear enriched fractions, and they assemble preferably as dimers. The BiFC transient expression data suggest that aminopropyltransferase heterodimer complexes take place preferentially inside the nucleus.

  5. Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis.

    Science.gov (United States)

    Luke, Courtney T; Casta, Alexandre; Kim, Hyunmi; Christiano, Angela M

    2013-10-01

    Hairless (HR) is a nuclear protein with corepressor activity that is highly expressed in the skin and hair follicle. Mutations in Hairless lead to hair loss accompanied by the appearance of papules (atrichia with papular lesions), and similar phenotypes appear when the key polyamine enzymes ornithine decarboxylase (ODC) and spermidine/spermine N(1) -acetyltransferase (SSAT) are overexpressed. Both ODC and SSAT transgenic mice have elevated epidermal levels of putrescine, leading us to investigate the mechanistic link between putrescine and HR. We show here that HR and putrescine form a negative regulatory network, as epidermal ODC expression is elevated when HR is decreased and vice versa. We also show that the regulation of ODC by HR is dependent on the MYC superfamily of proteins, in particular MYC, MXI1 and MXD3. Furthermore, we found that elevated levels of putrescine lead to decreased HR expression, but that the SSAT-TG phenotype is distinct from that found when HR is mutated. Transcriptional microarray analysis of putrescine-treated primary human keratinocytes demonstrated differential regulation of genes involved in protein-protein interactions, nucleotide binding and transcription factor activity, suggesting that the putrescine-HR negative regulatory loop may have a large impact on epidermal homeostasis and hair follicle cycling.

  6. Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Gong, Zheng; Tang, M Matt; Wu, Xueliang; Phillips, Nancy; Galkowski, Dariusz; Jarvis, Gary A; Fan, Huizhou

    2016-01-01

    Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

  7. Antagonistic effect of polyamines on ABA-induced suppression of mitosis in Allium cepa L.

    Science.gov (United States)

    Mahajan, Arpana; Sharma, Shashi

    2009-02-01

    Effect of abscisic acid (ABA) and polyamines (PAs) [putrescine (Put), spermidine (Spd) and spermine (Spm)] on mitosis in root tips of A. cepa was studied. Treatment with ABA (0.1 to 100 microM) for 24 hr suppressed the mitosis, measured as mitotic index (MI), in a concentration-dependent manner with approx. 50% suppression at 10 microM of ABA. Treatment with different PAs (1 to 100 microM) had differential mitosis suppression effect. Spm was most inhibitory followed by Spd and Put, respectively. The higher concentrations of PAs (1 mM Put; 0.1 and 1 mM Spd or Spm) caused cell distortion. Remarkably, a 24 hr pretreatment of root tips with PAs prior to ABA (100 microM) treatment resulted in a general concentration-dependent reversal of ABA-induced suppression of MI. Catalase (CAT) activity in the root tips, an indicator of redox metabolism, increased due to ABA treatment in a concentration-dependent manner, remained unaltered in response to Put and declined due to Spd and Spm (> or = 0.1 mM). However, all PAs, irrespective of their individual effects, generally antagonized the ABA-dependent increase in CAT activity. Data indicate the possibility of ABA-PA interaction in the regulation of mitosis.

  8. Investigation of indolglyoxamide and indolacetamide analogues of polyamines as antimalarial and antitrypanosomal agents.

    Science.gov (United States)

    Wang, Jiayi; Kaiser, Marcel; Copp, Brent R

    2014-05-28

    Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC50 59 and 44 μM, respectively) and Plasmodium falciparum (K1 dual drug resistant strain) (IC50 41 and 15 μM, respectively), but lacking in selectivity (L6 rat myoblast, IC50 24 μM and 25 μM, respectively). To expand the structure-activity relationship of this compound class towards both parasites, we have prepared and biologically tested a library of analogues that includes indoleglyoxyl and indoleacetic "capping acids", and polyamines including spermine (PA3-4-3) and extended analogues PA3-8-3 and PA3-12-3. 7-Methoxy substituted indoleglyoxylamides were typically found to exhibit the most potent antimalarial activity (IC50 10-92 nM) but with varying degrees of selectivity versus the L6 rat myoblast cell line. A 6-methoxyindolglyoxylamide analogue was the most potent growth inhibitor of T. brucei (IC50 0.18 μM) identified in the study: it, however, also exhibited poor selectivity (L6 IC50 6.0 μM). There was no apparent correlation between antimalarial and anti-T. brucei activity in the series. In vivo evaluation of one analogue against Plasmodium berghei was undertaken, demonstrating a modest 20.9% reduction in parasitaemia.

  9. Effects of osmotic stress on the kinds, forms and levels of polyamines in wheat coleoptiles.

    Science.gov (United States)

    Liu, Huai-Pan; Zhu, Zi-Xue; Liu, Tian-Xue; Li, Chao-Hai

    2006-06-01

    The changes in levels and forms of polyamine (Pa) in the coleoptiles of two wheat (triticum aestivum L.) cultivars differing in drought tolerance were investigated under osmotic stress. The drought-tolerant 'Yumai 18' showed marked increases in free spermidine (Spd) and spermine (Spm) levels in coleoptiles after being treated with polyethylene glycol (PEG)-6000 for 2 d in the dark, while drought-sensitive 'Yangmai 9' showed a significant increase in free putrescine (Put) content. Treatment of coleoptiles with methylglyoxal-bis (guanylhydrazone) (MGBG), an S-adenosylmethionine decarboxylase (S-AMDC) inhibitor, resulted in reduction of free Spd and free Spm levels in coleoptiles and aggravation of PEG-induced injury to 'Yumai 18' coleoptile, while exogenous Spd treatment resulted in an increase in free Spd + free Spm content of coleoptiles, and an alleviation of PEG-induced injury to 'Yangmai 9' coleoptile. Osmotic stress induced significant increases in perchloric acid-soluble conjugated PA (PS conjugated PA) and perchloric acid-insoluble conjugated PA (PIS conjugated PA) levels in coleoptiles of 'Yumai 18' whereas osmotic stress affected only slightly the PS-conjugated PA and PIS-conjugated PA levels in 'Yangmai 9' coleoptiles. Treatment of coleoptiles with phenanthroline (o-Phen), an inhibitor of transglutaminase (TGase), also aggravated the PEG-induced injury to 'Yumai 18' coleoptiles, accompanied by the decreases in the level of PIS-conjugated PA. These results suggest that free Spd, free Spm and conjugated PA enhance the osmotic stress tolerance of wheat coleoptiles.

  10. Incorporation of radiolabeled polyamines and methionine into turnip yellow mosaic virus in protoplasts from infected plants

    Energy Technology Data Exchange (ETDEWEB)

    Balint, R.; Cohen, S.S.

    1985-07-15

    Turnip yellow mosaic virus contains large amounts of nonexchangeable spermidine and induces an accumulation of spermidine in infected Chinese cabbage. By 7 days after inoculation, a majority of protoplasts isolated from newly emerging leaves stain with fluorescent antibody to the virus. (/sup 14/C)Spermidine (10 microM) was taken up by these cells in amounts comparable to the original endogenous pool within 24 hr. However, after an initial rise, the spermidine content of the cell returned to its original level, implying considerable regulation of the endogenous pool(s). Putrescine and spermine were major products of the metabolism of exogenous spermidine. Radioactivity from exogenous (/sup 14/C)spermidine was also readily incorporated into the ribonucleoprotein component(s) of the virus, where it appeared as both spermidine and spermine. The specific radioactivities of the viral polyamines were approximately twice those of spermidine and spermine extracted from the whole cell. Radioactivity from (2-/sup 14/C)methionine was readily incorporated into the protein, spermidine, and spermine of the virus. Again,