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Sample records for arginine vasopressin-neurophysin ii

  1. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

    NARCIS (Netherlands)

    Fost, M. de; Trotsenburg, A.S. van; Santen, H.M. van; Endert, E.; Elzen, C. van den; Kamsteeg, E.J.; Swaab, D.F.; Fliers, E.A.

    2011-01-01

    BACKGROUND: Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with

  2. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

    NARCIS (Netherlands)

    de Fost, M.; van Trotsenburg, A. S. P.; van Santen, H. M.; Endert, E.; van den Elzen, C.; Kamsteeg, E. J.; Swaab, D. F.; Fliers, E.

    2011-01-01

    Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal

  3. A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: Cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Rutishauser, J.; Boeni-Schnetzler, M.; Froesch, E.R.; Wichmann, W.; Huisman, T. [Univ. of Zuerich (Switzerland)] [and others

    1996-01-01

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare variant of idiopathic central diabetes insipidus. Several different mutations in the human vasopressin-neurophysin II (AVP-NP II) gene have been described. We studied nine family members from three generations of an ADNDI pedigree at the clinical, morphological, and molecular levels. AVP concentrations were measured during diagnostic fluid restriction tests. Coronal and sagittal high resolution T1-weighted images of the pituitary were obtained from affected and healthy family members. PCR was used to amplify the AVP-NP II precursor gene, and PCR products were directly sequenced. Under maximal osmotic stimulation, AVP serum levels were close to or below the detection limit in affected individuals. Magnetic resonance imaging studies revealed the characteristic hyperintense ({open_quotes}bright spot{close_quotes}) appearance of the posterior pituitary in two healthy family members. This signal was absent in all four ADNDI patients examined. The coding sequences of AVP and its carrier protein, neurophysin II, were normal in all family members examined. Affected individuals showed a novel single base deletion (G 227) in the translation initiation codon of the AVP-NP II signal peptide on one allele. The mutation in the AVP-NP II leader sequence appears to be responsible for the disease in this kindred, possibly by interfering with protein translocation. The absence of the hyperintense posterior pituitary signal in affected individuals could reflect deficient posterior pituitary function. 56 refs., 4 figs., 3 tabs.

  4. Synthesis, characterization and behaviour of trans-bis (argininate) copper (II) to gamma radiation

    International Nuclear Information System (INIS)

    Pereira, A.B.

    1984-01-01

    The synthesis, the characterization and the behaviour to gamma radiation of trans-bis (argininate) copper (II) are presented. The synthesis is made from copper sulfate, sodium hydroxide and hydrochloride of L (+) arginine, in aqueous medium, and the characterization by infrared spectroscopy, visible and ultraviolet spectroscopy and elementary analysis. (C.G.C.)

  5. The arginine methyltransferase PRMT5 regulates CIITA-dependent MHC II transcription.

    Science.gov (United States)

    Fan, Zhiwen; Kong, Xiaocen; Xia, Jun; Wu, Xiaoyan; Li, He; Xu, Huihui; Fang, Mingming; Xu, Yong

    2016-05-01

    Class II major histocompatibility complex (MHC II) dependent antigen presentation serves as a key step in mammalian adaptive immunity and host defense. In antigen presenting cells (e.g., macrophages), MHC II transcription can be activated by interferon gamma (IFN-γ) and mediated by class II transactivator (CIITA). The underlying epigenetic mechanism, however, is not completely understood. Here we report that following IFN-γ stimulation, symmetrically dimethylated histone H3 arginine 2 (H3R2Me2s) accumulated on the MHC II promoter along with CIITA. IFN-γ augmented expression, nuclear translocation, and promoter binding of the protein arginine methyltransferase PRMT5 in macrophages. Over-expression of PRMT5 potentiated IFN-γ induced activation of MHC II transcription in an enzyme activity-dependent manner. In contrast, PRMT5 silencing or inhibition of PRMT5 activity by methylthioadenosine (MTA) suppressed MHC II transactivation by IFN-γ. CIITA interacted with and recruited PRMT5 to the MHC II promoter and mediated the synergy between PRMT5 and ASH2/WDR5 to activate MHC II transcription. PRMT5 expression was down-regulated in senescent and H2O2-treated macrophages rendering ineffectual induction of MHC II transcription by IFN-γ. Taken together, our data reveal a pathophysiologically relevant role for PRMT5 in MHC II transactivation in macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Ni(II) complexes of arginine Schiff-bases and its interaction with DNA

    International Nuclear Information System (INIS)

    Sallam, S.A.; Abbas, A.M.

    2013-01-01

    Ni(II) complexes with Schiff-bases obtained by condensation of arginine with salicylaldehyde; 2,3-; 2,4-; 2,5-dihydroxybenzaldehyde and o-hydroxynaphthaldehyde have been synthesized using the template method in ethanol or ammonia media. They were characterized by elemental analyses, conductivity measurements, magnetic moment, UV, IR and 1 H NMR spectra as well as thermal analysis (TG, DTG and DTA). The Schiff-bases are dibasic tridentate donors and the complexes have diamagnetic square planar and octahedral structures. The complexes decompose in three steps where kinetic and thermodynamic parameters of the decomposition steps were computed. The interactions of the formed complexes with FM-DNA were monitored by UV and fluorescence spectroscopy. -- Highlights: ► Arginine Schiff-bases and their nickel(II) complexes have been synthesized. ► Magnetic and spectral data show diamagnetic square planar and octahedral complexes. ► The complexes thermally decompose in three stages. Interaction with FM-DNA shows hyperchromism with blue shift

  7. Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene.

    Directory of Open Access Journals (Sweden)

    Jungtae Na

    Full Text Available Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5 as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when the Per1 gene was repressed both in synchronized mouse liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the Per1 gene promoter was found to be associated with an increased level of histone H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3 dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5-depleted cells. Taken together, these findings provide an insight into the link between histone arginine methylation by PRMT5 and transcriptional regulation of the circadian Per1 gene.

  8. Vasopressin-neurophysin and DST in major depression: relationship with suicidal behavior.

    Science.gov (United States)

    Pitchot, William; Scantamburlo, Gabrielle; Pinto, Emmanuel; Hansenne, Michel; Reggers, Jean; Ansseau, Marc; Legros, Jean-Jacques

    2008-07-01

    The purpose of the present study was to assess if AVP-neurophysin is associated with hypercortisolemia and suicidal behaviour in depressed patients. The study included 28 patients subgrouped into suicide attempters (n=13) and nonattempters (n=15). We assessed basal AVP-neurophysins concentrations and post-dexamethasone (DST) cortisol levels. Concentrations of AVP-neurophysins did not differ between DST suppressors and nonsuppressors: 0.29+/-0.13 ng/ml vs 0.36+/-0.21 ng/ml, (F=1.1, df=1, 27, p=0.30). Suicide attempters did not differ from nonattempters for AVP-neurophysins levels. Our results fail to support a role of AVP in the early cortisol escape.

  9. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling.

    Science.gov (United States)

    Xiong, Yuyan; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-05-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells.

  10. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

    Science.gov (United States)

    Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-01-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells. PMID:24860943

  11. Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation

    DEFF Research Database (Denmark)

    Siggaard, C; Rittig, S; Corydon, T J

    1999-01-01

    of AVP-NPII [Ala(-1)Thr]. Genetic analysis and clinical studies of AVP secretion, urinary AVP, and urine output were performed in 16 affected and 16 unaffected family members and 11 spouses of a Danish adFNDI kindred carrying the Ala(-1)Thr mutation. Mutant complementary DNA carrying the same mutation......The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations...... of the gene that codes for the vasopressin-neurophysin II (AVP-NPII) precursor. The aims of the present study were to relate the clinical phenotype to the specific genotype and to the molecular genetic effects of the most frequently reported adFNDI mutation located at the cleavage site of the signal peptide...

  12. Plasma vasopressin, neurophysin, renin and aldosterone during a 4-day head-down bed rest with and without exercise.

    Science.gov (United States)

    Annat, G; Güell, A; Gauquelin, G; Vincent, M; Mayet, M H; Bizollon, C A; Legros, J J; Pottier, J M; Gharib, C

    1986-01-01

    The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is currently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (-6 degrees) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% VO2max) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.

  13. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling.

    OpenAIRE

    Xiong Yuyan; Fru Michael Forbiteh; Yu Yi; Montani Jean-Pierre; Ming Xiu-Fen; Yang Zhihong

    2014-01-01

    L arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However controversial results and even detrimental effects of L arginine supplementation are reported. We investigate potential mechanisms of L arginine induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L arginine for 30 minutes (acute)...

  14. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

    OpenAIRE

    Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-01-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute...

  15. L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Taylor Claybaugh

    2014-01-01

    Full Text Available Rat studies demonstrated that type II diabetes mellitus (T2DM decreases both the production and bioavailability of nitric oxide (NO. L-arginine (LA provides the precursor for the production of NO. We hypothesized that LA dietary supplementation will preserve NO production via endothelial nitric oxide synthase (eNOS causing renal microvascular vasodilation and increased glomerular blood flow and thus increasing glomerular filtration rate (GFR. This would impede the formation of reactive oxygen species which contributes to cell damage and death. LA supplementation preserved GFR in the treated diabetic rats compared to untreated diabetic rats. We provide evidence that this effect may be due to increased levels of eNOS and urinary cyclic guanosine monophosphate, which leads to renal microvascular vasodilation. Plasma nitrotyrosine was decreased in the LA treated rats; however, plasma nitrite levels remained unaffected as expected. Marked improvements in glucose tolerance were also observed in the LA treated diabetic rats. These results demonstrate that LA supplementation preserves NO activity and may delay the onset of insulin resistance and renal dysfunction during hyperglycemic stress. These results suggest the importance of the NO pathway in consequent renal dysfunction and in the development of insulin resistance in diabetic rats.

  16. L-Arginine

    Science.gov (United States)

    ... with this combination.Talk with your health provider.Sildenafil (Viagra)Sildenafil (Viagra) can lower blood pressure. L-arginine can also lower blood pressure. Taking sildenafil (Viagra) and L-arginine together might cause the ...

  17. Genetic forms of neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Rutishauser, Jonas; Spiess, Martin; Kopp, Peter

    2016-03-01

    Neurohypophyseal diabetes insipidus is characterized by polyuria and polydipsia owing to partial or complete deficiency of the antidiuretic hormone, arginine vasopressin (AVP). Although in most patients non-hereditary causes underlie the disorder, genetic forms have long been recognized and studied both in vivo and in vitro. In most affected families, the disease is transmitted in an autosomal dominant manner, whereas autosomal recessive forms are much less frequent. Both phenotypes can be caused by mutations in the vasopressin-neurophysin II (AVP) gene. In transfected cells expressing dominant mutations, the mutated hormone precursor is retained in the endoplasmic reticulum, where it forms fibrillar aggregates. Autopsy studies in humans and a murine knock-in model suggest that the dominant phenotype results from toxicity to vasopressinergic neurons, but the mechanisms leading to cell death remain unclear. Recessive transmission results from AVP with reduced biologic activity or the deletion of the locus. Genetic neurohypophyseal diabetes insipidus occurring in the context of diabetes mellitus, optic atrophy, and deafness is termed DIDMOAD or Wolfram syndrome, a genetically and phenotypically heterogeneous autosomal recessive disorder caused by mutations in the wolframin (WFS 1) gene. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Effect of repeated pesticide applications on soil properties in cotton fields: II. Insecticide residues and impact on dehydrogenase and arginine deaminase activities

    International Nuclear Information System (INIS)

    Vig, K.; Singh, D.K.; Agarwal, H.C.; Dhawan, A.K.; Dureja, P.

    2001-01-01

    Insecticides were applied sequentially at recommended dosages post crop emergence in cotton fields and soil was sampled at regular intervals after each treatment. Soil was analysed for insecticide residues and activity of the enzymes dehydrogenase and arginine deaminase. Insecticide residues detected in the soil were in small quantities and they did not persist for long. Only endosulfan leached below 15 cm. Insecticides had only temporary effects on enzyme activities which disappeared either before the next insecticide treatment or by the end of the experimental period. (author)

  19. l-Arginine Availability Modulates Local Nitric Oxide Production and Parasite Killing in Experimental Trypanosomiasis

    OpenAIRE

    Gobert, Alain P.; Daulouede, Sylvie; Lepoivre, Michel; Boucher, Jean Luc; Bouteille, Bernard; Buguet, Alain; Cespuglio, Raymond; Veyret, Bernard; Vincendeau, Philippe

    2000-01-01

    Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages from Trypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence of l-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows that l-arginine availability modulates NO production. Trypanosomes use l-arginine for polyamine synthesis,...

  20. Reduced arginine availability and nitric oxide production

    NARCIS (Netherlands)

    Hallemeesch, M. M.; Lamers, W. H.; Deutz, N. E. P.

    2002-01-01

    The precursor for nitric oxide (NO) synthesis is the amino acid arginine. Reduced arginine availability may limit NO production. Arginine availability for NO synthesis may be regulated by de novo arginine production from citrulline, arginine transport across the cell membrane, and arginine breakdown

  1. Bioinformatic evaluation of L-arginine catabolic pathways in 24 cyanobacteria and transcriptional analysis of genes encoding enzymes of L-arginine catabolism in the cyanobacterium Synechocystis sp. PCC 6803

    Directory of Open Access Journals (Sweden)

    Pistorius Elfriede K

    2007-11-01

    Full Text Available Abstract Background So far very limited knowledge exists on L-arginine catabolism in cyanobacteria, although six major L-arginine-degrading pathways have been described for prokaryotes. Thus, we have performed a bioinformatic analysis of possible L-arginine-degrading pathways in cyanobacteria. Further, we chose Synechocystis sp. PCC 6803 for a more detailed bioinformatic analysis and for validation of the bioinformatic predictions on L-arginine catabolism with a transcript analysis. Results We have evaluated 24 cyanobacterial genomes of freshwater or marine strains for the presence of putative L-arginine-degrading enzymes. We identified an L-arginine decarboxylase pathway in all 24 strains. In addition, cyanobacteria have one or two further pathways representing either an arginase pathway or L-arginine deiminase pathway or an L-arginine oxidase/dehydrogenase pathway. An L-arginine amidinotransferase pathway as a major L-arginine-degrading pathway is not likely but can not be entirely excluded. A rather unusual finding was that the cyanobacterial L-arginine deiminases are substantially larger than the enzymes in non-photosynthetic bacteria and that they are membrane-bound. A more detailed bioinformatic analysis of Synechocystis sp. PCC 6803 revealed that three different L-arginine-degrading pathways may in principle be functional in this cyanobacterium. These are (i an L-arginine decarboxylase pathway, (ii an L-arginine deiminase pathway, and (iii an L-arginine oxidase/dehydrogenase pathway. A transcript analysis of cells grown either with nitrate or L-arginine as sole N-source and with an illumination of 50 μmol photons m-2 s-1 showed that the transcripts for the first enzyme(s of all three pathways were present, but that the transcript levels for the L-arginine deiminase and the L-arginine oxidase/dehydrogenase were substantially higher than that of the three isoenzymes of L-arginine decarboxylase. Conclusion The evaluation of 24

  2. Dietary arginine and linear growth

    DEFF Research Database (Denmark)

    van Vught, Anneke J A H; Dagnelie, Pieter C; Arts, Ilja C W

    2013-01-01

    and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity......The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School...

  3. Role of arginine and lysine in the antimicrobial mechanism of histone-derived antimicrobial peptides.

    Science.gov (United States)

    Cutrona, Kara J; Kaufman, Bethany A; Figueroa, Dania M; Elmore, Donald E

    2015-12-21

    Translocation of cell-penetrating peptides is often promoted by increased content of arginine or other guanidinium groups. However, relatively little research has considered the role of these functional groups on antimicrobial peptide activity. This study compared the activity of three histone-derived antimicrobial peptides-buforin II, DesHDAP1, and parasin-with variants that contain only lysine or arginine cationic residues. These peptides operate via different mechanisms as parasin causes membrane permeabilization while buforin II and DesHDAP1 translocate into bacteria. For all peptides, antibacterial activity increased with increased arginine content. Higher arginine content increased permeabilization for parasin while it improved translocation for buforin II and DesHDAP1. These observations provide insight into the relative importance of arginine and lysine in these antimicrobial peptides. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. AVP-NPII gene mutations and clinical characteristics of the patients with autosomal dominant familial central diabetes insipidus.

    Science.gov (United States)

    Turkkahraman, Doga; Saglar, Emel; Karaduman, Tugce; Mergen, Hatice

    2015-12-01

    Familial central diabetes insipidus (DI), usually an autosomal dominant disorder, is caused by mutations in arginine vasopressin-neurophysin II (AVP-NPII) gene that leads to aberrant preprohormone processing and gradual destruction of AVP-secreting cells. To determine clinical and molecular characteristics of patients with familial central DI from two different Turkish families. The diagnosis of central DI was established by 24-h urine collection, water deprivation test, and desmopressin challenge. To confirm the diagnosis of familial central DI, the entire coding region of AVP-NPII gene was amplified and sequenced. A total of eight affected patients and three unaffected healthy relatives from two families were studied. Genetic analysis revealed a previously reported heterozygous mutation (p.C98X) in family A, and a heterozygous novel mutation (p.G45C) in family B, both detected in exon 2 of AVP-NPII gene. When we compared the clinical characteristics of the two families, it was noticed that as the age of onset of symptoms in family A ranges between 4 and 7 years, it was <1 year in family B. Additionally, pituitary bright spot was present in the affected siblings, but absent in their affected parents. Familial central DI is a progressive disease, and age of onset of symptoms can differ depending on the mutation. Bright spot on pituitary MRI might be present at onset, but become invisible over time. Genetic testing and appropriate counseling should be given in familial cases of central DI to ensure adequate treatment, and to avoid chronic water deprivation that might result in growth retardation in childhood.

  5. Plasma Copeptin, AVP Gene Variants, and Incidence of Type 2 Diabetes in a Cohort From the Community.

    Science.gov (United States)

    Roussel, Ronan; El Boustany, Ray; Bouby, Nadine; Potier, Louis; Fumeron, Frédéric; Mohammedi, Kamel; Balkau, Beverley; Tichet, Jean; Bankir, Lise; Marre, Michel; Velho, Gilberto

    2016-06-01

    Experimental data support a role for vasopressin in metabolic disorders. We investigated associations of plasma copeptin, a surrogate of vasopressin, and of allelic variations in the arginine vasopressin-neurophysin II gene with insulin secretion, insulin sensitivity, and the risk for impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM). We studied 5110 unrelated French men and women from a prospective cohort of the general population (Data from Epidemiological Study on the Insulin Resistance Syndrome cohort, 9-y follow-up). Six single nucleotide polymorphisms were genotyped. Incidence of IFG or T2DM during follow-up. The incidence of hyperglycemia (IFG/T2DM) during follow-up by quartiles of baseline plasma copeptin was 11.0% (Q1), 14.5% (Q2), 17.0% (Q3), and 23.5% (Q4), log-rank test P = .003. Participants in the upper quartile of plasma copeptin had significantly lower insulin sensitivity (homeostasis model assessment index) at baseline and during follow-up, as compared with other participants. Cox proportional hazards regression analyses showed significant associations of the CC genotype of rs6084264, the TT genotype of rs2282018, the C-allele of rs2770381, and the CC genotype of rs1410713 with the incidence of hyperglycemia. The genotypes associated with an increased risk of hyperglycemia were also associated with increased plasma copeptin in men but not in women. High plasma copeptin was associated with reduced insulin sensitivity and an increased risk for IFG/T2DM diabetes in this community-based cohort. Moreover, in men, allelic associations support a causal role for vasopressin in these disorders.

  6. Characterization of a Novel Arginine Catabolic Mobile Element (ACME) and Staphylococcal Chromosomal Cassette mec Composite Island with Significant Homology to Staphylococcus epidermidis ACME type II in Methicillin-Resistant Staphylococcus aureus Genotype ST22-MRSA-IV.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2011-02-22

    The arginine catabolic mobile element (ACME) is prevalent among ST8-MRSA-IVa (USA300) isolates and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME-positive, all were either MRSA genotype ST8-MRSA-IVa (7\\/23, 30%) or ST22-MRSA-IV (16\\/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and SCCmec composite island (ACME\\/SCCmec-CI) in ST22-MRSA-IVh isolates (n = 15). This ACME\\/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II in S. epidermidis ATCC 12228, a truncated copy of the J1 region of SCCmec I and a complete SCCmec IVh element. The composite island has a novel genetic organization with ACME located within orfX and SCCmec located downstream of ACME. One pvl-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmec IVa as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.

  7. Characterization of a novel arginine catabolic mobile element (ACME) and staphylococcal chromosomal cassette mec composite island with significant homology to Staphylococcus epidermidis ACME type II in methicillin-resistant Staphylococcus aureus genotype ST22-MRSA-IV.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2011-05-01

    The arginine catabolic mobile element (ACME) is prevalent among methicillin-resistant Staphylococcus aureus (MRSA) isolates of sequence type 8 (ST8) and staphylococcal chromosomal cassette mec (SCCmec) type IVa (USA300) (ST8-MRSA-IVa isolates), and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME positive, and all were either MRSA genotype ST8-MRSA-IVa (7\\/23, 30%) or MRSA genotype ST22-MRSA-IV (16\\/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and staphylococcal chromosomal cassette mec (SCCmec) composite island (ACME\\/SCCmec-CI) in ST22-MRSA-IVh isolates (n=15). This ACME\\/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II in S. epidermidis ATCC 12228, a truncated copy of the J1 region of SCCmec type I, and a complete SCCmec type IVh element. The composite island has a novel genetic organization, with ACME located within orfX and SCCmec located downstream of ACME. One PVL locus-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmec type IVa, as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.

  8. A new arginine-based dental adhesive system: formulation, mechanical and anti-caries properties.

    Science.gov (United States)

    Geraldeli, Saulo; Soares, Eveline F; Alvarez, Andres J; Farivar, Tanaz; Shields, Robert C; Sinhoreti, Mario A C; Nascimento, Marcelle M

    2017-08-01

    Secondary caries at the margins of composite restorations has been attributed to adhesive failure and consequent accumulation of cariogenic biofilms. To develop and evaluate an etch-and-rinse adhesive system containing arginine for sustainable release and recharge without affecting its mechanical properties. Arginine metabolism by oral bacteria generates ammonia, which neutralizes glycolytic acids and creates a neutral environmental pH that is less favorable to the growth of caries pathogens, thus reducing the caries risk at the tooth-composite interface. Experimental adhesives were formulated with methacrylate monomers and arginine at 5%, 7%, and 10% or no arginine (control). Adhesives were tested for: (i) mechanical properties of true stress (FS and UTS), modulus of elasticity (E), degree of conversion (DC), Knoop hardness number (KHN) and dentin microtensile bond strength (μ-TBS), (ii) arginine release and recharge, and (iii) antibacterial activities. Data was analyzed by t-test, one-way ANOVA and Tukey's tests. FS and UTS results showed no statistically significant differences between the 7% arginine-adhesive and control, while the results for E, DC, KHN and μ-TBS showed no difference among all groups. The 7% arginine-adhesive showed a high release rate of arginine (75.0μmol/cm 2 ) at 2h, and a more sustainable, controlled release rate (up to 0.2μmol/cm 2 ) at 30days. Incorporation of 7% arginine did not affect the physical and mechanical properties of the adhesive. Arginine was released from the adhesive at a rate and concentration that exhibited antibacterial effects, regardless of shifts in biofilm conditions such as sugar availability and pH. Secondary caries is recognized as the main reason for failure of dental restorations. The development of an arginine-based adhesive system has the potential to dramatically reduce the incidence and severity of secondary caries in adhesive restorations in a very economical fashion. Copyright © 2017 Elsevier Ltd

  9. Biomarkers of arginine and lysine excess.

    Science.gov (United States)

    Luiking, Yvette C; Deutz, Nicolaas E P

    2007-06-01

    Arginine supplementation is used in several disease states. In arginine-deficient states, supplementation is a logical choice of therapy. However, the definition of an arginine-deficient state is complex. For example, plasma arginine levels could be within normal range but intracellular arginine levels could be reduced because of membrane transport problems. Lysine competes with arginine for transport into the cell. In these situations, arginine supplementation of higher than required levels is proposed. Arginine has several important functions in metabolism as it is a precursor of metabolically active components such as nitric oxide (NO), ornithine, creatine, and polyamines. Supplementing arginine in excess could potentially overstimulate metabolism via enhanced production of NO. NO is a reactive component that, via production of radicals, will inactivate proteins. NO is also a powerful vasodilator, which could lead to severe hemodynamic instability. A good marker for excess supplementation of arginine or lysine could be an increased or reduced production rate of NO. However, NO production is difficult to measure because NO is a very labile component and is rapidly oxidized in blood. Stable isotope-labeled arginine and citrulline are used to trace the arginine-NO route. During supplementation of arginine in septic pigs or patients in septic shock, NO production, measured with stable isotope technology, is enhanced.

  10. Regulation of Arginine-Ornithine Exchange and the Arginine Deiminase Pathway in Streptococcus lactis

    NARCIS (Netherlands)

    POOLMAN, B; DRIESSEN, AJM; KONINGS, WN

    1987-01-01

    Streptococcus lactis metabolizes arginine by the argiqine deiminase (ADI) pathway. Resting cells of S. lactis grown in the presence of galactose and arginine maintain a high intracellular ornithine pool in the absence of arginine and other exogenous energy sources. Addition of arginine results in a

  11. Arginine homeostasis in allergic asthma

    NARCIS (Netherlands)

    Maarsingh, Harm; Zaagsma, Johan; Meurs, Herman

    2008-01-01

    Allergic asthma is a chronic disease characterized by early and late asthmatic reactions, airway hyperresponsiveness, airway inflammation and airway remodelling. Changes in L-arginine homeostasis may contribute to all these features of asthma by decreased nitric oxide (NO) production and increased

  12. L-Arginine in the treatment of valproate overdose - five clinical cases.

    Science.gov (United States)

    Schrettl, Verena; Felgenhauer, Norbert; Rabe, Christian; Fernando, Malkanthi; Eyer, Florian

    2017-04-01

    Valproic acid and its metabolites - particularly valproyl-CoA - are inhibitors of the enzyme N-acetylglutamate synthetase. The amino acid l-arginine can stimulate N-acetylglutamate synthetase activity and could be potentially used therapeutically to correct hyperammonemia caused by valproate therapy or overdose. Severely valproic-acid-poisoned patients are usually treated with l-carnitine or hemodialysis in order to decrease hyperammonemia. We herein report of five cases, in which l-arginine was administered. Observational study on five cases. Patients with hyperammonemia (i.e., ammonia 80 > μg/dL) and symptoms consistent with valproate overdose (i.e., drowsiness, coma) were selected for treatment with l-arginine. Data was collected retrospectively. l-Arginine decreased ammonia levels in a close temporal relation (case I ammonia in EDTA-plasma [μg/dL] decreased from 381 to 39; case II from 281 to 50; case III from 669 to 74; case IV from 447 to 56; case V from 202 to 60). In cases I and II, hemodialysis was performed and l-carnitine was given before the administration of l-arginine. In case III, hemodialysis was performed after the administration of l-arginine was already started. In cases IV and V, treatment with l-arginine was the sole measure to decrease ammonia levels in plasma. The results suggest that l-arginine may be beneficial in selected cases of valproate overdose complicated by hyperammonemia. l-Arginine could extend our conventional treatment options for valproic acid overdose.

  13. L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

    Science.gov (United States)

    Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2016-03-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P l-arginine, was reduced (P l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

  14. Physiological implications of arginine metabolism in plants

    Directory of Open Access Journals (Sweden)

    Gudrun eWinter

    2015-07-01

    Full Text Available Nitrogen is a limiting resource for plant growth in most terrestrial habitats since large amounts of nitrogen are needed to synthesize nucleic acids and proteins. Among the 21 proteinogenic amino acids, arginine has the highest nitrogen to carbon ratio, which makes it especially suitable as a storage form of organic nitrogen. Synthesis in chloroplasts via ornithine is apparently the only operational pathway to provide arginine in plants, and the rate of arginine synthesis is tightly regulated by various feedback mechanisms in accordance with the overall nutritional status. While several steps of arginine biosynthesis still remain poorly characterized in plants, much wider attention has been paid to inter- and intracellular arginine transport as well as arginine-derived metabolites. A role of arginine as alternative source besides glutamate for proline biosynthesis is still discussed controversially and may be prevented by differential subcellular localization of enzymes. Apparently, arginine is a precursor for nitric oxide (NO, although the molecular mechanism of NO production from arginine remains unclear in higher plants. In contrast, conversion of arginine to polyamines is well documented, and in several plant species also ornithine can serve as a precursor for polyamines. Both NO and polyamines play crucial roles in regulating developmental processes as well as responses to biotic and abiotic stress. It is thus conceivable that arginine catabolism serves on the one hand to mobilize nitrogen storages, while on the other hand it may be used to fine-tune development and defense mechanisms against stress. This review summarizes the recent advances in our knowledge about arginine metabolism, with a special focus on the model plant Arabidopsis thaliana, and pinpoints still unresolved critical questions.

  15. Convergent evolution of the arginine deiminase pathway : the ArcD and ArcE arginine/ornithine exchangers

    NARCIS (Netherlands)

    Noens, Elke E E; Lolkema, Juke S

    2016-01-01

    The arginine deiminase (ADI) pathway converts L-arginine into L-ornithine and yields 1 mol of ATP per mol of L-arginine consumed. The L-arginine/L-ornithine exchanger in the pathway takes up L-arginine and excretes L-ornithine from the cytoplasm. Analysis of the genomes of 1281 bacterial species

  16. L-arginine biosensors: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Neelam Verma

    2017-12-01

    Full Text Available Arginine has been considered as the most potent nutraceutics discovered ever, due to its powerful healing property, and it's been known to scientists as the Miracle Molecule. Arginine detection in fermented food products is necessary because, high level of arginine in foods forms ethyl carbamate (EC during the fermentation process. Therefore, L-arginine detection in fermented food products is very important as a control measure for quality of fermented foods, food supplements and beverages including wine. In clinical analysis arginine detection is important due to their enormous inherent versatility in various metabolic pathways, topmost in the synthesis of Nitric oxide (NO and tumor growth. A number of methods are being used for arginine detection, but biosensors technique holds prime position due to rapid response, high sensitivity and high specificity. However, there are many problems still to be addressed, including selectivity, real time analysis and interference of urea presence in the sample. In the present review we aim to emphasize the significant role of arginine in human physiology and foods. A small attempt has been made to discuss the various techniques used for development of arginine biosensor and how these techniques affect their performance. The choice of transducers for arginine biosensor ranges from optical, pH sensing, ammonia gas sensing, ammonium ion-selective, conductometric and amperometric electrodes because ammonia is formed as a final product.

  17. Arginine requirement and apparent absence of a lysine-arginine antagonist in fingerling channel catfish.

    Science.gov (United States)

    Robinson, E H; Wilson, R P; Poe, W E

    1981-01-01

    A series of growth studies, utilizing casein-gelatin based diets supplemented with crystalline amino acids, were conducted to determine the arginine requirement for fingerling channel catfish (Ictalurus punctatus) and to evaluate the effects of excessive levels of dietary lysine and arginine. Weight gain and feed efficiency data indicate the arginine requirement to be 1.03 +/- 0.07% and 1.00 +/- 0.06% of the dry diet, respectively. Based on growth this corresponds to 4.29% of the dietary protein. There was no evidence of an arginine-lysine antagonism when excess lysine was fed in diets adequate or marginal in arginine. Similarly, growth and feed efficiency data suggest the lack of an antagonism when excess arginine is added to diets marginal in lysine. Apparently channel catfish are not as sensitive to disproportionate lysine and arginine levels as are other animals.

  18. Regulatory roles for L-arginine in reducing white adipose tissue

    Science.gov (United States)

    Tan, Bi’e; Li, Xinguo; Yin, Yulong; Wu, Zhenlong; Liu, Chuang; Tekwe, Carmen D.; Wu, Guoyao

    2012-01-01

    As the nitrogenous precursor of nitric oxide, L-arginine regulates multiple metabolic pathways involved in the metabolism of fatty acids, glucose, amino acids, and proteins through cell signaling and gene expression. Specifically, arginine stimulates lipolysis and the expression of key genes responsible for activation of fatty acid oxidation to CO2 and water. The underlying mechanisms involve increases in the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), mitochondrial biogenesis, and the growth of brown adipose tissue growth. Furthermore, arginine regulates adipocyte-muscle crosstalk and energy partitioning via the secretion of cytokines and hormones. In addition, arginine enhances AMP-activated protein kinase (AMPK) expression and activity, thereby modulating lipid metabolism and energy balance toward the loss of triacylglycerols. Growing evidence shows that dietary supplementation with arginine effectively reduces white adipose tissue in Zucker diabetic fatty rats, diet-induced obese rats, growing-finishing pigs, and obese patients with type II diabetes. Thus, arginine can be used to prevent and treat adiposity and the associated metabolic syndrome. PMID:22652774

  19. Effects of L-arginine on intestinal development and endogenous ...

    African Journals Online (AJOL)

    Jane

    2011-08-01

    Aug 1, 2011 ... the underlying mechanism includes dietary L-arginine supplementation which regulated the productions of intestinal polyamine in jejunum, and stimulated endogenous arginine-synthesizing enzymes in neonatal piglets. Key words: Neonatal pig, L-arginine, intestinal development, arginine-synthetases.

  20. PRMT5: A novel regulator of Hepatitis B virus replication and an arginine methylase of HBV core.

    Directory of Open Access Journals (Sweden)

    Barbora Lubyova

    Full Text Available In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II enzyme responsible for the majority of symmetric dimethylarginine formation in polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV replication through epigenetic repression of HBV DNA transcription and interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5 interacts with the HBV core (HBc protein and dimethylates arginine residues within the arginine-rich domain (ARD of the carboxyl-terminus. ARD consists of four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis of ARDs revealed that arginine methylation of HBc required the wild-type status of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple potential ubiquitination, methylation and phosphorylation sites, out of which lysine K7 and arginines R150 (within ARDI and R156 (outside ARDs were shown to be modified by ubiquitination and methylation, respectively. The HBc symmetric dimethylation appeared to be linked to serine phosphorylation and nuclear import of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm. Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei of transfected cells. In summary, we identified PRMT5 as a potent controller of HBc cell trafficking and function and described two novel types of HBc post-translational modifications (PTMs, arginine methylation and ubiquitination.

  1. THE ARGININE AND PREARGININE GROUPS IN EDESTIN.

    Science.gov (United States)

    Simms, H S

    1930-09-20

    The author corroborates the data of Schmidt showing that the dissociation index of the third group of arginine is pK(3)' = 12.5. New titration data of edestin have been obtained in very alkaline solutions and show that there is a corresponding group with a titration index of pG' = 12.0, but present in much less quantity than can account for the arginine found on hydrolysis. The data support the theory that the combination of strong base or strong acid with proteins is produced by the formation of salts with the "extra groups" of those trivalent amino acids which can be isolated from the protein, with the exception of arginine. Arginine contributes to the titration curve in much smaller amount than is found on hydrolysis. This deficiency in the arginine group may be accounted for by the basic group in proteins having a titration index of pG' = 3.8 to 4.6 (depending on the protein), which apparently yields arginine on hydrolysis, and may properly be called prearginine.

  2. Symmetric allosteric mechanism of hexameric Escherichia coli arginine repressor exploits competition between L-arginine ligands and resident arginine residues.

    Directory of Open Access Journals (Sweden)

    Rebecca Strawn

    2010-06-01

    Full Text Available An elegantly simple and probably ancient molecular mechanism of allostery is described for the Escherichia coli arginine repressor ArgR, the master feedback regulator of transcription in L-arginine metabolism. Molecular dynamics simulations with ArgRC, the hexameric domain that binds L-arginine with negative cooperativity, reveal that conserved arginine and aspartate residues in each ligand-binding pocket promote rotational oscillation of apoArgRC trimers by engagement and release of hydrogen-bonded salt bridges. Binding of exogenous L-arginine displaces resident arginine residues and arrests oscillation, shifting the equilibrium quaternary ensemble and promoting motions that maintain the configurational entropy of the system. A single L-arg ligand is necessary and sufficient to arrest oscillation, and enables formation of a cooperative hydrogen-bond network at the subunit interface. The results are used to construct a free-energy reaction coordinate that accounts for the negative cooperativity and distinctive thermodynamic signature of L-arginine binding detected by calorimetry. The symmetry of the hexamer is maintained as each ligand binds, despite the conceptual asymmetry of partially-liganded states. The results thus offer the first opportunity to describe in structural and thermodynamic terms the symmetric relaxed state predicted by the concerted allostery model of Monod, Wyman, and Changeux, revealing that this state is achieved by exploiting the dynamics of the assembly and the distributed nature of its cohesive free energy. The ArgR example reveals that symmetry can be maintained even when binding sites fill sequentially due to negative cooperativity, which was not anticipated by the Monod, Wyman, and Changeux model. The molecular mechanism identified here neither specifies nor requires a pathway for transmission of the allosteric signal through the protein, and it suggests the possibility that binding of free amino acids was an early

  3. Dietary arginine supplementation speeds pulmonary VO2 kinetics during cycle exercise.

    Science.gov (United States)

    Koppo, Katrien; Taes, Youri E; Pottier, Andries; Boone, Jan; Bouckaert, Jacques; Derave, Wim

    2009-08-01

    To test the hypothesis that L-arginine (the substrate for nitric oxide synthase [NOS]) administration slows the VO2 kinetics at the onset of moderate-intensity exercise in humans. Seven physically active males were randomly assigned to receive either placebo (lactose) or L-arginine hydrochloride capsules (7.2 g x d(-1)) for 14 d in a double-blind crossover design, with a 7-d washout period between the two conditions. On day 11 and day 14 of each condition, the subjects completed two consecutive 6-min bouts of cycle exercise at 80% of the ventilatory threshold with a 12-min rest interval. VO2 was measured on a breath-by-breath basis, and VO2 kinetics were determined with a single exponential model from the averaged data derived from four repetitions. Capillary and venous blood samples were taken to determine plasma [La] and serum [arginine], respectively. There were no differences in circulating lactate either before or during exercise. However, serum [arginine] was higher (P L-arginine administration speeds the phase II pulmonary VO2 response by 12% at the onset of moderate-intensity exercise in humans.

  4. IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

    Directory of Open Access Journals (Sweden)

    E. A. Starikova

    2015-01-01

    Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

  5. Arginine and Lysine Transporters Are Essential for Trypanosoma brucei.

    OpenAIRE

    Mathieu, Christoph; Pereira de Macêdo, Juan; Hürlimann, Daniel; Wirdnam, Corina; Haindrich, Alexander; Suter, Marianne; González Salgado, Amaia; Schmidt, Remo; Inbar, Ehud; Mäser, Pascal; Bütikofer, Peter; Zilberstein, Dan; Rentsch, Doris

    2017-01-01

    For Trypanosoma brucei arginine and lysine are essential amino acids and therefore have to be imported from the host. Heterologous expression in Saccharomyces cerevisiae mutants identified cationic amino acid transporters among members of the T. brucei AAAP (amino acid/auxin permease) family. TbAAT5-3 showed high affinity arginine uptake (K m 3.6 ? 0.4 ?M) and high selectivity for L-arginine. L-arginine transport was reduced by a 10-times excess of L-arginine, homo-arginine, canavanine or arg...

  6. Arginine Adjunctive Therapy in Active Tuberculosis

    Directory of Open Access Journals (Sweden)

    Aliasghar Farazi

    2015-01-01

    Full Text Available Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18. Results. Arginine supplementation reduced constitutional symptoms (P=0.032 in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment (P=0.032 and P=0.04 and a reduced CRP at the end of the first month of treatment (P=0.03 versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2.

  7. Arginine methylation regulates the p53 response

    DEFF Research Database (Denmark)

    Jansson, Martin; Durant, Stephen T; Cho, Er-Chieh

    2008-01-01

    Activation of the p53 tumour suppressor protein in response to DNA damage leads to apoptosis or cell-cycle arrest. Enzymatic modifications are widely believed to affect and regulate p53 activity. We describe here a level of post-translational control that has an important functional consequence...... on the p53 response. We show that the protein arginine methyltransferase (PRMT) 5, as a co-factor in a DNA damage responsive co-activator complex that interacts with p53, is responsible for methylating p53. Arginine methylation is regulated during the p53 response and affects the target gene specificity...... of p53. Furthermore, PRMT5 depletion triggers p53-dependent apoptosis. Thus, methylation on arginine residues is an underlying mechanism of control during the p53 response....

  8. Effect of three different doses of arginine enhanced enteral nutrition on nutritional status and outcomes in well nourished postsurgical cancer patients: a randomized single blinded prospective trial.

    Science.gov (United States)

    De Luis, D A; Izaola, O; Terroba, M C; Cuellar, L; Ventosa, M; Martin, T

    2015-01-01

    Patients with head and neck cancer undergoing surgery have a high occurrence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients, using an enhanced enteral formula with three different doses of arginine could improve nutritional variables as well as clinical outcome, depending of arginine dose. A population of 84 patients with oral and laryngeal cancer was enrolled. At surgery patients were randomly assigned to three different treatment groups, each one containing at less 28 patients. Group I (28 patients) received an enteral diet supplements with a low physiological dose of arginine (5.7 g per day), group II (28 patients) received an isocaloric, isonitrogenous enteral formula with a medium dose of arginine (12.3 g per day) and group III (28 patients) received an isocaloric, isonitrogenous enteral formula with a high dose of arginine (18.9 g per day). The length of postoperative stay had a trend to be better with high dose of arginine received (31.9 ± 17.2 days in group I vs 27.8 ± 15.2 days in group II vs 24.8 ± 18.3 days in group III: p = 0.034). No differences were detected in postoperative infections complications and diarrhea. Fistula was less frequent in groups II and III than I (10.7% group I vs 3.6% group II vs 3.6% group III: p = 0.033), The length of postoperative stay had a trend to be better with high dose of arginine received (31.9 ± 17.2 days in group I vs 27.8 ± 15.2 days in group II vs 24.8 ± 18.3 days in group III: p = 0.034). Our results suggest that these patients could benefit from a high dose of arginine enhanced enteral formula to decrease length of hospital stay and fistula wound complications.

  9. Mapping arginine methylation in the human body and cardiac disease.

    Science.gov (United States)

    Onwuli, Donatus O; Rigau-Roca, Laura; Cawthorne, Chris; Beltran-Alvarez, Pedro

    2017-01-01

    Arginine methylation (ArgMe) is one of the most ubiquitous PTMs, and hundreds of proteins undergo ArgMe in, for example, brain. However, the scope of ArgMe in many tissues, including the heart, is currently underexplored. Here, we aimed to (i) identify proteins undergoing ArgMe in human organs, and (ii) expose the relevance of ArgMe in cardiac disease. The publicly available proteomic data is used to search for ArgMe in 13 human tissues. To induce H9c2 cardiac-like cell hypertrophy glucose is used. The results show that ArgMe is mainly tissue-specific; nevertheless, the authors suggest an embryonic origin of core ArgMe events. In the heart, 103 mostly novel ArgMe sites in 58 nonhistone proteins are found. The authors provide compelling evidence that cardiac protein ArgMe is relevant to cardiomyocyte ontology, and important for proper cardiac function. This is highlighted by the fact that genetic mutations affecting methylated arginine positions are often associated with cardiac disease, including hypertrophic cardiomyopathy. The pilot experimental data suggesting significant changes in ArgMe profiles of H9c2 cells upon induction of cell hypertrophy using glucose is provided. The work calls for in-depth investigation of ArgMe in normal and diseased tissues using methods including clinical proteomics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effects of Arginine Supplementation on Amino Acid Profiles in Blood and Tissues in Fed and Overnight-Fasted Rats

    Directory of Open Access Journals (Sweden)

    Milan Holecek

    2016-04-01

    Full Text Available Chronic arginine intake is believed to have favorable effects on the body. However, it might be hypothesized that excessive consumption of an individual amino acid exerts adverse effects on distribution and metabolism of other amino acids. We evaluated the effect of chronic intake of arginine on amino acid concentrations in blood plasma, liver, kidneys, and soleus and extensor digitorum longus muscles. Rats were fed a standard diet or a high-arginine diet (HAD for two months. Half of the animals in each group were sacrificed in the fed state, and the other half after fasting overnight. HAD increased blood plasma concentrations of urea, creatinine, arginine, and ornithine and decreased most other amino acids. Arginine and ornithine also increased in muscles and kidneys; an increase of lysine was observed in both muscle types. Methionine, phenylalanine, threonine, asparagine, glycine, serine, and taurine decreased in most tissues of HAD fed animals. Most of the effects of HAD disappeared after overnight fasting. It is concluded that (i enhanced dietary arginine intake alters distribution of almost all amino acids; and (ii to attain a better assessment of the effects of various nutritional interventions, an appropriate number of biochemical measurements must be performed in both postprandial and postabsorptive states.

  11. [L-arginine and male infertility].

    Science.gov (United States)

    Scibona, M; Meschini, P; Capparelli, S; Pecori, C; Rossi, P; Menchini Fabris, G F

    1994-12-01

    The clinical efficacy and acceptance of L-arginina HCL was tested in 40 infertile men. All of these men had a normal number of spermatozoa (> 20 million/ml), but a decreased motility; this decreased motility was not due to infection or to immunological disorders. The treatment consisted of 80 ml of 10% L-arginine HCL administered daily per os for 6 months. L-arginine HCL showed to be able to improve the motility of spermatozoa without any side-effects.

  12. 3-Nitropropionic Acid is a Suicide Inhibitor of MitochondrialRespiration that, Upon Oxidation by Complex II, Forms a Covalent AdductWith a Catalytic Base Arginine in the Active Site of the Enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-shar; Sun, Gang; Cobessi, David; Wang, Andy C.; Shen,John T.; Tung, Eric Y.; Anderson, Vernon E.; Berry, Edward A.

    2005-12-01

    We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. 1.3.5.1) at up to 2.1 {angstrom} resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg297 as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg297. The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg 297 to be increased by 83 Da and to have potential of losing 44 Da, consistent with decarboxylation, during fragmentation.

  13. Arginine and Citrulline and the Immune Response in Sepsis

    Science.gov (United States)

    Wijnands, Karolina A.P.; Castermans, Tessy M.R.; Hommen, Merel P.J.; Meesters, Dennis M.; Poeze, Martijn

    2015-01-01

    Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO) and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target. PMID:25699985

  14. Arginine and Citrulline and the Immune Response in Sepsis

    Directory of Open Access Journals (Sweden)

    Karolina A.P. Wijnands

    2015-02-01

    Full Text Available Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target.

  15. Effects of L-arginine on intestinal development and endogenous ...

    African Journals Online (AJOL)

    Arginine and its metabolites (citrulline and ornithine) were elevated, additionally, dietary supplementation with 0.8% L-arginine markedly enhanced jejunal villus height, villus area on day 11 and D-xylose absorption rate on day 19. Dietary supplementation with 0.8% L-arginine increased (P<0.05) activities of maltose and ...

  16. Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture

    DEFF Research Database (Denmark)

    Staalsø, Jonatan Myrup; Bergström, Anita; Edsen, Troels

    2013-01-01

    Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine...

  17. L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.

    Science.gov (United States)

    de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F

    2011-05-01

    Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.

  18. Lysine and arginine requirements of Salminus brasiliensis

    Directory of Open Access Journals (Sweden)

    Jony Koji Dairiki

    2013-08-01

    Full Text Available The objective of this work was to determine the dietary lysine (DL and dietary arginine (DA requirements of dourado (Salminus brasiliensis, through dose-response trials using the amino acid profiles of whole carcasses as a reference. Two experiments were carried out in a completely randomized design (n=4. In the first experiment, groups of 12 feed-conditioned dourado juveniles (11.4±0.2 g were stocked in 60 L cages placed in 300 L plastic indoor tanks in a closed circulation system. Fish were fed for 60 days on diets containing 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 % dietary lysine. In the second experiment, dourado juveniles (27.0±0.8 g were fed for 60 days on semipurified diets containing arginine at 1.0, 1.5, 2.0, 2.5 or 3.0%, in similar conditions to those of the first experiment. Optimal DL requirements, as determined by broken-line analysis method for final weight, weight gain and specific growth rate, were 2.15% DL or 5% lysine in dietary protein, and 1.48% DA or 3.43% arginine in dietary protein. The best feed conversion ratio is attained with 2.5% DL or 5.8% lysine in dietary protein and 1.4% DA or 3.25% arginine in dietary protein.

  19. Estimation of Plasma Arginine Vasopressin Concentration Using ...

    African Journals Online (AJOL)

    The purpose of this study was to estimate plasma arginine vasopressin (PAVP) using thirst perception (TP) and plasma osmolality (POSM) values before and at 60 minutes in control or euhydrate (group A, 0.0 ml/kg body weight of distilled water), hydrated (group B, 7.1ml/kg body weight of distilled water) and dehydrated ...

  20. Butyroyl-arginine as a potent virus inactivation agent.

    Science.gov (United States)

    Katsuyama, Yukiko; Yamasaki, Hisashi; Tsujimoto, Kazuko; Koyama, A Hajime; Ejima, Daisuke; Arakawa, Tsutomu

    2008-09-01

    Virus inactivation is a critical step in the manufacturing of recombinant therapeutic proteins, in particular antibodies, using mammalian expression systems. We have shown in the previous paper that arginine is effective in inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus at low temperature under mildly acidic pH, i.e., above pH 4.0; above this pH, conformational changes of most antibodies are negligible. We have here extended virus inactivation study of arginine to other enveloped viruses, such as Sendai virus and Newcastle Disease Virus (NDV), and observed that arginine was ineffective against both viruses under the similar conditions, i.e., on ice and above pH 4.0. However, an arginine derivative, butyroyl-arginine, showed a strong virucidal potency against Sendai virus, leading to a 4log reduction in virus yield at pH 4.0, but not against NDV. In addition, although arginine and butyroyl-arginine were equally effective against influenza virus having a cleaved form of hemagglutinin spike proteins, only butyroyl-arginine was significantly effective against the same virus, but having an uncleaved hemagglutinin spike proteins. Furthermore, butyroyl-arginine was more effective than arginine against HSV-1 at pH 4.5; i.e., it has a broader pH spectrum than does arginine.

  1. Chemical modification of arginine residues in the lactose repressor

    International Nuclear Information System (INIS)

    Whitson, P.A.; Matthews, K.S.

    1987-01-01

    The lactose repressor protein was chemically modified with 2,3-butanedione and phenylglyoxal. Arginine reaction was quantitated by either amino aced analysis or incorporation of 14 C-labeled phenylglyoxal. Inducer binding activity was unaffected by the modification of arginine residues, while both operator and nonspecific DNA binding activities were diminished, although to differing degrees. The correlation of the decrease in DNA binding activities with the modification of ∼ 1-2 equiv of arginine per monomer suggests increased reactivity of a functionally essential residue(s). For both reagents, operator DNA binding activity was protected by the presence of calf thymus DNA, and the extent of reaction with phenylglyoxal was simultaneously diminished. This protection presumably results from steric restriction of reagent access to an arginine(s) that is (are) essential for DNA binding interactions. These experiments suggest that there is (are) an essential reactive arginine(s) critical for repressor binding to DNA

  2. Effect of L-arginine supplementation on insulin resistance and adipocitokines levels in head and neck cancer non diabetic patients after surgery.

    Science.gov (United States)

    de Luis, Daniel; Izaola, Olatz; de la Fuente, Beatriz; Aller, R

    2014-10-10

    Previous studies have found that L-arginine induced beneficial effects over insulin resistance both in type 2 diabetes mellitus patients and healthy individuals. The aim of our study was to investigate whether an L-arginine enteral supplementation (20 g per day) in head and neck cancer patients could modify insulin resistance, leptin and adiponectin levels after surgery. At surgery 82 patients were randomly allocated to two groups: group I received an enteral diet supplements with a high dose of arginine (20g per day) and group II received an enteral formula without arginine. At basal time and on postoperative day 10, the following parameters were recorded: glucose, c-reactive protein, insulin, HOMA (homeostasis model assessment), leptin and adiponectin. Values of weight, body mass index, fat mass and fat free mass remained unchaged during the acute nutritional intervention in both groups. Insulin levels UI/L (-0.21+/-0.18) and HOMA units (-0.07+/-0.13) decreased in the arginine group. Adiponectin levels (+1.8+/-2.3ng/ml) increased in the arginine group. Short-term enteral L-arginine therapy addeded to usual enteral nutrition of patients affected by head and neck cancer and surgery without diabetes mellitus type 2 is able to improve insulin resistance and adiponectin levels. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  3. Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS

    Science.gov (United States)

    Elms, Shawn; Chen, Feng; Wang, Yusi; Qian, Jin; Askari, Bardia; Yu, Yanfang; Pandey, Deepesh; Iddings, Jennifer; Caldwell, Ruth B.

    2013-01-01

    Reduced production of nitric oxide (NO) is one of the first indications of endothelial dysfunction and precedes overt cardiovascular disease. Increased expression of Arginase has been proposed as a mechanism to account for diminished NO production. Arginases consume l-arginine, the substrate for endothelial nitric oxide synthase (eNOS), and l-arginine depletion is thought to competitively reduce eNOS-derived NO. However, this simple relationship is complicated by the paradox that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. One mechanism proposed to explain this is compartmentalization of intracellular l-arginine into distinct, poorly interchangeable pools. In the current study, we investigated this concept by targeting eNOS and Arginase to different intracellular locations within COS-7 cells and also BAEC. We found that supplemental l-arginine and l-citrulline dose-dependently increased NO production in a manner independent of the intracellular location of eNOS. Cytosolic arginase I and mitochondrial arginase II reduced eNOS activity equally regardless of where in the cell eNOS was expressed. Similarly, targeting arginase I to disparate regions of the cell did not differentially modify eNOS activity. Arginase-dependent suppression of eNOS activity was reversed by pharmacological inhibitors and absent in a catalytically inactive mutant. Arginase did not directly interact with eNOS, and the metabolic products of arginase or downstream enzymes did not contribute to eNOS inhibition. Cells expressing arginase had significantly lower levels of intracellular l-arginine and higher levels of ornithine. These results suggest that arginases inhibit eNOS activity by depletion of substrate and that the compartmentalization of l-arginine does not play a major role. PMID:23792682

  4. Early prevention by L-Arginine attenuates coronary atherosclerosis in a model of hypercholesterolemic animals; no positive results for treatment

    Directory of Open Access Journals (Sweden)

    Nematbakhsh Mehdi

    2009-03-01

    Full Text Available Abstract Background Endothelial dysfunction (ED is an independent predictor of cardiovascular events. ED is also a reversible disorder, and nitric oxide donors like L-arginine may promote this process. Despite the positive results from several studies, there are some studies that have shown that L-arginine administration did not improve endothelium-dependent dilation or the inflammatory state of patients. In this study the early and the late effects of L-arginine on coronary fatty streak formation and ED biomarkers were considered in hypercholesterolemic rabbits. Methods 36 white male rabbits randomly assigned in 3 groups. Rabbits were fed 1% high-cholesterol diet (LP group, n = 15, or high-cholesterol diet with oral L-arginine (3% in drinking water (EP group, n = 15 or standard diet (control group, n = 6 for 4 weeks (phase I. Afterward, all animals were fed normal diet for 4 weeks (phase II. In the second phase, L-arginine was discontinued for EP group and was begun for LP group. The plasma levels of lipids, von Willebrand factor (vWF, and nitrite were compared before and after 4 and 8 weeks of experiment. Coronary fatty streak formation was measure after 4 and 8 weeks of experiment. Results The plasma levels of lipids were increased significantly in both groups of LP and EP after phase I. The hypercholesterolemia induced significant increased vWF release in LP group. The L-arginine supplementation led to significant plasma nitrite increment in EP group. The vWF in LP group was higher than other groups (p Conclusion Early prevention by L-arginine may be helpful to prevent the ED, but our study did not suggest the treatment. It seems reasonable to consider ED-aside from control the cardiovascular risk factors in primary prevention of atherosclerosis and its clinical outcomes before development of irreversible vascular damage.

  5. Effects of arginine on multimodal anion exchange chromatography.

    Science.gov (United States)

    Hirano, Atsushi; Arakawa, Tsutomu; Kameda, Tomoshi

    2015-12-01

    The effects of arginine on binding and elution properties of a multimodal anion exchanger, Capto adhere, were examined using bovine serum albumin (BSA) and a monoclonal antibody against interleukin-8 (mAb-IL8). Negatively charged BSA was bound to the positively charged Capto adhere and was readily eluted from the column with a stepwise or gradient elution using 1M NaCl at pH 7.0. For heat-treated BSA, small oligomers and remaining monomers were also eluted using a NaCl gradient, whereas larger oligomers required arginine for effective elution. The positively charged mAb-IL8 was bound to Capto adhere at pH 7.0. Arginine was also more effective for elution of the bound mAb-IL8 than was NaCl. The results imply that arginine interacts with the positively charged Capto adhere. The mechanism underlying the interactions of arginine with Capto adhere was examined by calculating the binding free energy between an arginine molecule and a Capto adhere ligand in water through molecular dynamics simulations. The overall affinity of arginine for Capto adhere is attributed to the hydrophobic and π-π interactions between an arginine side chain and the aromatic moiety of the ligand as well as hydrogen bonding between arginine and the ligand hydroxyl group, which may account for the characteristics of protein elution using arginine. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Preparation of arginine (guanide 14C)

    International Nuclear Information System (INIS)

    Pichat, L.; Baret, C.

    1960-01-01

    Reaction of anhydrous ammoniac at 800 deg. C on 14 CO 3 Ba gives rise to barium cyanamide 14 C with a yield of about 98 per cent. Addition on H 2 S on cyanamide 14 C leads to thiourea 14 C with a 85 per cent yield, which is quantitatively transformed into S-ethyl-isothiouronium iodide by treatment with methyl iodide. This 14 C-isothiouronium salt is used to introduce 14 C guanide group in α-N-tosyl-ornithine; tosyl group in α-N-tosyl-arginine thus obtained is then removed by hydrolysis with hydrochloric acid. Arginine is separated as flavianic acid salt and is purified on exchange resin Dowex-50. The overall yield based on 14 CO 3 Ba is 25 per cent. (author) [fr

  7. Xenoestrogens regulate the activity of arginine methyltransferases.

    Science.gov (United States)

    Cheng, Donghang; Bedford, Mark T

    2011-01-24

    Arginine methylation is a common post-translational modification that has been strongly implicated in transcriptional regulation. The arginine methyltransferases (PRMTs) were first reported as transcriptional coactivators for the estrogen and androgen receptors. Compounds that inhibit these enzymes will provide us with valuable tools for dissecting the roles of these enzymes in cells, and will possibly also have therapeutic applications. In order to identify such inhibitors of the PRMTs, we have previously performed a high-throughput screen using a small molecule library. These compounds were named arginine methyltransferase inhibitors (AMIs). The majority of these inhibitors were polyphenols, and one in particular (AMI-18) shared additional features with a group of known xenoestrogens. We, thus, tested a panel of xenoestrogens and found that a number of them possess the ability to inhibit PRMT activity, in vitro. These inhibitors primarily target CARM1, and include licochalcone A, kepone, benzyl 4-hydroxybenzoate, and tamoxifen. We developed a cell-based reporter system for CARM1 activity, and showed that tamoxifen (IC(50) =30 μM) inhibits this PRMT. The ability of these compounds to regulate the activity of transcriptional coactivators may be an unappreciated mechanism of action for xenoestrogens, and might also explain the efficacy of high-dose tamoxifen treatment on estrogen receptor negative cancers. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Effect of L-arginine on the catalytic activity and stability of nickel nanoparticles for hydrolytic dehydrogenation of ammonia borane

    Science.gov (United States)

    Umegaki, Tetsuo; Xu, Qiang; Kojima, Yoshiyuki

    2012-10-01

    Amorphous nickel catalysts were synthesized by reducing the nickel(II) species in an aqueous NaBH4/NH3BH3 solution with and without L-arginine. The nickel catalyst with L-arginine maintains relatively high activity for hydrolysis of NH3BH3 to generate a stoichiometric amount of hydrogen with the cycle number up to 11 (827 mL s-1 (mol-Ni)-1 at the 11th cycle with L-arginine = 35 mg), while the reaction rate in the presence of the bare nickel catalyst was relatively low through the cycle number up to 11 (232 mL s-1 (mol-Ni)-1 at the 11th cycle). After catalytic reaction, the nickel catalyst with L-arginine possesses the high dispersion (diameters of nickel nanoparticles L-arginine maintains the dispersion of nickel nanoparticles (diameters of nickel nanoparticles <10 nm), leading to higher activity against cycle tests than the bare nickel catalyst.

  9. The role of arginine and arginine-metabolizing enzymes during Giardia – host cell interactions in vitro

    Science.gov (United States)

    2013-01-01

    Background Arginine is a conditionally essential amino acid important in growing individuals and under non-homeostatic conditions/disease. Many pathogens interfere with arginine-utilization in host cells, especially nitric oxide (NO) production, by changing the expression of host enzymes involved in arginine metabolism. Here we used human intestinal epithelial cells (IEC) and three different isolates of the protozoan parasite Giardia intestinalis to investigate the role of arginine and arginine-metabolizing enzymes during intestinal protozoan infections. Results RNA expression analyses of major arginine-metabolizing enzymes revealed the arginine-utilizing pathways in human IECs (differentiated Caco-2 cells) grown in vitro. Most genes were constant or down-regulated (e.g. arginase 1 and 2) upon interaction with Giardia, whereas inducible NO synthase (iNOS) and ornithine decarboxylase (ODC) were up-regulated within 6 h of infection. Giardia was shown to suppress cytokine-induced iNOS expression, thus the parasite has both iNOS inducing and suppressive activities. Giardial arginine consumption suppresses NO production and the NO-degrading parasite protein flavohemoglobin is up-regulated in response to host NO. In addition, the secreted, arginine-consuming giardial enzyme arginine deiminase (GiADI) actively reduces T-cell proliferation in vitro. Interestingly, the effects on NO production and T cell proliferation could be reversed by addition of external arginine or citrulline. Conclusions Giardia affects the host’s arginine metabolism on many different levels. Many of the effects can be reversed by addition of arginine or citrulline, which could be a beneficial supplement in oral rehydration therapy. PMID:24228819

  10. Effect of in ovo injection with L-arginine on productive and ...

    African Journals Online (AJOL)

    This study evaluated the influence of administering different levels of L-arginine into eggs of 0-day-old Japanese quail embryos. On day 0 of incubation, 480 eggs (120 for each treatment group) were injected with 0% arginine (C group), 1% arginine (T1), 2% arginine (T2) or 3% arginine (T3). After hatching, 336 quail chicks ...

  11. [Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris].

    Science.gov (United States)

    Sozykin, A V; Noeva, E A; Balakhonova, T V; Pogorelova, O A; Men'shikov, M Iu

    2000-01-01

    Examination of the action of donor NO (L-arginine) on platelet aggregation, endothelial function and exercise tolerance in patients with stable angina of effort (SAE). 42 patients with SAE (functional class I-II) and 10 healthy volunteers (control group) were assigned to two groups. 22 patients of group 1 were randomized to cross-over. They received cardiket (60 mg/day for 10 days or cardiket (60 mg/day) in combination with L-arginine (15 g/day for 10 days). 20 SAE patients of group 2 and control group received L-arginine (15 g/day for 10 days). In each group blood lipids were examined, and bicycle exercise test (BET) was performed. In addition, platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine. Compared to control group, endothelial function significantly improved in group 2 (from 5.0 +/- 2.9 to 7.8 +/- 4.1% vs 7.1 +/- 1.9 to 6.6 +/- 4.8%) (M +/- SD). BET duration increased in all the patients. After ADP addition in concentrations 1.5, 2.0, and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged. Positive effect of L-arginine on endothelial function, exercise tolerance and platelet aggregation was observed in patients with stable angina of effort (functional class I-II). Therefore, arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease.

  12. A comparison of DNA compaction by arginine and lysine peptides: A physical basis for arginine rich protamines

    OpenAIRE

    DeRouchey, Jason; Hoover, Brandon; Rau, Donald C

    2013-01-01

    Protamines are small, highly positively charged peptides used to package DNA to very high densities in sperm nuclei. Tight DNA packing is considered essential to minimize DNA damage by mutagens and reactive oxidizing species. A striking and general feature of protamines is the almost exclusive use of arginine over lysine for the positive charge to neutralize DNA. We have investigated whether this preference for arginine might arise from a difference in DNA condensation by arginine and lysine ...

  13. Influence of short-term L-arginine supplementation on carbohydrate balance in rats with ischemia-reperfusion syndrome.

    Science.gov (United States)

    Krauss, Hanna; Bogdański, Paweł; Sosnowski, Przemysław; Suliburska, Joanna; Jabłecka, Anna; Jastak, Rafał; Sassek, Maciej; Maćkowiak, Paweł; Cieślewicz, Artur; Pupek-Musialik, Danuta

    2012-01-01

    There are studies showing stimulative effect of arginine on insulin secretion. This mechanism is not fully explained. The effects of the impact of arginine on carbohydrate balance under the conditions of ischemia and reperfusion remain to be determined. The aim of this study is the evaluation of the influence of short-term L-arginine supplementation on the concentration of glucose and insulin in blood and insulin binding in rat skeletal muscle under the conditions of ischemia and reperfusion. The study was conducted on male Wistar rats with average body mass 250 ± 30 g. Animals were divided into four groups: Group I - control, Group II - placebo, Group III - L-arginine 500 mg/kg/24 h for 5 days, Group IV - L-arginine and L-NAME (75 μmol/rat/24 h) for 5 days. Each group was divided into subgroups depending on duration of ischemia and reperfusion. Acute ischemia of hind limb was induced in each group by putting pneumatic tourniquet on the thigh. Blood samples and skeletal muscles were collected from the rats. Plasma concentrations of glucose and insulin were measured. Insulin binding to insulin receptors was determined in skeletal muscle. A clear reduction of insulin binding to receptor was found in the group of animals without ischemia and the group supplemented with L-arginine and subjected to 4-h ischemia and 30- and 120-min reperfusion. A significant increase in insulin level was found in groups of animals with L-arginine and/or L-NAME subjected to 4-h ischemia at all times of reperfusion. Supplementation with L-arginine and/or L-NAME decreased levels of glucose in blood serum of animals undergoing ischemia-reperfusion syndrome compared to the control and placebo groups. Under conditions of ischemia-reperfusion, short-term administration of L-arginine causes a decrease in insulin binding capacity of insulin receptors in skeletal muscle, an increase in insulin level and a decrease in the concentration of glucose in blood serum.

  14. Effects of 7 days of arginine-alpha-ketoglutarate supplementation on blood flow, plasma L-arginine, nitric oxide metabolites, and asymmetric dimethyl arginine after resistance exercise.

    Science.gov (United States)

    Willoughby, Darryn S; Boucher, Tony; Reid, Jeremy; Skelton, Garson; Clark, Mandy

    2011-08-01

    Arginine-alpha-ketoglutarate (AAKG) supplements are alleged to increase nitric oxide production, thereby resulting in vasodilation during resistance exercise. This study sought to determine the effects of AAKG supplementation on hemodynamics and brachial-artery blood flow and the circulating levels of L-arginine, nitric oxide metabolites (NOx; nitrate/nitrite), asymmetric dimethyl arginine (ADMA), and L-arginine:ADMA ratio after resistance exercise. Twenty-four physically active men underwent 7 days of AAKG supplementation with 12 g/day of either NO(2) Platinum or placebo (PLC). Before and after supplementation, a resistance-exercise session involving the elbow flexors was performed involving 3 sets of 15 repetitions with 70-75% of 1-repetition maximum. Data were collected immediately before, immediately after (PST), and 30 min after (30PST) each exercise session. Data were analyzed with factorial ANOVA (p L-arginine was increased in the NO(2) group (p = .001). NOx was shown to increase in both groups at PST (p = .001) and at 30PST (p = .001) but was not different between groups. ADMA was not affected between tests (p = .26) or time points (p = .31); however, the L-arginine:ADMA ratio was increased in the NO(2) group (p = .03). NO(2) Platinum increased plasma L-arginine levels; however, the effects observed in hemodynamics, brachial-artery blood flow, and NOx can only be attributed to the resistance exercise.

  15. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    Science.gov (United States)

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  16. Effect of arginine deficiency on arginine-dependent post-translational protein modifications in mice

    NARCIS (Netherlands)

    Kwikkers, Karin L.; Ruijter, Jan M.; Labruyère, Wil T.; McMahon, Kathryn K.; Lamers, Wouter H.

    2005-01-01

    Transgenic mice that overexpress arginase-I in their small-intestinal enterocytes suffer from a pronounced, but selective decrease in circulating arginine levels during the suckling period, resulting in impaired growth and development of hair, muscle and immune system. In the present study, we

  17. Weissella halotolerans W22 combines arginine deiminase and ornithine decarboxylation pathways and converts arginine to putrescine

    NARCIS (Netherlands)

    Pereira, C. I.; San Romao, M. V.; Lolkema, J. S.; Barreto Crespo, M. T.; Baretto Crespo, M.

    2009-01-01

    Aims: To demonstrate that the meat food strain Weissella halotolerans combines an ornithine decarboxylation pathway and an arginine deiminase (ADI) pathway and is able to produce putrescine, a biogenic amine. Evidence is shown that these two pathways produce a proton motive force (PMF). Methods and

  18. Arginine and Lysine Transporters Are Essential for Trypanosoma brucei.

    Science.gov (United States)

    Mathieu, Christoph; Macêdo, Juan P; Hürlimann, Daniel; Wirdnam, Corina; Haindrich, Alexander C; Suter Grotemeyer, Marianne; González-Salgado, Amaia; Schmidt, Remo S; Inbar, Ehud; Mäser, Pascal; Bütikofer, Peter; Zilberstein, Dan; Rentsch, Doris

    2017-01-01

    For Trypanosoma brucei arginine and lysine are essential amino acids and therefore have to be imported from the host. Heterologous expression in Saccharomyces cerevisiae mutants identified cationic amino acid transporters among members of the T. brucei AAAP (amino acid/auxin permease) family. TbAAT5-3 showed high affinity arginine uptake (Km 3.6 ± 0.4 μM) and high selectivity for L-arginine. L-arginine transport was reduced by a 10-times excess of L-arginine, homo-arginine, canavanine or arginine-β-naphthylamide, while lysine was inhibitory only at 100-times excess, and histidine or ornithine did not reduce arginine uptake rates significantly. TbAAT16-1 is a high affinity (Km 4.3 ± 0.5 μM) and highly selective L-lysine transporter and of the compounds tested, only L-lysine and thialysine were competing for L-lysine uptake. TbAAT5-3 and TbAAT16-1 are expressed in both procyclic and bloodstream form T. brucei and cMyc-tagged proteins indicate localization at the plasma membrane. RNAi-mediated down-regulation of TbAAT5 and TbAAT16 in bloodstream form trypanosomes resulted in growth arrest, demonstrating that TbAAT5-mediated arginine and TbAAT16-mediated lysine transport are essential for T. brucei. Growth of induced RNAi lines could partially be rescued by supplementing a surplus of arginine or lysine, respectively, while addition of both amino acids was less efficient. Single and double RNAi lines indicate that additional low affinity uptake systems for arginine and lysine are present in T. brucei.

  19. Leishmania metacaspase: an arginine-specific peptidase.

    Science.gov (United States)

    Martin, Ricardo; Gonzalez, Iveth; Fasel, Nicolas

    2014-01-01

    The purpose of this chapter is to give insights into metacaspase of Leishmania protozoan parasites as arginine-specific cysteine peptidase. The physiological role of metacaspase in Leishmania is still a matter of debate, whereas its peptidase enzymatic activity has been well characterized. Among the different possible expression systems, metacaspase-deficient yeast cells (Δyca1) have been instrumental in studying the activity of Leishmania major metacaspase (LmjMCA). Here, we describe techniques for purification of LmjMCA and its activity measurement, providing a platform for further identification of LmjMCA substrates.

  20. Functional and neurochemical profile of place learning after L-nitro-arginine in the rat

    DEFF Research Database (Denmark)

    Mogensen, Jesper; Wörtwein, Gitta; Hasman, Andreas

    1995-01-01

    Neurobiology, nitrogenoxid (NO), place learning, rotte, L-Nitro-Arginin, funktionel genopretning......Neurobiology, nitrogenoxid (NO), place learning, rotte, L-Nitro-Arginin, funktionel genopretning...

  1. L-arginine induces relaxation of rat aorta possibly through non-endothelial nitric oxide formation.

    OpenAIRE

    Moritoki, H.; Ueda, H.; Yamamoto, T.; Hisayama, T.; Takeuchi, S.

    1991-01-01

    1. The relaxation of rings of rat thoracic aorta induced by L-arginine and its derivatives was investigated. 2. L-Arginine (0.3-100 microM), but not D-arginine, induced relaxation of the arteries, which was detectable after 2 h and maximal after 4-6 h on its repeated application; it was endothelium-independent. 3. L-Arginine methyl ester, N alpha-benzoyl L-arginine and L-homo-arginine had essentially similar effects to those of L-arginine. 4. NG-nitro L-arginine methyl ester (L-NAME, 3 microM...

  2. Nutritional consequences of interspecies differences in arginine and lysine metabolism.

    Science.gov (United States)

    Ball, Ronald O; Urschel, Kristine L; Pencharz, Paul B

    2007-06-01

    Differences in lysine and arginine requirements among various species such as omnivores (humans, pigs, rats, dogs), carnivores (cats), herbivores (rabbits, horses), ruminants (cattle), poultry, and fish, are covered in detail in this article. Although lysine is classified as an indispensable amino acid across species, the classification of arginine as either an indispensable or dispensable amino acid is more ambiguous because of differences among species in rates of de novo arginine synthesis. Because lysine is most often the limiting amino acid in the diet, its requirement has been extensively studied. By use of the ideal protein concept, the requirements of the other indispensable amino acids can be extrapolated from the lysine requirement. The successful use of this concept in pigs is compared with potential application of the ideal protein concept in humans. The current dietary arginine requirement varies widely among species, with ruminants, rabbits, and rats having relatively low requirements and carnivores, fish, and poultry having high requirements. Interspecies differences in metabolic arginine utilization and reasons for different rates of de novo arginine synthesis are reviewed in detail, as these are the primary determinants of the dietary arginine requirement. There is presently no dietary requirement for humans of any age, although this needs to be reassessed, particularly in neonates. A thorough understanding of the factors contributing to the lysine and arginine requirements in different species will be useful in our understanding of human amino acid requirements.

  3. L-Arginine Attenuates Diabetic Nephropathy In Streptozotocin ...

    African Journals Online (AJOL)

    ... renal activities of glutathione peroxidase(GPx),superoxide dismutase(SOD), LDH, aldose reductase(AR),sorbitol dehydrogenase(SDH), levels of renal glutathione(GSH) and NOx in the diabetic group treated with L-arginine. It can be concluded that L-arginine supplementation may become a promising solution to reduce ...

  4. The do's and don'ts of arginine supplementation

    African Journals Online (AJOL)

    properties, there has been increased effort in defining possible clinical uses for arginine.3. Furthermore, the ... endogenous daily production of 15–20 g occurs via the citrulline intestinal-renal axis.2. A large proportion .... sepsis, the endogenous synthesis of arginine from the amino acid citrulline, is reduced to one third of the ...

  5. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  6. Small Molecule Inhibitors of Protein Arginine Methyltransferases

    Science.gov (United States)

    Hu, Hao; Qian, Kun; Ho, Meng-Chiao; Zheng, Y. George

    2016-01-01

    Introduction Arginine methylation is an abundant posttranslational modification occurring in mammalian cells and catalyzed by protein arginine methyltransferases (PRMTs). Misregulation and aberrant expression of PRMTs are associated with various disease states, notably cancer. PRMTs are prominent therapeutic targets in drug discovery. Areas covered The authors provide an updated review of the research on the development of chemical modulators for PRMTs. Great efforts are seen in screening and designing potent and selective PRMT inhibitors, and a number of micromolar and submicromolar inhibitors have been obtained for key PRMT enzymes such as PRMT1, CARM1, and PRMT5. The authors provide a focus on their chemical structures, mechanism of action, and pharmacological activities. Pros and cons of each type of inhibitors are also discussed. Expert opinion Several key challenging issues exist in PRMT inhibitor discovery. Structural mechanisms of many PRMT inhibitors remain unclear. There lacks consistency in potency data due to divergence of assay methods and conditions. Physiologically relevant cellular assays are warranted. Substantial engagements are needed to investigate pharmacodynamics and pharmacokinetics of the new PRMT inhibitors in pertinent disease models. Discovery and evaluation of potent, isoform-selective, cell-permeable and in vivo-active PRMT modulators will continue to be an active arena of research in years ahead. PMID:26789238

  7. Structures of Bacterial Biosynthetic Arginine Decarboxylases

    Energy Technology Data Exchange (ETDEWEB)

    F Forouhar; S Lew; J Seetharaman; R Xiao; T Acton; G Montelione; L Tong

    2011-12-31

    Biosynthetic arginine decarboxylase (ADC; also known as SpeA) plays an important role in the biosynthesis of polyamines from arginine in bacteria and plants. SpeA is a pyridoxal-5'-phosphate (PLP)-dependent enzyme and shares weak sequence homology with several other PLP-dependent decarboxylases. Here, the crystal structure of PLP-bound SpeA from Campylobacter jejuni is reported at 3.0 {angstrom} resolution and that of Escherichia coli SpeA in complex with a sulfate ion is reported at 3.1 {angstrom} resolution. The structure of the SpeA monomer contains two large domains, an N-terminal TIM-barrel domain followed by a {beta}-sandwich domain, as well as two smaller helical domains. The TIM-barrel and {beta}-sandwich domains share structural homology with several other PLP-dependent decarboxylases, even though the sequence conservation among these enzymes is less than 25%. A similar tetramer is observed for both C. jejuni and E. coli SpeA, composed of two dimers of tightly associated monomers. The active site of SpeA is located at the interface of this dimer and is formed by residues from the TIM-barrel domain of one monomer and a highly conserved loop in the {beta}-sandwich domain of the other monomer. The PLP cofactor is recognized by hydrogen-bonding, {pi}-stacking and van der Waals interactions.

  8. Arginine specific aminopeptidase from Lactobacillus brevis

    Directory of Open Access Journals (Sweden)

    Arya Nandan

    2010-12-01

    Full Text Available The proteolytic system of lactic acid bacteria contribute to the development of flavor during the ripening of cheese through the generation of short peptides and free amino acids, which directly or indirectly act as flavor precursors. Newly isolated lactic acid bacteria (LAB as well as those procured from culture collection centers were screened for the production of various substrate specific aminopeptidases. Among all the strains screened, L. brevis (NRRL B-1836 was found to produce quantifiable amount of intracellular arginine specific aminopeptidase (EC 3.4.11.6. The productivity of arginine aminopeptidase in 5 L fermentor was 36 IU/L/h. The Luedeking and Piret model was tested for intracellular production of aminopeptidase and the data seemed to fit well, as the correlation coefficient was 0.9964 for MRS. The αAP and βAP was 0.4865 and 0.0046, respectively in MRS medium indicating that the yield was predominantly depended on growth. The culture produced lactic acid and also tolerated pH 2.0-3.0 and 0.3-0.5% bile salts, the most important probiotic features.

  9. Purification of free arginine from chickpea (Cicer arietinum) seeds.

    Science.gov (United States)

    Cortés-Giraldo, Isabel; Megías, Cristina; Alaiz, Manuel; Girón-Calle, Julio; Vioque, Javier

    2016-02-01

    Chickpea is a grain legume widely consumed in the Mediterranean region and other parts of the world. Chickpea seeds are rich in proteins but they also contain a substantial amount of free amino acids, especially arginine. Hence chickpea may represent a useful source of free amino acids for nutritional or pharmaceutical purposes. Arginine is receiving great attention in recent years because it is the substrate for the synthesis of nitric oxide, an important signaling molecule involved in numerous physiological and pathological processes in mammals. In this work we describe a simple procedure for the purification of arginine from chickpea seeds, using nanofiltration technology and an ion-exchange resin, Amberlite IR-120. Arginine was finally purified by precipitation or crystallization, yielding preparations with purities of 91% and 100%, respectively. Chickpea may represent an affordable green source of arginine, and a useful alternative to production by fermentation or protein hydrolysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Intricate Effects of α-Amino and Lysine Modifications on Arginine Methylation of the N-Terminal Tail of Histone H4.

    Science.gov (United States)

    Fulton, Melody D; Zhang, Jing; He, Maomao; Ho, Meng-Chiao; Zheng, Y George

    2017-07-18

    Chemical modifications of the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) of the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and >450 histone PTMs that have been discovered, and the PTMs of lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood. In this study, we investigated how naturally occurring N-terminal acetylation and PTMs of histone H4 lysine-5 (H4K5) affect arginine-3 methylation catalyzed by both type I and type II PRMTs at the biochemical level. Our studies found that acylations of H4K5 resulted in decreased levels of arginine methylation by PRMT1, PRMT3, and PRMT8. In contrast, PRMT5 exhibits an increased rate of arginine methylation upon H4K5 acetylation, propionylation, and crotonylation, but not upon H4K5 methylation, butyrylation, or 2-hydroxyisobutyrylation. Methylation of H4K5 did not affect arginine methylation by PRMT1 or PRMT5. There was a small increase in the rate of arginine methylation by PRMT8. Strikingly, a marked increase in the rate of arginine methylation was observed for PRMT3. Finally, N-terminal acetylation reduced the rate of arginine methylation by PRMT3 but had little influence on PRMT1, -5, and -8 activity. These results together highlight the underlying mechanistic differences in substrate recognition among different PRMTs and pave the way for the elucidation of the complex interplay of histone modifications.

  11. L-arginine supplementation and experimental airway hyperreactivity.

    Science.gov (United States)

    Antosova, M; Strapkova, A

    2013-01-01

    The interest in L-arginine metabolism was triggered primarily by the discovery of nitric oxide (NO) synthesis in mammals and its remarkable biological roles. The real role of L-arginine in the airway hyperreactivity (AHR) has not been established yet. Therefore, we studied whether supplementation of L-arginine can influence the experimental AHR evoked by two different triggers - allergen and exogenous irritant (toluene vapours). Male TRIK strain guinea pigs were used in the study. We used two patterns of pretreatment with L-arginine in vivo, short- and long-term, in a dose of 300 mg/kg administered i.p., after which we studied reactivity of airway smooth muscles in vitro. Pretreatment with L-arginine for 3 days decreased the airway smooth muscle reactivity induced by toluene vapour, whereas pretreatment for 17 days was without any additional effect on smooth muscle reactivity. The short-term pretreatment in ovalbumin-induced hyperreactivity caused an increase in airway smooth muscle reactivity to lower concentrations of both bronchoconstrictors. On the other side, this pretreatment significantly decreased smooth muscle reactivity to high concentrations of both bronchoconstrictors. Supplementation of L-arginine resulted in a modification of the airway smooth muscle response. The effect of supplementation was different depending on the AHR trigger, airway region and pretreatment duration. The results also underscore the importance of an optimal L-arginine level for the control of bronchial tone.

  12. Asymmetric Dimethyl Arginine in Hypothyroid Patients

    International Nuclear Information System (INIS)

    Abdel-Messeih, P.L.

    2012-01-01

    Thyroid diseases may lead to endothelial dysfunction, however, the mechanism underlying the endothelial dysfunction in thyroid disease is still not clear. Asymmetric dimethyl arginine (ADMA), a novel inhibitor of endothelial nitric oxide synthetase (eNOS), was reported to inhibit nitric oxide (NO) synthesis from L-arginine. The present study was carried out to investigate ADMA levels together with effects of dislipidemia in sub-clinical and overt hypothyroid females. There were significant increase in the levels of total cholesterol, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), thyroid stimulating hormone (TSH) and ADMA in hypothyroid females as compared to controls while the levels of NO and free T 4 were significantly decreased than controls. Sub-clinical hypothyroid females had significant high TSH, LDL-c and non-significantly high ADMA levels and total cholesterol as compared to controls while they had significant decrease in NO, HDL-c and non-significant decrease in free T 4 as compared to controls. There were significant negative correlations between NO and both ADMA (r 2 = 0.84) and free T 4 (r 2 = 0.95) in overt hypothyroid group while significant positive correlation (r 2 = 0.85) was detected between TSH and HDL-c in the same group. These results are highly suggestive that the decrease of nitric oxide secondary to accumulation of ADMA represent an important pathogenic factor together with dyslipidemia in endothelial dysfunction and increased cardiovascular risk especially in hypothyroid females

  13. Reduced caloric intake during endotoxemia reduces arginine availability and metabolism.

    Science.gov (United States)

    Poeze, Martijn; Bruins, Maaike J; Luiking, Yvette C; Deutz, Nicolaas E

    2010-04-01

    Inadequate caloric intake increases the risk of sepsis-induced complications. Metabolic changes during sepsis indicate that the availability of the amino acid l-arginine decreases. Availability of arginine may further decrease during reduced caloric intake, which thereby limits the adaptive response of arginine-nitric oxide metabolism during sepsis. We tested the hypothesis that reduced caloric intake during endotoxemia, as an experimental model for sepsis, further reduces arginine availability. In a randomized trial, a 7-d reduced caloric intake feed regimen (RE; n = 9) was compared with a normal control feed regimen (CE; n = 9), before 24 h of endotoxemia, as a model for sepsis. Whole-body arginine-nitric oxide metabolism and protein metabolism were measured by using a stable-isotope infusion of [(15)N(2)]arginine, [(13)C-(2)H(2)]citrulline, [(2)H(5)]phenylalanine, and [(2)H(2)]tyrosine. Plasma pyruvate and lactate concentrations were determined by fully automated HPLC. Pre-endotoxin arginine appearance was significantly lower in the RE group than in the CE group (P = 0.002). During endotoxemia, arginine appearance increased in the CE animals but not in the RE animals (P = 0.04). In addition, nitric oxide production was significantly lower in the RE animals (P endotoxemia in the RE group than in the CE group (P endotoxemia but increased significantly during endotoxemia in the RE group (P = 0.04). A well-nourished condition before prolonged endotoxemia results in a better ability to adapt to endotoxin-induced metabolic deterioration of arginine-nitric oxide metabolism than does reduced caloric intake before endotoxemia.

  14. The crucial role of l-arginine in macrophage activation: What you need to know about it.

    Science.gov (United States)

    Pekarova, Michaela; Lojek, Antonin

    2015-09-15

    Nowadays, it is well recognized that amino acids are powerful molecules responsible for regulatory control over fundamental cellular processes. However, our understanding of the signaling cascades involved in amino acid sensing in organisms, as well as signal initiation, is largely limited. This is also the case of semi-essential amino acid l-arginine, which has multiple metabolic fates, and it is considered as one of the most versatile amino acids. Recently, some new and important facts have been published considering the role of l-arginine in the regulation of inflammatory processes in several human and mouse models, mediated also via the regulation of macrophage activation. Therefore, this mini review focuses on the actual summarization of information about (i) l-arginine bioavailability in organism, (ii) l-arginine-dependent regulation of nitric oxide synthase expression and nitric oxide production, and importantly (iii) its role in the activation of intracellular signaling pathways and G-protein-coupled receptors in macrophages. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effects of L-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia

    NARCIS (Netherlands)

    Poeze, Martijn; Bruins, Maaike J.; Kessels, Fons; Luiking, Yvette C.; Lamers, Wouter H.; Deutz, Nicolaas Ep

    2011-01-01

    Background: Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. Objective: The objective was to evaluate the effects of L-arginine pretreatment on arginine-nitric oxide (NO) production and hepatosplanchnic perfusion during

  16. Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

    KAUST Repository

    Shah, Dhawal

    2011-09-21

    We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, Γ XP, contrary to conventional thinking that positive Γ XP\\'s indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine\\'s preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine\\'s interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on Γ XP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. © 2011 American Institute of Chemical Engineers (AIChE).

  17. A comparison of DNA compaction by arginine and lysine peptides: a physical basis for arginine rich protamines.

    Science.gov (United States)

    DeRouchey, Jason; Hoover, Brandon; Rau, Donald C

    2013-04-30

    Protamines are small, highly positively charged peptides used to package DNA at very high densities in sperm nuclei. Tight DNA packing is considered essential for the minimization of DNA damage by mutagens and reactive oxidizing species. A striking and general feature of protamines is the almost exclusive use of arginine over lysine for the positive charge to neutralize DNA. We have investigated whether this preference for arginine might arise from a difference in DNA condensation by arginine and lysine peptides. The forces underlying DNA compaction by arginine, lysine, and ornithine peptides are measured using the osmotic stress technique coupled with X-ray scattering. The equilibrium spacings between DNA helices condensed by lysine and ornithine peptides are significantly larger than the interhelical distances with comparable arginine peptides. The DNA surface-to-surface separation, for example, is some 50% larger with polylysine than with polyarginine. DNA packing by lysine rich peptides in sperm nuclei would allow much greater accessibility to small molecules that could damage DNA. The larger spacing with lysine peptides is caused by both a weaker attraction and a stronger short-range repulsion relative to that of the arginine peptides. A previously proposed model for binding of polyarginine and protamine to DNA provides a convenient framework for understanding the differences between the ability of lysine and arginine peptides to assemble DNA.

  18. PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome

    OpenAIRE

    Girardot, Michael; Hirasawa, Ryutaro; Kacem, Salim; Fritsch, Lauriane; Pontis, Julien; Kota, Satya K.; Filipponi, Doria; Fabbrizio, Eric; Sardet, Claude; Lohmann, Felix; Kadam, Shilpa; Ait-Si-Ali, Slimane; Feil, Robert

    2013-01-01

    Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been reported to occur at several repressed genes, but its specific regulation and genomic distribution remained unclear. Here, we show that the type-II protein arginine methyltransferase PRMT5 controls H4R3me2s in mouse embryonic fibroblasts (MEFs). In these differentiated cells, we find that the genome-wide pattern of H4R3me2s is highly similar to that in embryonic stem cells. In both the cell types, H4R3me2s peaks are det...

  19. L-Arginine Pathway in COPD Patients with Acute Exacerbation

    DEFF Research Database (Denmark)

    Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor

    2016-01-01

    (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD. METHODS: L-arginine metabolites quantified by high......-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects. RESULTS: Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p ....001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p

  20. THE INFLUENCE OF Nω-NITRO-L-ARGININE METHYL ESTER ON ARGININE AND POLYAMINE METABOLISM IN RAT’S BRAIN TISSUE DURING EXPOSITION TO MICROWAVE RADIATION

    Directory of Open Access Journals (Sweden)

    Maja Jocic

    2009-01-01

    Full Text Available Exposition to microwave radiation (MW from mobile phones, satellite communi-cations, radio relays, radars and microwave devices in medicine induce disturbances in different organ systems. It has been shown that MW from mobile phones induce increasing of oxidative stress and apoptosis of neurons with impairment of blood brain barrier, disturbances of memory and space orientation. Citrulline and nitric oxide -NO are products of L-arginine by NO sintase-NOS. L-ornithine and polyamines are products of L-arginine by arginase. Nω-nitro-L-arginine methyl ester (L-NAME competitive inhibits NOS and exerts neuroprotective effects.The aim of this investigation was to determine the arginase, PAO and DAO activity, concentration of citrulline, as well as the effects of L-NAME on arginine and polyamine metabolism in brain tissue of rats exposed to MW.Four groups of Wistar rats were investigated during 60 days: I-control-sham exposed, II (L-NAME-rats treated with L-NAME (5 mg/kg b.w. i.p., III (MW-rats exposed to MW (4 h/day, IV (MW + L-NAME. The source of MW was mobile test telephone.Decreasing activity of arginase (0.19±0.04 vs. 0.25±0.05 mmol/mg prot; p<0.01 and increasing of citrulline concentration (10.34±0.49 vs. 7.83 ±0.41 mmol/mg prot; p<0.001 were registered in the brain of MW exposed rats compared to controls. In L-NAME group there was a decrease of citrulline level (p<0.05, and increase in arginase activity (p<0.05 compared to controls. In the brain of exposed rats, the activity of PAO was significantly increased, while the activity of DAO was significantly increased vs. controls (1.12±0.10 vs. 0.79±0.09 U/mg prot; p<0.001 and 0.51±0.06 vs. 0.65±0.06 U/mg prot; p<0.05, prospectively. In MW+L-NAME group we registered increasing of DAO activity (0.61±0.04 vs. 0.51±0.06 U/mg prot; p<0.05 in the brain tissue compared with MW group.Having in the mind the obtained results we concluded that L-NAME ex

  1. Hyperbranched lysine-arginine copolymer for gene delivery.

    Science.gov (United States)

    Peng, Qi; Zhu, Jianjun; Yu, Yongsheng; Hoffman, Lee; Yang, Xingkun

    2015-01-01

    Based on the reactivity of amine groups and carboxyl groups of L-lysine and L-arginine, thermal polymerization of these two natural amino acids results in hyperbranched lysine-arginine copolymers (P-lys-argX, where X refers to the relevant molar ratio of arginine to lysine). Hyperbranched polylysine (P-lys) and two derivatives (P-lys-arg0.10 and P-lys-arg0.20) have been prepared. The arginine-rich hyperbranched polymers can interact with plasmid DNA to form nano-sized particles. The polyplexes were physicochemically analyzed by agarose gel electrophoresis, dynamic light scattering, and zeta potential measurements. Furthermore, their transfection efficiency was assessed, employing COS-7, 293T, and HeLa cell lines. It was found that P-lys showed poorly in its ability of condensation with DNA and transfection efficiency. On the other hand, arginine-rich products resulted to significant enhancement of its transfection efficiency, which is dependent on the content of arginine in the polymers, and the cell line used. P-lys-arg0.20 exhibited better transfection efficiency under all the condition studied. Besides, P-lys-arg0.20 showed lower toxicity in COS-7 cells.

  2. Reference Intervals for Plasma l-Arginine and the l-Arginine:Asymmetric Dimethylarginine Ratio in the Framingham Offspring Cohort123

    OpenAIRE

    Lüneburg, Nicole; Xanthakis, Vanessa; Schwedhelm, Edzard; Sullivan, Lisa M.; Maas, Renke; Anderssohn, Maike; Riederer, Ulrich; Glazer, Nicole L.; Vasan, Ramachandran S.; Böger, Rainer H.

    2011-01-01

    l-Arginine, as a precursor of NO synthesis, has attracted much scientific attention in recent years. Experimental mouse models suggest that l-arginine supplementation can retard, halt, or even reverse atherogenesis. In human studies, supplementation with l-arginine improved endothelium-dependent vasodilation. However, l-arginine levels are best interpreted in the context of levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of NO synthase. Thus, reference limits for circula...

  3. Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model.

    Science.gov (United States)

    Edwards, Adam B; Anderton, Ryan S; Knuckey, Neville W; Meloni, Bruno P

    2017-02-01

    In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with D-amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1-6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.

  4. Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation

    Science.gov (United States)

    Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong

    2016-01-01

    Purpose Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Materials and Methods Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. Results SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. NG-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. Conclusion These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions. PMID:27593859

  5. Prediction of twin-arginine signal peptides

    Directory of Open Access Journals (Sweden)

    Widdick David

    2005-07-01

    Full Text Available Abstract Background Proteins carrying twin-arginine (Tat signal peptides are exported into the periplasmic compartment or extracellular environment independently of the classical Sec-dependent translocation pathway. To complement other methods for classical signal peptide prediction we here present a publicly available method, TatP, for prediction of bacterial Tat signal peptides. Results We have retrieved sequence data for Tat substrates in order to train a computational method for discrimination of Sec and Tat signal peptides. The TatP method is able to positively classify 91% of 35 known Tat signal peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than a complementary rule based prediction method. Conclusion The method developed here is able to discriminate Tat signal peptides from cytoplasmic proteins carrying a similar motif, as well as from Sec signal peptides, with high accuracy. The method allows filtering of input sequences based on Perl syntax regular expressions, whereas hydrophobicity discrimination of Tat- and Sec-signal peptides is carried out by an artificial neural network. A potential cleavage site of the predicted Tat signal peptide is also reported. The TatP prediction server is available as a public web server at http://www.cbs.dtu.dk/services/TatP/.

  6. Fluorometric enzymatic assay of L-arginine

    Science.gov (United States)

    Stasyuk, Nataliya; Gayda, Galina; Yepremyan, Hasmik; Stepien, Agnieszka; Gonchar, Mykhailo

    2017-01-01

    The enzymes of L-arginine (further - Arg) metabolism are promising tools for elaboration of selective methods for quantitative Arg analysis. In our study we propose an enzymatic method for Arg assay based on fluorometric monitoring of ammonia, a final product of Arg splitting by human liver arginase I (further - arginase), isolated from the recombinant yeast strain, and commercial urease. The selective analysis of ammonia (at 415 nm under excitation at 360 nm) is based on reaction with o-phthalaldehyde (OPA) in the presence of sulfite in alkali medium: these conditions permit to avoid the reaction of OPA with any amino acid. A linearity range of the fluorometric arginase-urease-OPA method is from 100 nM to 6 μМ with a limit of detection of 34 nM Arg. The method was used for the quantitative determination of Arg in the pooled sample of blood serum. The obtained results proved to be in a good correlation with the reference enzymatic method and literature data. The proposed arginase-urease-OPA method being sensitive, economical, selective and suitable for both routine and micro-volume formats, can be used in clinical diagnostics for the simultaneous determination of Arg as well as urea and ammonia in serum samples.

  7. Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

    Science.gov (United States)

    Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

    2016-02-01

    Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

  8. Arginine dependence of tumor cells: targeting a chink in cancer's armor.

    Science.gov (United States)

    Patil, M D; Bhaumik, J; Babykutty, S; Banerjee, U C; Fukumura, D

    2016-09-22

    Arginine, one among the 20 most common natural amino acids, has a pivotal role in cellular physiology as it is being involved in numerous cellular metabolic and signaling pathways. Dependence on arginine is diverse for both tumor and normal cells. Because of decreased expression of argininosuccinate synthetase and/or ornithine transcarbamoylase, several types of tumor are auxotrophic for arginine. Deprivation of arginine exploits a significant vulnerability of these tumor cells and leads to their rapid demise. Hence, enzyme-mediated arginine depletion is a potential strategy for the selective destruction of tumor cells. Arginase, arginine deiminase and arginine decarboxylase are potential enzymes that may be used for arginine deprivation therapy. These arginine catabolizing enzymes not only reduce tumor growth but also make them susceptible to concomitantly administered anti-cancer therapeutics. Most of these enzymes are currently under clinical investigations and if successful will potentially be advanced as anti-cancer modalities.

  9. L-Arginine Supplementation and Metabolism in Asthma

    Directory of Open Access Journals (Sweden)

    Angela Linderholm

    2011-01-01

    Full Text Available L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05, ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05 and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05 on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

  10. Determination of l-arginine and NG, NG - and NG, NG' -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives.

    Science.gov (United States)

    Heresztyn, Tamila; Worthley, Matthew I; Horowitz, John D

    2004-06-15

    A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' -dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N-hydroxysuccinimidyl carbamate) is described. The fluorescent derivatives produced are extremely stable enabling routine processing of large numbers of samples. Arginine and its metabolites are extracted from plasma on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard, derivatised and separated on a C18 column with acetonitrile in 0.1M sodium acetate buffer pH 6. Separation of the stereoisomers ADMA and SDMA was excellent and improvements to the solid phase extraction (SPE) procedure enabled good recovery (>80%) of arginine, ADMA and SDMA. The utility of the method is exemplified by comparison of plasma concentrations of ADMA, SDMA and arginine in healthy volunteers and diabetic/ischaemic patients.

  11. Arginine kinase in Phytomonas, a trypanosomatid parasite of plants.

    Science.gov (United States)

    Canepa, Gaspar E; Carrillo, Carolina; Miranda, Mariana R; Sayé, Melisa; Pereira, Claudio A

    2011-09-01

    Phytomonas are trypanosomatid plant parasites closely related to parasites that cause several human diseases. Little is known about the biology of these organisms including aspects of their metabolism. Arginine kinase (E.C. 2.7.3.3) is a phosphotransferase which catalyzes the interconversion between the phosphagen phosphoarginine and ATP. This enzyme is present in some invertebrates and is a homolog of another widely distributed phosphosphagen kinase, creatine kinase. In this work, a single canonical arginine kinase isoform was detected in Phytomonas Jma by enzymatic activity assays, PCR, and Western Blot. This arginine kinase is very similar to the canonical isoforms found in T. cruzi and T. brucei, presenting about 70% of amino acid sequence identity and a very similar molecular weight (40kDa). The Phytomonas phosphagen system seems to be very similar to T. cruzi, which has only one isoform, or T. brucei (three isoforms); establishing a difference with other trypanosomatids, such as Leishmania, which completely lacks phosphagen kinases, probably by the presence of the arginine-consuming enzyme, arginase. Finally, phylogenetic analysis suggests that Kinetoplastids' arginine kinase was acquired, during evolution, from the arthropod vectors by horizontal gene transfer. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. L-arginine as dietary supplement for improving microvascular function.

    Science.gov (United States)

    Melik, Ziva; Zaletel, Polona; Virtic, Tina; Cankar, Ksenija

    2017-01-01

    Reduced availability of nitric oxide leads to dysfunction of endothelium which plays an important role in the development of cardiovascular diseases. The aim of the present study was to determine whether the dietary supplement L-arginine improves the endothelial function of microvessels by increasing nitric oxide production. We undertook experiments on 51 healthy male volunteers, divided into 4 groups based on their age and physical activity since regular physical activity itself increases endothelium-dependent vasodilation. The skin laser Doppler flux was measured in the microvessels before and after the ingestion of L-arginine (0.9 g). The endothelium-dependent vasodilation was assessed by acetylcholine iontophoresis and the endothelium-independent vasodilation by sodium nitroprusside iontophoresis. In addition, we measured endothelium-dependent and endothelium-independent vasodilation in 81 healthy subjects divided into four age groups. After the ingestion of L-arginine, the endothelium-dependent vasodilation in the young trained subjects increased (paired t-test, p L-arginine. With aging endothelium-independent vasodilation decreased while endothelium-dependent vasodilation remained mainly unchanged. Obtained results demonstrated that a single dose of L-arginine influences endothelium-dependent vasodilation predominantly in young, trained individuals.

  13. Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?

    Science.gov (United States)

    Sureda, Antoni; Pons, Antoni

    2012-01-01

    Dietary L-citrulline malate supplements may increase levels of nitric oxide (NO) metabolites, although this response has not been related to an improvement in athletic performance. NO plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. L-Arginine is the main precursor of NO via nitric oxide synthase (NOS) activity. Additionally, L-citrulline has been indicated to be a second NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. The importance of L-citrulline as an ergogenic support derives from the fact that L-citrulline is not subject to pre-systemic elimination and, consequently, could be a more efficient way to elevate extracellular levels of L-arginine by itself. L-Citrulline malate can develop beneficial effects on the elimination of NH(3) in the course of recovery from exhaustive muscular exercise and also as an effective precursor of L-arginine and creatine. Dietary supplementation with L-citrulline alone does not improve exercise performance. The ergogenic response of L-citrulline or L-arginine supplements depends on the training status of the subjects. Studies involving untrained or moderately healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly-trained subjects were supplemented, no positive effect on performance was indicated. Copyright © 2012 S. Karger AG, Basel.

  14. Guanidinium Group Remains Protonated in a Strongly Basic Arginine Solution.

    Science.gov (United States)

    Xu, Bo; Jacobs, Michael I; Kostko, Oleg; Ahmed, Musahid

    2017-06-20

    Knowledge of the acid dissociation constant of an amino acid has very important ramifications in the biochemistry of proteins and lipid bilayers in aqueous environments because charge and proton transfer depend on its value. The acid dissociation constant for the guanidinium group in arginine has historically been posited as 12.5, but there is substantial variation in published values over the years. Recent experiments suggest that the dissociation constant for arginine is much higher than 12.5, which explains why the arginine guanidinium group retains its positive charge under all physiological conditions. In this work, we use X-ray photoelectron spectroscopy to study unsupported, aqueous arginine nanoparticles. By varying the pH of the constituent solution, we provide evidence that the guanidinium group is protonated even in a very basic solution. By analyzing the energy shifts in the C and N X-ray photoelectron spectra, we establish a molecular level picture of how charge and proton transport in aqueous solutions of arginine occur. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Safety of long-term dietary supplementation with L-arginine in rats.

    Science.gov (United States)

    Yang, Ying; Wu, Zhenlong; Jia, Sichao; Dahanayaka, Sudath; Feng, Shuo; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

    2015-09-01

    This study was conducted with rats to determine the safety of long-term dietary supplementation with L-arginine. Beginning at 6 weeks of age, male and female rats were fed a casein-based semi-purified diet containing 0.61 % L-arginine and received drinking water containing L-arginine-HCl (0, 1.8, or 3.6 g L-arginine/kg body-weight/day; n = 10/group). These supplemental doses of L-arginine were equivalent to 0, 286, and 573 mg L-arginine/kg body-weight/day, respectively, in humans. After a 13-week supplementation period, blood samples were obtained from rats for biochemical analyses. Supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, homoarginine, urea, and nitric oxide metabolites without affecting those for lysine, histidine, or methylarginines, while reducing plasma concentrations of ammonia, glutamine, free fatty acids, and triglycerides. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Based on general appearance, feeding behavior, and physiological parameters, all animals showed good health during the entire experimental period; Plasma concentrations of all measured hormones (except leptin) did not differ between control and arginine-supplemented rats. L-Arginine supplementation reduced plasma levels of leptin. Additionally, L-arginine supplementation increased L-arginine:glycine amidinotransferase activity in kidneys but not in the liver or small intestine, suggesting tissue-specific regulation of enzyme expression by L-arginine. Collectively, these results indicate that dietary supplementation with L-arginine (e.g., 3.6 g/kg body-weight/day) is safe in rats for at least 91 days. This dose is equivalent to 40 g L-arginine/kg body-weight/day for a 70-kg person. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.

  16. Effect of dietary taurine and arginine supplementation on bone mineral density in growing female rats.

    Science.gov (United States)

    Choi, Mi-Ja; Chang, Kyung Ja

    2013-01-01

    The purpose of this study was to determine the effect of arginine or -taurine alone and taurine plus arginine on bone mineral density (BMD) and markers of bone formation and bone resorption in growing female rats. Forty female SD rats (75 ± 5 g) were randomly divided into four groups (control, taurine, arginine, taurine + arginine group) and treatment lasted for 9 weeks. All rats were fed on a diet and deionized water. BMD and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur. The serum and urine concentrations of calcium and phosphorus were determined. Bone formation was measured by serum osteocalcin and alkaline phosphatase concentrations, and the bone resorption rate was measured by deoxypyridinoline cross-links. Femur BMD was significantly increased in the group with taurine supplementation and femur BMC/weight was significantly increased in the group with arginine + taurine supplementation. Rats fed an arginine or taurine supplemental diet increased femur BMD or femur BMC, but a taurine + arginine-supplemented diet does not have a better effect than arginine or taurine alone in the spine BMD. The femur BMC, expressed per body weight, was higher in arginine + taurine group than in the taurine or arginine group. The results of this study suggest that taurine + arginine supplementation may be beneficial on femur BMC in growing female rats. Additional work is needed to clarify the interactive effects between the taurine and arginine to determine whether dietary intakes of arginine and taurine affect bone quality in growing rats.

  17. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity.

    Science.gov (United States)

    Wijnands, Karolina A P; Meesters, Dennis M; van Barneveld, Kevin W Y; Visschers, Ruben G J; Briedé, Jacob J; Vandendriessche, Benjamin; van Eijk, Hans M H; Bessems, Babs A F M; van den Hoven, Nadine; von Wintersdorff, Christian J H; Brouckaert, Peter; Bouvy, Nicole D; Lamers, Wouter H; Cauwels, Anje; Poeze, Martijn

    2015-06-29

    Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with L-arginine supplementation exhibited less consistent results; however, L-citrulline, the precursor of L-arginine, may be a promising alternative. In this study, we determined the effects of L-citrulline compared to L-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with L-citrulline or L-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. L-arginine and L-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that L-citrulline, and not L-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

  18. Effects of L-Arginine Supplementation on Blood Pressure Reduction Pre-, Peri-, and Post-Cardiovascular Stimulus in Hypertensive Subjects with Different Angiotensin-Converting-Enzyme Genotypes

    Directory of Open Access Journals (Sweden)

    Malfatti Carlos Ricardo Maneck

    2014-08-01

    Full Text Available Purpose. The present study investigated whether L-arginine supplementation reduces blood pressure (BP in hypertensive subjects with different ACE genotypes. Methods. Eight male hypertensive patients received L-arginine (2 or 4 g/day or a placebo for a period of 4 days prior an exercise test. Statistical analysis consisted of one-way analysis of variance. Results. L-arginine supplementation induced a statistically significant (p ⋋ 0.05 reduction in systolic BP measured during rest (reductions of 7.8% and 12.3% with 2 and 4 g/day, respectively, exercise (reductions of 11.8% and 10.4% with 2 and 4 g/day, respectively, and recovery (reductions of 11.7% and 10.7% with 2 and 4 g/day, respectively. The observed magnitude of BP reduction suggests an association with ACE polymorphism; a larger effect was seen with the II and DI genotypes compared with the DD genotype (II: 121 mmHg and DI: 133 mmHg vs. DD: 144 mmHg. Conclusions. The results showed that L-arginine supplementation at low doses was efficient in reducing BP and that vasodilator actions that occurred through the secretion of nitric oxide might be ACE genotype dependent.

  19. Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine with Morbidity and Mortality in Patients with Necrotizing Soft Tissue Infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Rasmussen, Lars Simon; Garred, Peter

    2017-01-01

    evaluated the association between nitrite, asymmetric dimethylarginine (ADMA), L-arginine, L-arginine/ADMA-ratio and outcome. METHODS: We analyzed plasma from 141 NSTI patients taken upon hospital admission. The severity of NSTI was assessed by the presence of septic shock, SAPS II, SOFA score, use of renal.......47-0.90) vs. (0.52 μmol/L (0.34-0.70), p = 0.028), and ADMA levels correlated positively with SAPS II (rho = 0.32, p = 0.0002) and SOFA scores (rho = 0.22, p = 0.01). In a logistic regression analysis, an L-arginine/ADMA-ratio below 101.59 was independently associated with 28-day mortality, OR 6.03 (95% CI, 1...... and patients with a low baseline L-arginine/ADMA-ratio were at higher risk of dying within 28 days after hospital admission.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download...

  20. L-arginine is an effective medication for prevention of endothelial dysfunction, a predictor of anthracycline cardiotoxicity in patients with acute leukemia.

    Science.gov (United States)

    Skrypnyk, I; Maslova, G; Lymanets, T; Gusachenko, I

    2017-12-01

    To evaluate the effectiveness of L-arginine in the prevention of endothelial dysfunction, which may be a predictor of anthracycline-induced myocardial injury, in patients with acute leukemia (AL) on the background of anthracycline antibiotics low cumulative doses from 100 to 200 mg/m 2 . A total of 81 adult AL patients (38 males and 43 females with the age of 16-59 years) were studied. The patients were divided into two groups: group I (n = 34), AL patients treated with chemotherapy (CT) and L-arginine hydrochloride; group II (n = 47) - AL patients treated with CT only. Cardiac evaluation and endothelial function assessment were performed at baseline and after second CT. Electrocardiography (ECG) parameters, lipid peroxidation activity, antioxidant protection and NO system state were evaluated. The bioelectric activity abnormalities of the myocardium were observed in studied patients with low cardiac risk after induction CT. In case of L-arginine administration, only minimal daily ECG changes were recorded. A significant difference in the lipid peroxidation and antioxidant defense system activity in patients of groups I and II was determined. We noticed deepening of endothelial dysfunction on the background of cytostatic therapy with anthracycline antibiotics compared with baseline values in patients of group II. It was found that prophylactic L-arginine increases superoxide dismutase level and reduces the total NOS activity due to its inducible isoform. The leading factor of anthracycline-induced cardiotoxicity is the imbalance between free radical generation and their inactivation that leads to endothelial dysfunction development. L-arginine eliminates the prooxidant-antioxidant imbalance and improves the endothelial function.

  1. Mammalian protein arginine methyltransferase 7 (PRMT7) specifically targets RXR sites in lysine- and arginine-rich regions.

    Science.gov (United States)

    Feng, You; Maity, Ranjan; Whitelegge, Julian P; Hadjikyriacou, Andrea; Li, Ziwei; Zurita-Lopez, Cecilia; Al-Hadid, Qais; Clark, Amander T; Bedford, Mark T; Masson, Jean-Yves; Clarke, Steven G

    2013-12-27

    The mammalian protein arginine methyltransferase 7 (PRMT7) has been implicated in roles of transcriptional regulation, DNA damage repair, RNA splicing, cell differentiation, and metastasis. However, the type of reaction that it catalyzes and its substrate specificity remain controversial. In this study, we purified a recombinant mouse PRMT7 expressed in insect cells that demonstrates a robust methyltransferase activity. Using a variety of substrates, we demonstrate that the enzyme only catalyzes the formation of ω-monomethylarginine residues, and we confirm its activity as the prototype type III protein arginine methyltransferase. This enzyme is active on all recombinant human core histones, but histone H2B is a highly preferred substrate. Analysis of the specific methylation sites within intact histone H2B and within H2B and H4 peptides revealed novel post-translational modification sites and a unique specificity of PRMT7 for methylating arginine residues in lysine- and arginine-rich regions. We demonstrate that a prominent substrate recognition motif consists of a pair of arginine residues separated by one residue (RXR motif). These findings will significantly accelerate substrate profile analysis, biological function study, and inhibitor discovery for PRMT7.

  2. Mammalian Protein Arginine Methyltransferase 7 (PRMT7) Specifically Targets RXR Sites in Lysine- and Arginine-rich Regions*

    Science.gov (United States)

    Feng, You; Maity, Ranjan; Whitelegge, Julian P.; Hadjikyriacou, Andrea; Li, Ziwei; Zurita-Lopez, Cecilia; Al-Hadid, Qais; Clark, Amander T.; Bedford, Mark T.; Masson, Jean-Yves; Clarke, Steven G.

    2013-01-01

    The mammalian protein arginine methyltransferase 7 (PRMT7) has been implicated in roles of transcriptional regulation, DNA damage repair, RNA splicing, cell differentiation, and metastasis. However, the type of reaction that it catalyzes and its substrate specificity remain controversial. In this study, we purified a recombinant mouse PRMT7 expressed in insect cells that demonstrates a robust methyltransferase activity. Using a variety of substrates, we demonstrate that the enzyme only catalyzes the formation of ω-monomethylarginine residues, and we confirm its activity as the prototype type III protein arginine methyltransferase. This enzyme is active on all recombinant human core histones, but histone H2B is a highly preferred substrate. Analysis of the specific methylation sites within intact histone H2B and within H2B and H4 peptides revealed novel post-translational modification sites and a unique specificity of PRMT7 for methylating arginine residues in lysine- and arginine-rich regions. We demonstrate that a prominent substrate recognition motif consists of a pair of arginine residues separated by one residue (RXR motif). These findings will significantly accelerate substrate profile analysis, biological function study, and inhibitor discovery for PRMT7. PMID:24247247

  3. Contents of corticotropin-releasing hormone and arginine vasopressin immunoreativity in the spleen and thymus during a chronic inflammatory stress

    DEFF Research Database (Denmark)

    Chowdrey, H.S.; Lightman, S.L.; Harbuz, M.S.

    1994-01-01

    Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin......Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin...

  4. Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta.

    Science.gov (United States)

    Cooke, J P; Andon, N A; Girerd, X J; Hirsch, A T; Creager, M A

    1991-03-01

    Reduced synthesis of endothelium-derived relaxing factor (EDRF) may explain impaired endothelium-dependent vasodilation in hypercholesterolemia. Accordingly, we designed studies to determine if endothelium-dependent relaxation in hypercholesterolemic rabbits may be restored by supplying L-arginine, the precursor of EDRF. Normal or hypercholesterolemic rabbits received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes. Subsequently, animals were killed, thoracic aortas were harvested, and vascular rings were studied in vitro. Rings were contracted by norepinephrine and relaxed by acetylcholine chloride or sodium nitroprusside. Vasorelaxation was quantified by determining the maximal response (expressed as percent relaxation of the contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as -log M). In vessels from hypercholesterolemic animals receiving vehicle, there was a fivefold rightward shift in sensitivity to acetylcholine compared with normal animals (p = 0.05, n = 5 in each group). In vessels from hypercholesterolemic animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16% versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05 versus vehicle). Arginine did not affect maximal and EC50 responses to acetylcholine in vessels from normal animals. Arginine did not potentiate endothelium-independent responses in either group. We conclude that the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.

  5. Plasma glucagon responses to L-arginine in various diseases

    International Nuclear Information System (INIS)

    Morita, Nobuto; Hayakawa, Hiroyuki; Kawai, Kohzo; Noto, Yutaka; Ohno, Taro

    1978-01-01

    To clarify the mechanism of abnormal glucose metabolism in the secondary diabetes, we examined the dynamics of plasma glucagon levels in various diseases which may accompany glucose intolerance. Plasma glucagon responses to L-arginine were observed in 20 liver cirrhotics, 8 patients with chronic renal failure, 6 patients with chronic pancreatitis, 4 patients, with hyperthyroidism, 22 diabetics and 9 normal controls. Plasma glucagon levels were determined by the radioimmunoassay method of Unger using 125 I-glucagon and antiserum 30K which is specific for pancreatic glucagon. In the cirrhotics, the plasma glucagon responses to L-arginine were significantly higher than in normal controls. The patients whose BSP retention at 45 minutes were above 30% showed higher plasma glucagon responses than in the patients whose BSP retention at 45 minutes were below 30%, suggesting that the more severely the liver was damaged, the more the plasma glucagon levels were elevated. In the patients with chronic renal failure, the plasma glucagon responses to L-arginine were also significantly higher than in normal controls. These abnormal levels were not improved by a hemodialysis, although serum creatinine levels were fairly decreased. In the patients with chronic pancreatitis, the plasma glucagon responses to L-arginine were the same as those in normal controls. In the patients with hyperthyroidism the plasma glucagon responses to L-arginine seemed to be lower than normal controls. In the diabetics, the plasma glucagon responses to L-arginine were almost the same as in normal controls. However their glucagon levels seemed to be relatively high, considering the fact that diabetics had high blood glucose levels. (auth.)

  6. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  7. Mimicking of Arginine by Functionalized N(ω)-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples.

    Science.gov (United States)

    Keller, Max; Kuhn, Kilian K; Einsiedel, Jürgen; Hübner, Harald; Biselli, Sabrina; Mollereau, Catherine; Wifling, David; Svobodová, Jaroslava; Bernhardt, Günther; Cabrele, Chiara; Vanderheyden, Patrick M L; Gmeiner, Peter; Buschauer, Armin

    2016-03-10

    Derivatization of biologically active peptides by conjugation with fluorophores or radionuclide-bearing moieties is an effective and commonly used approach to prepare molecular tools and diagnostic agents. Whereas lysine, cysteine, and N-terminal amino acids have been mostly used for peptide conjugation, we describe a new, widely applicable approach to peptide conjugation based on the nonclassical bioisosteric replacement of the guanidine group in arginine by a functionalized carbamoylguanidine moiety. Four arginine-containing peptide receptor ligands (angiotensin II, neurotensin(8-13), an analogue of the C-terminal pentapeptide of neuropeptide Y, and a neuropeptide FF analogue) were subject of this proof-of-concept study. The N(ω)-carbamoylated arginines, bearing spacers with a terminal amino group, were incorporated into the peptides by standard Fmoc solid phase peptide synthesis. The synthesized chemically stable peptide derivatives showed high receptor affinities with Ki values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described.

  8. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

    Science.gov (United States)

    Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2017-06-25

    Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture.

    Science.gov (United States)

    Griffith, R S; DeLong, D C; Nelson, J D

    1981-01-01

    In the studies conducted, arginine deficiency suppressed herpes simplex virus replication in tissue culture. Lysine, an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. The in vitro data may be the basis for the observation that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.

  10. Expression of protein arginine methyltransferase-5 in oral squamous cell carcinoma and its significance in epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Amano, Yusuke; Matsubara, Daisuke; Yoshimoto, Taichiro; Tamura, Tomoko; Nishino, Hiroshi; Mori, Yoshiyuki; Niki, Toshiro

    2018-03-30

    Protein arginine methyltransferases (PRMT) 5, a member of type II arginine methyltransferases, catalyzes the symmetrical dimethylation of arginine residues on histone and non-histone substrates. Although the overexpression of PRMT5 has been reported in various cancers, its role in oral squamous cell carcinoma (OSCC) has not been elucidated. In the present study, we immunohistochemically examined the expression of PRMT5 in surgically resected oral epithelial dysplasia (OED, n = 8), oral intraepithelial neoplasia (OIN)/carcinoma in situ (CIS) (n = 11) and OSCC (n = 52) with or without contiguous OED lesions. In the normal epithelium, PRMT5 was weakly expressed in the cytoplasm of basal layer cells. In OED, OIN/CIS, and OSCC, its expression consistently and uniformly increased in the cytoplasm of dysplastic and cancer cells. Moreover, nuclear and cytoplasmic localization was detected in the invasive front of cancer cells, particularly in cases showing poor differentiation or aggressive invasion patterns. The concomitant nuclear and cytoplasmic expression of PRMT5 correlated with the loss of E-cadherin and cytokeratin 17, and the upregulation of vimentin, features that are both indicative of epithelial-to-mesenchymal transition. PRMT5 may play a role from early oncogenesis through to the progression of OSCC, particularly in the aggressive mode of stromal invasion. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  11. Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study

    NARCIS (Netherlands)

    Buijs, Nikki; Brinkmann, Saskia J. H.; Oosterink, J. Efraim; Luttikhold, Joanna; Schierbeek, Henk; Wisselink, Willem; Beishuizen, Albertus; van Goudoever, Johannes B.; Houdijk, Alexander P. J.; van Leeuwen, Paul A. M.; Vermeulen, Mechteld A. R.

    2014-01-01

    Arginine plays a role in many different pathways in multiple cell types. Consequently, a shortage of arginine, caused by pathologic conditions such as cancer or injury, has the potential to disturb many cellular and organ functions. Glutamine is the ultimate source for de novo synthesis of arginine

  12. L-arginine increases nitric oxide and attenuates pressor and heart ...

    African Journals Online (AJOL)

    L-Arginine supplementation increased plasma L-Arginine concentration ([R]) in both groups of subjects (p<0.001 in each group) and serum nitric oxide metabolites concentration ([NOx]) (p<0.01 in each group). Change (Δ) [R] correlated positively with Δ [NOx] in both groups (+ 0.7 in each group). L-Arginine supplementation ...

  13. An Association between l-Arginine/Asymmetric Dimethyl Arginine Balance, Obesity, and the Age of Asthma Onset Phenotype

    Science.gov (United States)

    Comhair, Suzy A. A.; Hazen, Stanley L.; Powers, Robert W.; Khatri, Sumita S.; Bleecker, Eugene R.; Busse, William W.; Calhoun, William J.; Castro, Mario; Fitzpatrick, Anne M.; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar N.; Moore, Wendy C.; Peters, Stephen P.; Teague, W. Gerald; Chung, Kian Fan; Erzurum, Serpil C.; Wenzel, Sally E.

    2013-01-01

    Rationale: Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (FeNO). This may be explained by an increase in the concentration of asymmetric dimethyl arginine (ADMA) relative to l-arginine, which can lead to greater nitric oxide synthase uncoupling. Objectives: To compare this mechanism across age of asthma onset groups and determine its association with asthma morbidity and lung function. Methods: Cross-sectional study of participants from the Severe Asthma Research Program, across early- (12 yr) onset asthma phenotypes. Measurements and Main Results: Subjects with late-onset asthma had a higher median plasma ADMA level (0.48 μM, [interquartile range (IQR), 0.35–0.7] compared with early onset, 0.37 μM [IQR, 0.29–0.59], P = 0.01) and lower median plasma l-arginine (late onset, 52.3 [IQR, 43–61] compared with early onset, 51 μM [IQR 39–66]; P = 0.02). The log of plasma l-arginine/ADMA was inversely correlated with BMI in the late- (r = −0.4, P = 0.0006) in contrast to the early-onset phenotype (r = −0.2, P = 0.07). Although FeNO was inversely associated with BMI in the late-onset phenotype (P = 0.02), the relationship was lost after adjusting for l-arginine/ADMA. Also in this phenotype, a reduced l-arginine/ADMA was associated with less IgE, increased respiratory symptoms, lower lung volumes, and worse asthma quality of life. Conclusions: In late-onset asthma phenotype, plasma ratios of l-arginine to ADMA may explain the inverse relationship of BMI to FeNO. In addition, these lower l-arginine/ADMA ratios are associated with reduced lung function and increased respiratory symptom frequency, suggesting a role in the pathobiology of the late-onset phenotype. PMID:23204252

  14. Reference Intervals for Plasma l-Arginine and the l-Arginine:Asymmetric Dimethylarginine Ratio in the Framingham Offspring Cohort123

    Science.gov (United States)

    Lüneburg, Nicole; Xanthakis, Vanessa; Schwedhelm, Edzard; Sullivan, Lisa M.; Maas, Renke; Anderssohn, Maike; Riederer, Ulrich; Glazer, Nicole L.; Vasan, Ramachandran S.; Böger, Rainer H.

    2011-01-01

    l-Arginine, as a precursor of NO synthesis, has attracted much scientific attention in recent years. Experimental mouse models suggest that l-arginine supplementation can retard, halt, or even reverse atherogenesis. In human studies, supplementation with l-arginine improved endothelium-dependent vasodilation. However, l-arginine levels are best interpreted in the context of levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of NO synthase. Thus, reference limits for circulating l-arginine and the l-arginine:ADMA ratio may help to determine the nutritional state of individuals at high cardiovascular risk in light of increased ADMA levels. We defined reference limits for plasma l-arginine in 1141 people and for the l-arginine:ADMA ratio in 1138 relatively healthy individuals from the Framingham Offspring Cohort. Plasma l-arginine and ADMA concentrations were determined by using a stable isotope-based LC-MS/MS method. The reference limits (2.5th and 97.5th percentiles) for plasma l-arginine were 41.0 μmol/L (95% CI = 39.5–42.5 μmol/L) and 114 μmol/L (95% CI = 112–115 μmol/L), whereas corresponding reference limits (2.5th and 97.5th percentiles) for the l-arginine:ADMA ratio were 74.3 μmol/L (95% CI = 71.1–77.3 μmol/L) and 225 μmol/L (95% CI = 222–228 μmol/L). Plasma l-arginine was positively associated with the estimated glomerular filtration rate (eGFR) and blood glucose levels, whereas the l-arginine:ADMA ratio was positively associated with eGFR and diastolic blood pressure but inversely associated with homocysteine and (log)C-reactive protein. We report reference levels for plasma l-arginine and for the l-arginine:ADMA ratio that may be helpful for evaluation of the effects of l-arginine supplementation in participants with an impaired l-arginine/NO pathway. PMID:22031661

  15. The effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities.

    Science.gov (United States)

    Jabłecka, A; Bogdański, P; Balcer, N; Cieślewicz, A; Skołuda, A; Musialik, K

    2012-03-01

    Numerous studies indicate hyperglycemia and oxidative stress as factors responsible for endothelium dysfunction and the following development of angiopathy. Increased production of free radicals by vascular endothelium causes disturbance in production and/or decreases bioaccessibility of nitric oxide (NO). It has been suggested that L-arginine supplementation is a reasonable method to increase endothelium NO production and lower free radicals formation. There is a growing number of evidence showing that dietary supplementation of arginine reverses endothelial dysfunction associated with major cardiovascular risk factors and ameliorates many common cardiovascular disorders. The aim of the study was to evaluate the potential influence of two-months oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status (TAS). 38 patients with atherosclerotic peripheral arterial disease of lower extremities at Fontaine's stage II and coexisting type 2 diabetes and 12 healthy volunteers as control group were studied. All patients were treated with oral L-arginine (3 x 2 g/day) for two months. Fasting glucose, HbAlc, nitric oxide and total antioxidant status (TAS) were measured before and after the study. Fasting glucose and HbAlc did not change significantly after L-arginine treatment. Statistically significant increase in NO concentration and TAS level was found. Oral two-month supplementation with L-arginine (3 x 2 g/day) had no effect on fasting glucose and HbA1 level in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities at Fontaine's stage II. The supplementation of L-arginine led to substantial increase in NO concentration and TAS level in these patients, suggesting its indirect antioxidative effect.

  16. Chemical mechanisms of histone lysine and arginine modifications.

    Science.gov (United States)

    Smith, Brian C; Denu, John M

    2009-01-01

    Histone lysine and arginine residues are subject to a wide array of post-translational modifications including methylation, citrullination, acetylation, ubiquitination, and sumoylation. The combinatorial action of these modifications regulates critical DNA processes including replication, repair, and transcription. In addition, enzymes that modify histone lysine and arginine residues have been correlated with a variety of human diseases including arthritis, cancer, heart disease, diabetes, and neurodegenerative disorders. Thus, it is important to fully understand the detailed kinetic and chemical mechanisms of these enzymes. Here, we review recent progress towards determining the mechanisms of histone lysine and arginine modifying enzymes. In particular, the mechanisms of S-adenosyl-methionine (AdoMet) dependent methyltransferases, FAD-dependent demethylases, iron dependent demethylases, acetyl-CoA dependent acetyltransferases, zinc dependent deacetylases, NAD(+) dependent deacetylases, and protein arginine deiminases are covered. Particular attention is paid to the conserved active-site residues necessary for catalysis and the individual chemical steps along the catalytic pathway. When appropriate, areas requiring further work are discussed.

  17. Effect of iron, taurine and arginine on rat hepatic fibrosis

    International Nuclear Information System (INIS)

    Song Liangwen; Wang Dewen; Cui Xuemei

    1997-01-01

    Objective: The promotion role of iron on pathogenesis of hepatic fibrosis and the protective role of taurine and L-arginine against hepatic fibrosis were studied. Method: The model of rat radiation hepatic fibrosis was used. Experimental rats were divided into 0 Gy, 30 Gy, 30 Gy + iron, 30 Gy + taurine and 30 Gy + L-arginine groups. Serum iron, liver tissue hydroxyproline (Hyp) and malondialdehyde (MDA) were measured one and three months respectively after irradiation of hepatic tissue, production and distribution characteristics of hepatic tissue type I and III collagen were observed with a polarizing microscope. Results: Administration of iron agent could significantly increase hepatic tissue MDA content and serum iron concentration, one month after irradiation, hepatic tissue Hyp in 30 Gy + iron group began to increase, and collagen in hepatic tissue obviously increased. Taurine and L-arginine could reduce serum iron concentration and decrease production of hepatic fissure Hyp. Conclusion: Exogenous iron agent could promote early development of radiation hepatic fibrosis; taurine and arginine could diminish pathologic alteration of hepatic fibrosis to a certain extent

  18. Theoretical insights into catalytic mechanism of protein arginine methyltransferase 1.

    Directory of Open Access Journals (Sweden)

    Ruihan Zhang

    Full Text Available Protein arginine methyltransferase 1 (PRMT1, the major arginine asymmetric dimethylation enzyme in mammals, is emerging as a potential drug target for cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1 will facilitate inhibitor design. However, detailed mechanisms of the methyl transfer process and substrate deprotonation of PRMT1 remain unclear. In this study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation by employing molecular dynamics (MD simulation and quantum mechanics/molecular mechanics (QM/MM calculation. Ternary complex models, composed of PRMT1, peptide substrate, and S-adenosyl-methionine (AdoMet as cofactor, were constructed and verified by 30-ns MD simulation. The snapshots selected from the MD trajectory were applied for the QM/MM calculation. The typical SN2-favored transition states of the first and second methyl transfers were identified from the potential energy profile. Deprotonation of substrate arginine occurs immediately after methyl transfer, and the carboxylate group of E144 acts as proton acceptor. Furthermore, natural bond orbital analysis and electrostatic potential calculation showed that E144 facilitates the charge redistribution during the reaction and reduces the energy barrier. In this study, we propose the detailed mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on the small-molecule effectors design, and enables further investigations into the physiological function of this family.

  19. Arginine-dependent acid resistance in Salmonella enterica serovar Typhimurium

    NARCIS (Netherlands)

    Kieboom, J.; Abee, T.

    2006-01-01

    Salmonella enterica serovar Typhimurium does not survive a pH 2.5 acid challenge under conditions similar to those used for Escherichia coli (J. W. Foster, Nat. Rev. Microbiol. 2:898-907, 2004). Here, we provide evidence that S. enterica serovar Typhimurium can display arginine-dependent acid

  20. Arginine and Citrulline for the Treatment of MELAS Syndrome

    Directory of Open Access Journals (Sweden)

    Ayman W. El-Hattab MD, FACMG

    2017-03-01

    Full Text Available Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes’ aspects of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome.

  1. l-Arginine is a Radioprotector for Hematopoietic Progenitor Cells

    Science.gov (United States)

    Pearce, Linda L.; Zheng, Xichen; Martinez-Bosch, Sandra; Kerr, Patrick P.; Khlangwiset, Pornsri; Epperly, Michael W.; Fink, Mitchell P.; Greenberger, Joel S.; Peterson, Jim

    2012-01-01

    l-Arginine is shown to protect hematopoietic progenitor (32D cl 3) cells from death due to exposure to γ radiation (137Cs). Some of the other intermediates in the urea cycle, namely ornithine and citrulline, plus urea itself, were not found to have any significant impact on cell survival after irradiation. Intriguingly, supplementation of irradiated cells with l-arginine results in decreased production of peroxynitrite, suggesting that suppression of superoxide generation by nitric oxide synthase in one or more microenvironments is an important factor in the observed radioprotection. The absence of any radioprotective effect of l-arginine in cells at 3% oxygen also confirms the involvement of one or more oxygen-derived species. Knockdown experiments with nitric oxide synthase (NOS) siRNAs in cells and NOS knockout animals confirm that the observed radioprotection is associated with nNOS (NOS-1). l-Arginine also ameliorates the transient inhibition of the electron-transport chain complex I that occurs within 30 min of completing the dose (10 Gy) and that appears to be a functional marker for postirradiation mitochondrial oxidant production. PMID:22175298

  2. Twin-arginine-dependent translocation of folded proteins

    Science.gov (United States)

    Fröbel, Julia; Rose, Patrick; Müller, Matthias

    2012-01-01

    Twin-arginine translocation (Tat) denotes a protein transport pathway in bacteria, archaea and plant chloroplasts, which is specific for precursor proteins harbouring a characteristic twin-arginine pair in their signal sequences. Many Tat substrates receive cofactors and fold prior to translocation. For a subset of them, proofreading chaperones coordinate maturation and membrane-targeting. Tat translocases comprise two kinds of membrane proteins, a hexahelical TatC-type protein and one or two members of the single-spanning TatA protein family, called TatA and TatB. TatC- and TatA-type proteins form homo- and hetero-oligomeric complexes. The subunits of TatABC translocases are predominantly recovered from two separate complexes, a TatBC complex that might contain some TatA, and a homomeric TatA complex. TatB and TatC coordinately recognize twin-arginine signal peptides and accommodate them in membrane-embedded binding pockets. Advanced binding of the signal sequence to the Tat translocase requires the proton-motive force (PMF) across the membranes and might involve a first recruitment of TatA. When targeted in this manner, folded twin-arginine precursors induce homo-oligomerization of TatB and TatA. Ultimately, this leads to the formation of a transmembrane protein conduit that possibly consists of a pore-like TatA structure. The translocation step again is dependent on the PMF. PMID:22411976

  3. Crystal structure of arginine methyltransferase 6 from Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Chongyuan Wang

    Full Text Available Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6 is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH. The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

  4. Analysis of an Alanine/Arginine Mixture by Using TLC/FTIR Technique

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2014-01-01

    Full Text Available We applied TLC/FTIR coupled with mapping technique to analyze an alanine/arginine mixture. Narrow band TLC plates prepared by using AgI as a stationary phase were used to separate alanine and arginine. The distribution of alanine and arginine spots was manifested by a 3D chromatogram. Alanine and arginine can be successfully separated by the narrow band TLC plate. In addition, the FTIR spectra of the separated alanine and arginine spots on the narrow band TLC plate are roughly the same as the corresponding reference IR spectra.

  5. Effect of methylation on the side-chain pKa value of arginine.

    Science.gov (United States)

    Evich, Marina; Stroeva, Ekaterina; Zheng, Yujun George; Germann, Markus W

    2016-02-01

    Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 ± 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition. © 2015 The Protein Society.

  6. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability.

    Science.gov (United States)

    Morita, Masahiko; Hayashi, Toshio; Ochiai, Masayuki; Maeda, Morihiko; Yamaguchi, Tomoe; Ina, Koichiro; Kuzuya, Masafumi

    2014-11-07

    Chronic supplementation with L-citrulline plus L-arginine has been shown to exhibit anti-atherosclerotic effects. However, the short-term action of this combination on the nitric oxide (NO)-cGMP pathway remains to be elucidated. The objective of the present study was to investigate the acute effects of a combination of oral L-citrulline and L-arginine on plasma L-arginine and NO levels, as well as on blood circulation. Rats or New Zealand white rabbits were treated orally with L-citrulline, or L-arginine, or a combination of each at half dosage. Following supplementation, plasma levels of L-arginine, NOx, cGMP and changes in blood circulation were determined sequentially. L-Citrulline plus L-arginine supplementation caused a more rapid increase in plasma L-arginine levels and marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids. Blood flow in the central ear artery in rabbits was also significantly increased by L-citrulline plus L-arginine administration as compared with the control. Our data show for the first time that a combination of oral L-citrulline and L-arginine effectively and rapidly augments NO-dependent responses at the acute stage. This approach may have clinical utility for the regulation of cardiovascular function in humans. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase.

    Science.gov (United States)

    Song, Wei; Sun, Xia; Chen, Xiulai; Liu, Dongxu; Liu, Liming

    2015-08-20

    In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline. Copyright © 2015. Published by Elsevier B.V.

  8. Enthalpy-driven interactions with sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Nadai, Ryo; Kimura, Hitoshi; Nishitsuji, Kazuchika; Uchimura, Kenji; Sakai-Kato, Kumiko; Kawakami, Kohsaku; Shigenaga, Akira; Kawakami, Toru; Otaka, Akira; Hojo, Hironobu; Sakashita, Naomi; Saito, Hiroyuki

    2016-06-01

    The first step of cell membrane penetration of arginine peptides is thought to occur via electrostatic interactions between positive charges of arginine residues and negative charges of sulfated glycosaminoglycans (GAGs) on the cell surface. However, the molecular interaction of arginine peptides with GAG still remains unclear. Here, we compared the interactions of several arginine peptides of Tat, R8, and Rev and their analogues with heparin in relation to the cell membrane penetration efficiency. The high-affinity binding of arginine peptides to heparin was shown to be driven by large favorable enthalpy contributions, possibly reflecting multidentate hydrogen bondings of arginine residues with sulfate groups of heparin. Interestingly, the lysine peptides in which all arginine residues are substituted with lysine residues exhibited negligible binding enthalpy despite of their considerable binding to heparin. In CHO-K1 cells, arginine peptides exhibited a great cell-penetrating ability whereas their corresponding lysine peptides did not penetrate into cells. The degree of cell penetration of arginine peptides markedly decreased by the chlorate treatment of cells which prevents the sulfation of GAG chains. Significantly, the cell penetration efficiency of arginine peptides was found to be correlated with the favorable enthalpy of binding to heparin. These results suggest that the enthalpy-driven strong interaction with sulfated GAGs such as heparan sulfate plays a critical role in the efficient cell membrane penetration of arginine peptides. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Role of arginine and its methylated derivatives in cancer biology and treatment

    Directory of Open Access Journals (Sweden)

    Tyihák Erno

    2001-12-01

    Full Text Available Abstract Both L-arginine supplementation and deprivation influence cell proliferation. The effect of high doses on tumours is determined by the optical configuration: L-arginine is stimulatory, D-arginine inhibitory. Arginine-rich hexapeptides inhibited tumour growth. Deprivation of L-arginine from cell cultures enhanced apoptosis. The pro-apoptotic action of NO synthase inhibitors, like NG-monomethyl-L-arginine, is manifested through inhibition of the arginase pathway. NG-hydroxymethyl-L-arginines caused apoptosis in cell cultures and inhibited the growth of various transplantable mouse tumours. These diverse biological activities become manifest through formaldehyde (HCHO because guanidine group of L-arginine in free and bound form can react rapidly with endogenous HCHO, forming NG-hydroxymethylated derivatives. L-arginine is a HCHO capturer, carrier and donor molecule in biological systems. The role of formaldehyde generated during metabolism of NG-methylated and hydroxymethylated arginines in cell proliferation and death can be shown. The supposedly anti-apoptotic homozygous Arg 72-p53 genotype may increase susceptibility of some cancers. The diverse biological effects of L-arginine and its methylated derivatives call for further careful studies on their possible application in chemoprevention and cancer therapy.

  10. Arginine: New Insights into Growth Performance and Urinary Metabolomic Profiles of Rats

    Directory of Open Access Journals (Sweden)

    Guangmang Liu

    2016-08-01

    Full Text Available Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through 1H-NMR spectroscopy. Twenty rats were randomly assigned to two groups supplemented with 0% or 1.0% l-arginine for 4 weeks. Urine samples were analyzed through NMR-based metabolomics. Arginine supplementation significantly increased the urine levels of 4-aminohippurate, acetate, creatine, creatinine, ethanolamine, formate, hippurate, homogentisate, indoxyl sulfate, and phenylacetyglycine. Conversely, arginine decreased the urine levels of acetamide, β-glucose, cirtulline, ethanol, glycine, isobutyrate, lactate, malonate, methymalonate, N-acetylglutamate, N-methylnicotinamide, and propionate. Results suggested that arginine can alter common systemic metabolic processes, including energy metabolism, amino acid metabolism, and gut microbiota metabolism. Moreover, the results also imply a possible physiological role of the metabolism in mediating the arginine supplementation-supported growth of rats.

  11. Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

    Science.gov (United States)

    It is not known whether arginine homeostasis is negatively affected by a "long-term" dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healt...

  12. Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

    Science.gov (United States)

    Stadelmann, Britta; Merino, María C; Persson, Lo; Svärd, Staffan G

    2012-01-01

    In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that

  13. Exercise training reverses the negative effects of chronic L-arginine supplementation on insulin sensitivity.

    Science.gov (United States)

    Salgueiro, Rafael Barrera; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Castro Barbosa, Thais; Nunes, Maria Tereza

    2017-12-15

    L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal secretion. However, the chronic consumption of arginine has been shown to impair insulin sensitivity. In the present study, we aimed to evaluate whether chronic arginine supplementation associated with exercise training would have a beneficial impact on insulin sensitivity. We, therefore, treated Wistar rats for 4weeks with arginine, associated or not with exercise training (treadmill). We assessed the somatotropic activation, by evaluating growth hormone (GH) gene expression and protein content in the pituitary, as well is GH concentration in the serum. Additionally, we evaluate whole-body insulin sensitivity, by performing an insulin tolerance test. Skeletal muscle morpho-physiological parameters were also assessed. Insulin sensitivity was impaired in the arginine-treated rats. However, exercise training reversed the negative effects of arginine. Arginine and exercise training increased somatotropic axis function, muscle mass and body weight gain. The combination arginine and exercise training further decreased total fat mass. Our results confirm that chronic arginine supplementation leads to insulin resistance, which can be reversed in the association with exercise training. We provide further evidence that exercise training is an important tool to improve whole-body metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Arginine decarboxylase as the source of putrescine for tobacco alkaloids

    Science.gov (United States)

    Tiburcio, A. F.; Galston, A. W.

    1986-01-01

    The putrescine which forms a part of nicotine and other pyrrolidine alkaloids is generally assumed to arise through the action of ornithine decarboxylase (ODC). However, we have previously noted that changes in the activity of arginine decarboxylase (ADC), an alternate source of putrescine, parallel changes in tissue alkaloids, while changes in ODC activity do not. This led us to undertake experiments to permit discrimination between ADC and ODC as enzymatic sources of putrescine destined for alkaloids. Two kinds of evidence presented here support a major role for ADC in the generation of putrescine going into alkaloids: (a) A specific 'suicide inhibitor' of ADC effectively inhibits the biosynthesis of nicotine and nornicotine in tobacco callus, while the analogous inhibitor of ODC is less effective, and (b) the flow of 14C from uniformly labelled arginine into nicotine is much more efficient than that from ornithine.

  15. l-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors.

    Science.gov (United States)

    Deveaux, Ambre; Pham, Isabelle; West, Sheila G; André, Etienne; Lantoine-Adam, Frédérique; Bunouf, Pierre; Sadi, Samira; Hermier, Dominique; Mathé, Véronique; Fouillet, Hélène; Huneau, Jean-François; Benamouzig, Robert; Mariotti, François

    2016-07-01

    Vascular endothelial dysfunction, the hallmark of early atherosclerosis, is induced transiently by a high-fat meal. High doses of free l-arginine supplements reduce fasting endothelial dysfunction. We sought to determine the effects of a low dose of a sustained-release (SR) l-arginine supplement on postprandial endothelial function in healthy overweight adults with cardiometabolic risk factors and to investigate whether this effect may vary by baseline arginine status. In a randomized, double-blind, 2-period crossover, placebo-controlled trial (4-wk treatment, 4-wk washout), we compared the effects of 1.5 g SR-l-arginine 3 times/d (4.5 g/d) with placebo in 33 healthy overweight adults [body mass index (BMI, in kg/m(2)): 25 to >30] with the hypertriglyceridemic waist (HTW) phenotype [plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)]. The main outcome variable tested was postprandial endothelial function after a high-fat meal (900 kcal), as evaluated by use of flow-mediated dilation (FMD) and Framingham reactive hyperemia index (fRHI), after each treatment. By use of subgroup analysis, we determined whether the effect was related to the baseline plasma arginine concentration. In the total population, the effects of SR-arginine supplementation on postprandial endothelial function were mixed and largely varied with baseline fasting arginine concentration (P-interaction supplementation attenuated the postprandial decrease in both FMD (29% decrease with SR-arginine compared with 50% decrease with placebo) and fRHI (5% increase with SR-arginine compared with 49% decrease with placebo), resulting in significantly higher mean ± SEM values with SR-arginine (FMD: 4.0% ± 0.40%; fRHI: 0.41 ± 0.069) than placebo (FMD: 2.9% ± 0.31%; fRHI: 0.21 ± 0.060) at the end of the postprandial period (P Supplementation with low-dose SR-arginine alleviates postprandial endothelial dysfunction in healthy HTW adults when the baseline plasma arginine

  16. PRMT1-mediated arginine methylation controls ATXN2L localization

    Energy Technology Data Exchange (ETDEWEB)

    Kaehler, Christian; Guenther, Anika; Uhlich, Anja; Krobitsch, Sylvia, E-mail: krobitsc@molgen.mpg.de

    2015-05-15

    Arginine methylation is a posttranslational modification that is of importance in diverse cellular processes. Recent proteomic mass spectrometry studies reported arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a protein that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. Here, we investigated the methylation state of ATXN2L and its significance for ATXN2L localization. We first confirmed that ATXN2L is asymmetrically dimethylated in vivo, and observed that the nuclear localization of ATXN2L is altered under methylation inhibition. We further discovered that ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). Finally, we showed that neither mutation of the arginine–glycine-rich motifs of ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules, suggesting that methylation of ATXN2L is probably not mandatory. - Highlights: • ATXN2L is asymmetrically dimethylated in vivo. • ATXN2L interacts with PRMT1 under normal and stress conditions. • PRMT1-mediated dimethylation of ATXN2L controls its nuclear localization. • ATXN2L localization to stress granules appears independent of its methylation state.

  17. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    -induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...... and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion...

  18. Does an ‘L-arginine doped orthophosphoric acid’ crystal exist?

    Energy Technology Data Exchange (ETDEWEB)

    Srinivasan, Bikshandarkoil R., E-mail: srini@unigoa.ac.in

    2014-04-15

    The reactive nature of aqueous orthophosphoric acid (H{sub 3}PO{sub 4}) towards L-arginine (L-Arg), to form a phosphate salt namely L-arginine phosphate monohydrate (LAP), rules out the doping of any L-arginine into H{sub 3}PO{sub 4}. Hence, the reported claim of growth of ‘L-arginine doped orthophosphoric acid’ crystals by Saradha et al. J. Lumin (2013) is untenable. -- Highlights: • Orthophosphoric acid (H{sub 3}PO{sub 4}) is a tetrahedral molecule. • Aqueous H{sub 3}PO{sub 4} reacts with L-arginine to form mono- or bis-dihydrogenphosphate salt. • L-arginine doped orthophosphoric acid crystal does not exist.

  19. Clinical effectiveness of exogenous L-arginine in patients with coronary heart disease after community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    T. O. Kulynych

    2017-02-01

    Full Text Available Coronary heart disease and community acquired pneumonia associated with a higher risk for morbidity and mortality. The optimization of treatment of comorbid pathology by medicines which modify endothelium functional state is important. Aim: to study effect of exogenous L-arginine on clinical course of disease, markers of systemic inflammation and endothelial dysfunction in patients with coronary heart disease (CHD and community-acquired pneumonia (CAP. Materials and methods. 60 patients with CHD and CAP (the median 72.50 years, range 66.00; 75.00 were included into the study. Patients were randomized in 2 groups: first – 30 patients with basic therapy combined with L-arginine; and second – 30 patients with basic therapy. hs-CRP, neopterin, РАРР-А, NT-proBNP were measured by ELISA-TEST before treatment and 1 month after. Clinical course was assessed during 1 year of follow-up. Results. In the first group the hospitalization rate due to CHD and heart failure decompensation was significantly rare. Biomarkers changes in the 1st group were significant: hs-CRP was significantly decreased by 57.14 % (in the 2nd group – by 28.57 %; neopterin – by 36.57 % (in the 2nd group – by 20.91 %; РАРР-А – by 35.71 % (in the 2nd group – by 4.76 %. There was revealed a significant decreasing of NT-proBNP levels in patients receiving L-arginine by comparing with basic therapy: with the I stage of heart failure (HF – by 50.97 % vs 21.82 %, with the II-A stage of HF – by 43.82 % vs 5.61 % (p < 0.05. After 1 month of therapy patients from the 1st group had significantly lower rates of neopterin – by 16.46 %, and NT-proBNP – by 40.92 % in the subgroup of patients with II-A stage of HF (p < 0.05 compared with patients who received only the basic therapy. Conclusions. Combination of exogenous L-arginine and basic therapy in patients with CHD and CAP was associated with benign clinical course and positive changes of endothelium functional

  20. A novel L-arginine salt nonlinear optical crystal: L-arginine p-nitrobenzoate monohydrate (LANB)

    Science.gov (United States)

    Wang, L.; Zhang, G. H.; Liu, X. T.; Wang, L. N.; Wang, X. Q.; Zhu, L. Y.; Xu, D.

    2014-01-01

    A novel L-arginine salt nonlinear optical single crystal, L-arginine p-nitrobenzoate monohydrate (LANB) has been grown by slow cooling method from aqueous solution. Its solubility at different temperatures in water was measured. The grown crystal was characterized by the elemental analyses, X-ray single crystal and powder diffractions, Fourier transform infrared and Raman spectra. The structure analysis revealed that LANB belongs to the monoclinic crystallographic system, space group P21, with unit cell parameters: a = 8.566(3), b = 5.817(2), c = 17.131(7) Å, β = 101.223(5)°, Z = 2 and V = 837.2(6) Å3. The proton and carbon configurations of L-arginine were confirmed through 1H NMR and 13C NMR spectra analyses. The linear and nonlinear optical properties of LANB crystal were studied by the use of transmission spectrum and second harmonic generation (SHG). The thermal properties were investigated by using thermo gravimetric (TG) and differential thermal analysis (DTA).

  1. The arginine-ornithine antiporter ArcD contributes to biological fitness of Streptococcus suis

    Directory of Open Access Journals (Sweden)

    Marcus eFulde

    2014-08-01

    Full Text Available The arginine-ornithine antiporter (ArcD is part of the Arginine Deiminase System (ADS, a catabolic, energy-providing pathway found in a variety of different bacterial species, including the porcine zoonotic pathogen Streptococcus suis. The ADS has recently been shown to play a role in the pathogenicity of S. suis, in particular in its survival in host cells. The contribution of arginine and arginine transport mediated by ArcD, however, has yet to be clarified. In the present study, we showed by experiments using [U-13C6]arginine as a tracer molecule that S. suis is auxotrophic for arginine and that bacterial growth depends on the uptake of extracellular arginine. To further study the role of ArcD in arginine metabolism, we generated an arcD-specific mutant strain and characterized its growth compared to the wild-type (WT strain, a virulent serotype 2 strain. The mutant strain showed a markedly reduced growth rate in chemically defined media supplemented with arginine when compared to the WT strain, indicating that ArcD promotes arginine uptake. To further evaluate the in vivo relevance of ArcD, we studied the intracellular bacterial survival of the arcD mutant strain in an epithelial cell culture infection model. The mutant strain was substantially attenuated, and its reduced intracellular survival rate correlated with a lower ability to neutralize the acidified environment. Based on these results, we propose that ArcD, by its function as an arginine-ornithine antiporter, is important for supplying arginine as substrate of the ADS and, thereby, contributes to biological fitness and virulence of S. suis in the host.

  2. Effects of L-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia.

    Science.gov (United States)

    Poeze, Martijn; Bruins, Maaike J; Kessels, Fons; Luiking, Yvette C; Lamers, Wouter H; Deutz, Nicolaas E P

    2011-06-01

    Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. The objective was to evaluate the effects of l-arginine pretreatment on arginine-nitric oxide (NO) production and hepatosplanchnic perfusion during subsequent endotoxemia. In a randomized controlled trial, pigs (20-25 kg) received 3 μg . kg(-1) . min(-1) lipopolysaccharide (LPS; 5 endotoxin units/ng) intravenously and saline resuscitation. l-Arginine (n = 8; 5.3 μmol . kg(-1) . min(-1)) or saline (n = 8) was infused starting 12 h before LPS infusion and continued for 24 h after the endotoxin infusion ended. Whole-body appearance rates, portal-drained viscera (PDV), and liver fluxes of arginine, citrulline, NO, and arginine de novo synthesis were measured by using stable-isotope infusion of [(15)N(2)]arginine and [(13)C-(2)H(2)]citrulline. Hepatosplanchnic perfusion was assessed by using a primed continuous infusion of para-aminohippuric acid and jejunal intramucosal partial pressure of carbon dioxide and was related to systemic hemodynamics. Arginine supplementation before LPS increased whole-body NO production in the PDV but not in the liver. Furthermore, it increased blood flow in the portal vein but not in the aorta and hepatic artery. During endotoxin infusion, arginine pretreatment was associated with an increased whole-body arginine appearance and NO production in the gut. Additional effects included a preserved mean arterial pressure, the prevention of an increase in pulmonary arterial pressure, an attenuated metabolic acidosis, and an attenuated increase in the intramucosal partial pressure of carbon dioxide. Arginine treatment starting before endotoxemia appears to be beneficial because it improves hepatosplanchnic perfusion and oxygenation during prolonged endotoxemia, probably through an enhancement in NO synthesis, without causing deleterious systemic side effects.

  3. Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test

    OpenAIRE

    Tschuor, F

    2011-01-01

    Background: Responsiveness of β-cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. Hypothesis: Diabetic cats with and without remission will have different arginine-induced insulin or glucagon response. Animals: 17 cats with diabetes, 7 healthy cats. Methods: Response to IVAST was assessed by calculating insulin and glucagon area under the c...

  4. Safety of long-term dietary supplementation with L-arginine in pigs.

    Science.gov (United States)

    Hu, Shengdi; Li, Xilong; Rezaei, Reza; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

    2015-05-01

    This study was conducted with a swine model to determine the safety of long-term dietary supplementation with L-arginine-HCl or L-arginine free base. Beginning at 30 days of age, pigs were fed a corn- and soybean meal-based diet (31.5 g/kg body weight/day) supplemented with 0, 1.21, 1.81 or 2.42 % L-arginine-HCl (Experiment 1) or with 0, 1, 1.5 or 2 % L-arginine (Experiment 2). The supplemental doses of 0, 1, 1.5, and 2 % L-arginine provided pigs with 0, 315, 473, and 630 mg L-arginine/kg body weight/day, respectively, which were equivalent to 0, 286, 430, and 573 mg L-arginine/kg body weight/day, respectively, in humans. At 121 days of age (91 days after initiation of supplementation), blood samples were obtained from the jugular vein of pigs at 1 and 4 h after feeding for hematological and clinical chemistry tests. Dietary supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, albumin and reticulocytes, while reducing plasma concentrations of ammonia, free fatty acids, triglyceride, cholesterol, and neutrophils. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Other variables in standard hematology and clinical chemistry tests, serum concentrations of insulin, growth hormone and insulin-like growth factor-I did not differ among all the groups of pigs. These results indicate that dietary supplementation with L-arginine (up to 630 mg/kg body weight/day) is safe in pigs for at least 91 days. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.

  5. Oral L-arginine supplementation impacts several reproductive parameters during the postpartum period in mares.

    Science.gov (United States)

    Kelley, Dale E; Warren, Lori K; Mortensen, Christopher J

    2013-05-01

    L-arginine is an amino acid which can alter pituitary function and increase blood flow to the reproductive tract. The objective was to determine the effect of supplementing 100g of L-arginine on plasma arginine concentrations, follicular dynamics and ovarian and uterine artery blood flow during the estrus that occurs subsequent to foaling. In Experiment 1, mares were fed 100g L-arginine for 1 day during the last 3 weeks of pregnancy and plasma samples taken for every hour for the first 4h and every other hour until 12h.L-arginine supplementation elevated plasma arginine concentrations from 1 to 8h post feeding; arginine peaked at 6h (arginine: 515±33μmol/L; control: 80±33μmol/L). In Experiment 2, mares received either 100g L-arginine or control diets beginning 21 d before the expected foaling date and continued for 30 d postpartum. The reproductive tract was evaluated by transrectal Doppler ultrasonography from Day 1 postpartum through Day 30. There were no differences in ovarian follicular dynamics, ovarian or uterine resistance indices between groups. Vascular perfusion of the F1 follicular wall was greater in L-arginine supplemented mares (37.3±2.6%) than controls (25.4±2.7%; PL-arginine supplemented mares had a smaller uterine body and horns and accumulated less uterine fluid than controls (PL-arginine supplementation as a breeding management tool during the postpartum period to increase reproductive success. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

    Science.gov (United States)

    Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

    2017-07-01

    Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

  7. l-Arginine modulates neonatal lymphocyte proliferation through an interleukin-2 independent pathway

    Science.gov (United States)

    Yu, Hong-Ren; Kuo, Ho-Chang; Huang, Li-Tung; Chen, Chih-Cheng; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Huang, Hsin-Chun; Yang, Kuender D; Ou, Chia-Yo; Hsu, Te-Yao

    2014-01-01

    In cases of arginine depletion, lymphocyte proliferation, cytokine production and CD3ζ chain expression are all diminished. In addition to myeloid suppressor cells, polymorphonuclear cells (PMN) also exert T-cell immune suppressive effects through arginase-induced l-arginine depletion, especially during pregnancy. In this study, we investigated how arginase/l-arginine modulates neonatal lymphocyte proliferation. Results showed that the neonatal plasma l-arginine level was lower than in adults (48·1 ± 11·3 versus 86·5 ± 14·6 μm; P = 0·003). Neonatal PMN had a greater abundance of arginase I protein than adult PMN. Both transcriptional regulation and post-transcriptional regulation were responsible for the higher arginase I expression of neonatal PMN. Exogenous l-arginine enhanced neonate lymphocyte proliferation but not that of adult cells. The RNA-binding protein HuR was important but was not the only modulation factor in l-arginine-regulated neonatal T-cell proliferation. l-Arginine-mediated neonatal lymphocyte proliferation could not be blocked by interleukin-2 receptor blocking antibodies. These results suggest that the altered arginase/l-arginine cascade may be one of the mechanisms that contribute to altered neonatal immune responses. Exogenous l-arginine could enhance neonate lymphocyte proliferation through an interleukin-2-independent pathway. PMID:24697328

  8. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia.

    Science.gov (United States)

    Jaja, S I; Ogungbemi, S O; Kehinde, M O; Anigbogu, C N

    2016-06-01

    The effect of l-arginine on liver function in SCD has received little or no attention. The effect of a chronic, oral, low-dose supplementation with l-arginine (1gm/day for 6 weeks) on some liver enzymes, lipid peroxidation and nitric oxide metabolites was studied in 20 normal (non-sickle cell anaemia; NSCA) subjects and 20 sickle cell anaemia (SCA) subjects. Ten milliliters of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP), plasma total bilirubin concentration [TB], malondialdehyde concentration [MDA] and nitric oxide metabolites concentration [NOx]. Before supplementation, ALT, AST, ALP (pSupplementation caused greater percent increases in [R], and [NOX] in SCA than in NSCA subjects (pl-Arginine caused greater percent reductions in ALT and AST in SCA subjects but greater percent reduction in ALP in NSCA subjects (psupplementation with l-arginine improved liver function, oxidative stress, plasma arginine concentration and nitric oxide metabolites levels in NSCA and SCA subjects. Responses in SCA subjects to l-arginine were more sensitive than in NSCA subjects. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. L-Arginine oxidase from Pseudomonas sp. TPU 7192: Characterization, gene cloning, heterologous expression, and application to L-arginine determination.

    Science.gov (United States)

    Matsui, Daisuke; Terai, Anna; Asano, Yasuhisa

    2016-01-01

    L-Arginine oxidase (AROD, EC 1.4.3.-) was discovered in newly discovered Pseudomonas sp. TPU 7192 and its characteristics were described. The molecular mass (MS) of the enzyme was estimated to be 528 kDa, which was accounted for by eight identical subunits with MS of 66 kDa each. AROD was identified as a flavin adenine dinucleotide (FAD)-dependent enzyme with 1 mol of FAD being contained in each subunit. It catalyzed the oxidative deamination of L-arginine and converted L-arginine to 2-ketoarginine, which was non-enzymatically converted into 4-guanidinobutyric acid when the hydrogen peroxide (H2O2) formed by L-arginine oxidation was not removed. In contrast, 2-ketoarginine was present when H2O2was decomposed. AROD was specific to L-arginine with a Km value of 149 μM. It exhibited maximal activity at 55 °C and pH 5.5. AROD was stable in the pH range 5.5-7.5 and >95% of its original activity was below 60 °C at pH 7.0. Since these enzymatic properties are considered suitable for the determination of L-arginine, the gene was cloned and expressed in a heterologous expression system. We herein successfully developed a new simple enzymatic method for the determination of L-arginine using Pseudomonas AROD. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Oral L-arginine supplementation in patients with mild arterial hypertension and its effect on plasma level of asymmetric dimethylarginine, L-citruline, L-arginine and antioxidant status.

    Science.gov (United States)

    Jabecka, A; Ast, J; Bogdaski, P; Drozdowski, M; Pawlak-Lemaska, K; Cielewicz, A R; Pupek-Musialik, D

    2012-11-01

    Potential role of L-arginine supplementation as a new effective strategy of improving endothelial function in patients with hypertension is recently under consideration. To evaluate influence of 28-day oral supplementation of L-arginine on plasma level of asymmetric dimethylarginine (ADMA), L-citrulline, L-arginine and total antioxidant status (TAS), in patients with mild arterial hypertension. 54 participants (24 women and 30 men) were studied. Ambulatory blood pressure monitoring (ABPM) was used for allotting patients to either healthy control group (19 subjects) or hypertensive treatment group (35 patients). Patients were later randomized to either L-arginine (2 g tid or 4 g tid) or placebo. During 28 days of study on 5 consecutive visits TAS, plasma level of ADMA, L-citrulline, and L-arginine were measured. In patients with mild hypertension treated with L-arginine significant increase in TAS and plasma level of arginine and citrulline was observed. Additionally plasma ADMA concentrations after 28 days of L-arginine supplementation significantly exceeded initial concentrations. L-arginine supplementation increases plasma arginine, citrulline and TAS in patients with mild arterial hypertension. It confirms the thesis that augmented concentrations of L-arginine stimulate NO biosynthesis which leads to reduction of oxidative stress. Increase of ADMA plasma level after L-arginine supplementation confirms correlation between ADMA and L-arginine.

  11. 8-year retrospective analysis of intravenous arginine therapy for acute metabolic strokes in pediatric mitochondrial disease.

    Science.gov (United States)

    Ganetzky, Rebecca D; Falk, Marni J

    2018-03-01

    Intravenous (IV) arginine has been reported to ameliorate acute metabolic stroke symptoms in adult patients with Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes (MELAS) syndrome, where its therapeutic benefit is postulated to result from arginine acting as a nitric oxide donor to reverse vasospasm. Further, reduced plasma arginine may occur in mitochondrial disease since the biosynthesis of arginine's precursor, citrulline, requires ATP. Metabolic strokes occur across a wide array of primary mitochondrial diseases having diverse molecular etiologies that are likely to share similar pathophysiologic mechanisms. Therefore, IV arginine has been increasingly used for the acute clinical treatment of metabolic stroke across a broad mitochondrial disease population. We performed retrospective analysis of a large cohort of subjects who were under 18 years of age at IRB #08-6177 study enrollment and had molecularly-confirmed primary mitochondrial disease (n = 71, excluding the common MELAS m.3243A>G mutation). 9 unrelated subjects in this cohort received acute arginine IV treatment for one or more stroke-like episodes (n = 17 total episodes) between 2009 and 2016 at the Children's Hospital of Philadelphia. Retrospectively reviewed data included subject genotype, clinical symptoms, age, arginine dosing, neuroimaging (if performed), prophylactic therapies, and adverse events. Genetic etiologies of subjects who presented with acute metabolic strokes included 4 mitochondrial DNA (mtDNA) pathogenic point mutations, 1 mtDNA deletion, and 4 nuclear gene disorders. Subject age ranged from 19 months to 23 years at the time of any metabolic stroke episode (median, 8 years). 3 subjects had recurrent stroke episodes. 70% of subjects were on prophylactic arginine or citrulline therapy at the time of a stroke-like episode. IV arginine was initiated on initial presentation in 65% of cases. IV arginine was given for 1-7 days (median, 1 day). A

  12. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The manganese (II), cobalt (II), nickel (II) and copper (II) complexes of N, N' – bis(benzoin)ethylenediiminato have been prepared and characterized by infrared, elemental analysis, conductivity measurements and solubility. The potentiometric, and elemental analyses studies of the complexes revealed 1:1 ...

  13. Exercise-induced Protein Arginine Methyltransferase Expression in Skeletal Muscle.

    Science.gov (United States)

    Vanlieshout, Tiffany L; Stouth, Derek W; Tajik, Tania; Ljubicic, Vladimir

    2018-03-01

    This study aimed to determine protein arginine methyltransferase 1 (PRMT1), -4 (also known as coactivator-associated arginine methyltransferase 1 [CARM1]), and -5 expression and function during acute, exercise-induced skeletal muscle remodeling in vivo. C57BL/6 mice were assigned to one of three experimental groups: sedentary, acute bout of exercise, or acute exercise followed by 3 h of recovery. Mice in the exercise groups performed a single bout of treadmill running at 15 m·min for 90 min. Hindlimb muscles were collected, and quantitative real-time polymerase chain reaction and Western blotting were used to examine exercise-induced gene expression. The PRMT gene expression and global enzyme activity were muscle-specific, generally being higher (P < 0.05) in slow, oxidative muscle, as compared with faster, more glycolytic tissue. Despite the significant activation of canonical exercise-induced signaling involving AMP-activated protein kinase and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), PRMT expression and activity at the whole muscle level were unchanged. However, subcellular analyses revealed a significant exercise-evoked myonuclear translocation of PRMT1 before the nuclear accumulation of PGC-1α. Acute physical activity also augmented (P < 0.05) the targeted methyltransferase activities of the PRMT in the myonuclear compartment, suggesting that PRMT-mediated histone arginine methylation is part of the early signals that drive muscle plasticity. Finally, basal PGC-1α asymmetric dimethylarginine status, as well as constitutive interactions between PGC-1α and PRMT1 or CARM1 may contribute to the exercise-induced muscle remodeling process. The present study provides the first evidence that PRMT activity is selectively augmented during the initial activation of exercise-induced skeletal muscle remodeling in vivo. These data support the emergence of PRMTs as important players in the regulation of skeletal muscle plasticity.

  14. Effects of arginine and phytogenic additive supplementation on performance and health of brown-egg layers

    Directory of Open Access Journals (Sweden)

    Vitor Barbosa Fascina

    Full Text Available ABSTRACT This study was performed to evaluate the effects of the association of different digestible arginine and phytogenic additive dietary levels on performance and health status of brown-egg layers. In this study, a total of 504 33-week-old Hisex Brown layers were distributed into a completely randomized experimental design to a 4 × 3 factorial arrangement (dietary digestible arginine levels: 880, 968, 1056, or 1144 mg/kg of feed × phytogenic additive levels: 0, 100, and 200 mg/kg of feed with six replicate cages of seven birds per cage. The phytogenic additive was composed of extracts of Baccharis dracunculifolia (40%, Astragalus membranaceus lipopolysaccharides (20%, cinnamon, and grape seed (20%. Feed intake was reduced when diets containing 1056 mg of arginine were supplemented with 100 or 200 mg phytogenic additive per kg. Feed conversion ratio was improved when diets were supplemented with 100 mg of phytogenic additive or with 1056 mg of arginine per kg of feed. Egg mass was increased when diets were supplemented with 1056 mg arginine per kg of feed. Arginine supplementation quadratically increased albumen percentage and reduced yolk percentage. Higher arginine and phytogenic additive levels reduced heterophyl:lymphocyte ratio and blood uric acid, total cholesterol, very-low density lipoprotein, and triglyceride levels. Dietary supplementation of 100 mg of phytogenic additive associated with high arginine levels increased nitric oxide production by peritoneal macrophages and 1056 mg of arginine increased antibodies titers against Newcastle disease virus. Blood and intestinal malonaldehyde levels were reduced when 200 mg of the phytogenic additive was added. Dietary supplementation of 968 mg of arginine or 100 mg of a phytogenic additive (40% Baccharis dracunculifolia, 20% Astragalus membranaceus, 20% cinnamon, and 20% grape seed extracts per kilogram of diet improves the feed conversion ratio and associated inclusion of 1144 mg of

  15. L-arginine prevents hypoxia-induced vasoconstriction in dual-perfused human placental cotyledons.

    Science.gov (United States)

    Bednov, Andrey; Espinoza, Jimmy; Betancourt, Ancizar; Vedernikov, Yuri; Belfort, Michael; Yallampalli, Chandrasekhar

    2015-11-01

    Chronic hypoxia in the uteroplacental unit is associated with increased resistance to blood flow in the fetal-placental circulation. These changes can lead to adverse cardiovascular events in adulthood. This study investigates whether L-arginine (substrate for nitric oxide synthase (NOS) or endothelin-A receptor antagonist BQ123 administration reverses hypoxia-induced changes in perfusion pressure in the fetal compartment in dual-perfused placental cotyledons. Human placental cotyledons (n = 15) from term deliveries (n = 15) were perfused with Krebs solution from maternal and fetal sides. Normal and reduced oxygen tension conditions were sequentially created in the perfused maternal compartment. Fetal perfusion pressure was continuously monitored. 1 mM L-arginine, D-arginine (an enantiomer of L-arginine and not a substrate for NOS), and BQ123 or normal saline were administered to the fetal compartment; L-arginine was also administered to the maternal compartment prior to maternal side hypoxia. Changes in perfusion pressure were compared between groups. Maternal hypoxia increased (19 ± 6%) perfusion pressure and this was blunted by L-arginine injection (3 ± 5%; p = 0.006) into the fetal compartment. L-arginine in the maternal compartment had no significant effect (22 ± 4% with L-arginine vs.14 ± 3% at control) on perfusion pressure. Similarly, D-arginine (23 ± 11% vs.19 ± 8% at control) or BQ123 (12 ± 3% vs.13 ± 3% at control) in the fetal compartment did not blunt the hypoxia-induced increase in perfusion pressure. Fetal vasoconstriction induced by maternal hypoxia is blunted by NO synthase substrate L-arginine, but not by D-arginine, in the fetal compartment, suggesting the involvement of NO synthesis in regulating the hypoxia-induced fetal vasoconstriction. Endothelin A receptor-related mechanisms does not appear to play a role in the maternal hypoxia-induced fetal vasoconstriction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Bioinformatic evaluation of L-arginine catabolic pathways in 24 cyanobacteria and transcriptional analysis of genes encoding enzymes of L-arginine catabolism in the cyanobacterium Synechocystis sp. PCC 6803

    OpenAIRE

    Schriek, Sarah; R?ckert, Christian; Staiger, Dorothee; Pistorius, Elfriede K; Michel, Klaus-Peter

    2007-01-01

    Abstract Background So far very limited knowledge exists on L-arginine catabolism in cyanobacteria, although six major L-arginine-degrading pathways have been described for prokaryotes. Thus, we have performed a bioinformatic analysis of possible L-arginine-degrading pathways in cyanobacteria. Further, we chose Synechocystis sp. PCC 6803 for a more detailed bioinformatic analysis and for validation of the bioinformatic predictions on L-arginine catabolism with a transcript analysis. Results W...

  17. Homoarginine Levels are Regulated by L-Arginine:Glycine Amidinotransferase and Affect Stroke Outcome: Results from Human and Murine Studies

    NARCIS (Netherlands)

    Choe, C.-U.; Atzler, D.; Wild, P.S.; Carter, A.M.; B\\"oger, R.H.; Ojeda, F.; Simova, O.; Stockebrand, M.; Lackner, K.; Nabuurs, C.; Marescau, B.; Streichert, T.; M\\"uller, C.; L\\"uneburg, N.; Deyn, P.P. de; Benndorf, R.A.; Baldus, S.; Gerloff, C.; Blankenberg, S.; Heerschap, A.; Grant, P.J.; Magnus, T.; Zeller, T.; Isbrandt, D.; Schwedhelm, E.

    2013-01-01

    Endogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. Our studies of human cohorts and a confirmatory murine model associated the arginine homologue homoarginine and its metabolism in stroke pathology and

  18. Interactions between L-arginine/L-arginine derivatives and lysozyme and implications to their inhibition effects on protein aggregation.

    Science.gov (United States)

    Gao, Ming-Tao; Dong, Xiao-Yan; Sun, Yan

    2013-01-01

    L-arginine (Arg), L-homoarginine (HArg), L-arginine ethylester (ArgEE), and L-arginine methylester (ArgME) were found effective in inhibiting protein aggregation, but the molecular mechanisms are not clear. Herein, stopped-flow fluorescence spectroscopy, isothermal titration calorimetry, and mass spectroscopy were used to investigate the folding kinetics of lysozyme and the interactions of the additives with lysozyme. It was found that the interactions of ArgME and ArgEE with lysozyme were similar to that of guanidine hydrochloride and were much stronger than those of Arg and HArg. The binding forces were all mainly hydrogen bonding and cation-π interaction from the guanidinium group, but their differences in molecular states led to the significantly different binding strengths. The additives formed molecular clusters in an increasing order of ArgEE, ArgME, HArg, and Arg. Arg and HArg mainly formed annular clusters with head-to-tail bonding, while ArgME and ArgEE formed linear clusters with guanidinium groups stacking. The interactions between the additives and lysozyme were positively related to the monomer contents. That is, the monomers were the primary species that participated in the direct interactions due to their intact guanidinium groups and small sizes, while the clusters performed as barriers to crowd out the protein-protein interactions for aggregation. Thus, it is concluded that the effects of Arg and its derivatives on protein aggregation stemmed from the direct interactions by the monomers and the crowding effects by the clusters. Interplay of the two effects led to the differences in their inhibition effects on protein aggregation. © 2013 American Institute of Chemical Engineers.

  19. Enteral L-Arginine and Glutamine Supplementation for Prevention of NEC in Preterm Neonates

    Directory of Open Access Journals (Sweden)

    M. S. El-Shimi

    2015-01-01

    Full Text Available Objective. Evaluating the efficacy and safety of arginine and glutamine supplementation in decreasing the incidence of NEC among preterm neonates. Methods. Prospective case-control study done on 75 preterm neonates ≤34 weeks, divided equally into L-arginine group receiving enteral L-arginine, glutamine group receiving enteral glutamine, and control group. Serum L-arginine and glutamine levels were measured at time of enrollment (sample 1, after 14 days of enrollment (sample 2, and at time of diagnosis of NEC (sample 3. Results. The incidence of NEC was 9.3%. There was no difference in the frequency of NEC between L-arginine and control groups (P>0.05. NEC was not detected in glutamine group; L-arginine concentrations were significantly lower in arginine group than control group in both samples while glutamine concentrations were comparable in glutamine and control groups in both samples. No significant difference was found between groups as regards number of septic episodes, duration to reach full oral intake, or duration of hospital stay. Conclusion. Enteral L-arginine supplementation did not seem to reduce the incidence of NEC. Enteral glutamine may have a preventive role against NEC if supplied early to preterm neonates. However, larger studies are needed to confirm these findings. This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01263041.

  20. Arginine supplementation in four patients with X-linked creatine transporter defect

    NARCIS (Netherlands)

    Fons, C.; Sempere, A.; Arias, A.; Lopez-Sala, A.; Poo, P.; Pineda, M.; Mas, A.; Vilaseca, M.A.; Salomons, G.S.; Ribes, A.; Artuch, R.; Campistol, J.

    2008-01-01

    Background: Treatment with oral creatine monohydrate has not shown efficacy in patients with creatine transporter deficiency (CRTR-D). Another therapeutic option proposed is L-arginine, the substrate for the enzyme L-arginine:glycine amidinotransferase (AGAT). We evaluate clinical characteristics

  1. Abnormal Mitochondrial L-Arginine Transport Contributes to the Pathogenesis of Heart Failure and Rexoygenation Injury

    Science.gov (United States)

    Byrne, Melissa; Joshi, Mandar; Horlock, Duncan; Lam, Nicholas T.; Gregorevic, Paul; McGee, Sean L.; Kaye, David M.

    2014-01-01

    Background Impaired mitochondrial function is fundamental feature of heart failure (HF) and myocardial ischemia. In addition to the effects of heightened oxidative stress, altered nitric oxide (NO) metabolism, generated by a mitochondrial NO synthase, has also been proposed to impact upon mitochondrial function. However, the mechanism responsible for arginine transport into mitochondria and the effect of HF on such a process is unknown. We therefore aimed to characterize mitochondrial L-arginine transport and to investigate the hypothesis that impaired mitochondrial L-arginine transport plays a key role in the pathogenesis of heart failure and myocardial injury. Methods and Results In mitochondria isolated from failing hearts (sheep rapid pacing model and mouse Mst1 transgenic model) we demonstrated a marked reduction in L-arginine uptake (pL-arginine transporter, CAT-1 (pL-arginine transport in modulating cardiac stress responses was examined in cardiomyocytes with mitochondrial specific overexpression of CAT-1 (mtCAT1) exposed to hypoxia-reoxygenation stress. mtCAT1 cardiomyocytes had significantly improved mitochondrial membrane potential, respiration and ATP turnover together with significantly decreased reactive oxygen species production and cell death following mitochondrial stress. Conclusion These data provide new insights into the role of L-arginine transport in mitochondrial biology and cardiovascular disease. Augmentation of mitochondrial L-arginine availability may be a novel therapeutic strategy for myocardial disorders involving mitochondrial stress such as heart failure and reperfusion injury. PMID:25111602

  2. The do's and don'ts of arginine supplementation | Chetty | South ...

    African Journals Online (AJOL)

    In the last three decades the nutritional and pharmacologic effects of arginine have been the subject of intense investigation. Taking into consideration the many benefits that have been demonstrated from arginine supplementation, the question remains: “Can we afford not to supplement with this immuno-nutrient”.

  3. The ArcD1 and ArcD2 arginine/ornithine exchangers encoded in the arginine deiminase (ADI) pathway gene cluster of Lactococcus lactis

    NARCIS (Netherlands)

    Noens, Elke E E; Kaczmarek, Michał B; Żygo, Monika; Lolkema, Juke S

    2015-01-01

    The arginine deiminase pathway (ADI) gene cluster in Lactococcus lactis contains two copies of a gene encoding an L-arginine/L-ornithine exchanger, the arcD1 and arcD2 genes. The physiological function of ArcD1 and ArcD2 was studied by deleting the two genes. Deletion of arcD1 resulted in loss of

  4. Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation.

    Science.gov (United States)

    Lott, Kaylen; Li, Jun; Fisk, John C; Wang, Hao; Aletta, John M; Qu, Jun; Read, Laurie K

    2013-10-08

    Arginine methylation is a common posttranslational modification with reported functions in transcription, RNA processing and translation, and DNA repair. Trypanosomes encode five protein arginine methyltransferases, suggesting that arginine methylation exerts widespread impacts on the biology of these organisms. Here, we performed a global proteomic analysis of Trypanosoma brucei to identify arginine methylated proteins and their sites of modification. Using an approach entailing two-dimensional chromatographic separation and alternating electron transfer dissociation and collision induced dissociation, we identified 1332 methylarginines in 676 proteins. The resulting data set represents the largest compilation of arginine methylated proteins in any organism to date. Functional classification revealed numerous arginine methylated proteins involved in flagellar function, RNA metabolism, DNA replication and repair, and intracellular protein trafficking. Thus, arginine methylation has the potential to impact aspects of T. brucei gene expression, cell biology, and pathogenesis. Interestingly, pathways with known methylated proteins in higher eukaryotes were identified in this study, but often different components of the pathway were methylated in trypanosomes. Methylarginines were often identified in glycine rich contexts, although exceptions to this rule were detected. Collectively, these data inform on a multitude of aspects of trypanosome biology and serve as a guide for the identification of homologous arginine methylated proteins in higher eukaryotes. T. brucei is a protozoan parasite that causes lethal African sleeping sickness in humans and nagana in livestock, thereby imposing a significant medical and economic burden on sub-Saharan Africa. The parasite encounters very different environments as it cycles between mammalian and insect hosts, and must exert cellular responses to these varying milieus. One mechanism by which all cells respond to changing

  5. Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats.

    Science.gov (United States)

    Moretto, Johnny; Guglielmetti, Anne-Sophie; Tournier-Nappey, Maude; Martin, Hélène; Prigent-Tessier, Anne; Marie, Christine; Demougeot, Céline

    2017-04-01

    While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22-24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in

  6. PRmePRed: A protein arginine methylation prediction tool.

    Directory of Open Access Journals (Sweden)

    Pawan Kumar

    Full Text Available Protein methylation is an important Post-Translational Modification (PTMs of proteins. Arginine methylation carries out and regulates several important biological functions, including gene regulation and signal transduction. Experimental identification of arginine methylation site is a daunting task as it is costly as well as time and labour intensive. Hence reliable prediction tools play an important task in rapid screening and identification of possible methylation sites in proteomes. Our preliminary assessment using the available prediction methods on collected data yielded unimpressive results. This motivated us to perform a comprehensive data analysis and appraisal of features relevant in the context of biological significance, that led to the development of a prediction tool PRmePRed with better performance. The PRmePRed perform reasonably well with an accuracy of 84.10%, 82.38% sensitivity, 83.77% specificity, and Matthew's correlation coefficient of 66.20% in 10-fold cross-validation. PRmePRed is freely available at http://bioinfo.icgeb.res.in/PRmePRed/.

  7. Agmatine: multifunctional arginine metabolite and magic bullet in clinical neuroscience?

    Science.gov (United States)

    Laube, Gregor; Bernstein, Hans-Gert

    2017-07-26

    Agmatine, the decarboxylation product of arginine, was largely neglected as an important player in mammalian metabolism until the mid-1990s, when it was re-discovered as an endogenous ligand of imidazoline and α 2 -adrenergic receptors. Since then, a wide variety of agmatine-mediated effects have been observed, and consequently agmatine has moved from a wallflower existence into the limelight of clinical neuroscience research. Despite this quantum jump in scientific interest, the understanding of the anabolism and catabolism of this amine is still vague. The purification and biochemical characterization of natural mammalian arginine decarboxylase and agmatinase still are open issues. Nevertheless, the agmatinergic system is currently one of the most promising candidates in order to pharmacologically interfere with some major diseases of the central nervous system, which are summarized in the present review. Particularly with respect to major depression, agmatine, its derivatives, and metabolizing enzymes show great promise for the development of an improved treatment of this common disease. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  8. Arginine phosphorylation marks proteins for degradation by a Clp protease.

    Science.gov (United States)

    Trentini, Débora Broch; Suskiewicz, Marcin Józef; Heuck, Alexander; Kurzbauer, Robert; Deszcz, Luiza; Mechtler, Karl; Clausen, Tim

    2016-11-03

    Protein turnover is a tightly controlled process that is crucial for the removal of aberrant polypeptides and for cellular signalling. Whereas ubiquitin marks eukaryotic proteins for proteasomal degradation, a general tagging system for the equivalent bacterial Clp proteases is not known. Here we describe the targeting mechanism of the ClpC-ClpP proteolytic complex from Bacillus subtilis. Quantitative affinity proteomics using a ClpP-trapping mutant show that proteins phosphorylated on arginine residues are selectively targeted to ClpC-ClpP. In vitro reconstitution experiments demonstrate that arginine phosphorylation by the McsB kinase is required and sufficient for the degradation of substrate proteins. The docking site for phosphoarginine is located in the amino-terminal domain of the ClpC ATPase, as resolved at high resolution in a co-crystal structure. Together, our data demonstrate that phosphoarginine functions as a bona fide degradation tag for the ClpC-ClpP protease. This system, which is widely distributed across Gram-positive bacteria, is functionally analogous to the eukaryotic ubiquitin-proteasome system.

  9. The Role of Protein Arginine Methyltransferases in Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Ji Hye Kim

    2016-01-01

    Full Text Available Protein arginine methyltransferases (PRMTs mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV. Although most PRMTs do not require posttranslational modification (PTM to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6 in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.

  10. The second case of a young man with L-arginine-induced acute pancreatitis.

    Science.gov (United States)

    Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

    2018-04-21

    Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

  11. Arginine does not exacerbate markers of inflammation in cocultures of human enterocytes and leukocytes

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Negrier, I.; Neveux, N.

    2007-01-01

    the catabolism of serine, asparagine, and lysine, and reduced glutamine catabolism. Addition of arginine increased ornithine formation and moderately reduced transepithelial transport of methionine and other amino acids. Hence, arginine supplementation does not interfere with inflammation-associated cross......Enteral arginine supplementation in the critically ill has become a matter of controversy. In this study, we investigated effects of the addition of 0.4 and 1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte layer integrity, and amino acid transport. In this model...... with arginine did not affect epithelial integrity, production of any of the cytokines investigated, or the amount of nitric oxide. The amino acid used primarily by nonstimulated intestinal epithelial cells cocultured with leukocytes was glutamine. Activation of IEC with bacteria significantly enhanced...

  12. Potentiality of application of the conductometric L-arginine biosensors for the real sample analysis

    Directory of Open Access Journals (Sweden)

    Jaffrezic-Renault N.

    2012-12-01

    Full Text Available Aim. To determine an influence of serum components on the L-arginine biosensor sensitivity and to formulate practical recommendations for its reliable analysis. Methods. The L-arginine biosensor comprised arginase and urease co-immobilized by cross-linking. Results. The biosensor specificity was investigated based on a series of representative studies (namely, through urea determination in the serum; inhibitory effect studies of mercury ions; high temperature treatment of sensors; studying the biosensor sensitivity to the serum treated by enzymes, and selectivity studies. It was found that the response of the biosensor to the serum injections was determined by high sensitivity of the L-arginine biosensor toward not only to L-arginine but also toward two other basic amino acids (L-lysine and L-histidine. Conclusions. A detailed procedure of optimization of the conductometric biosensor for L-arginine determination in blood serum has been proposed.

  13. Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine Metabolism in Rats

    Directory of Open Access Journals (Sweden)

    Musalmah Mazlan

    2017-01-01

    Full Text Available Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.

  14. Preharvest L-arginine treatment induced postharvest disease resistance to Botrysis cinerea in tomato fruits.

    Science.gov (United States)

    Zheng, Yang; Sheng, Jiping; Zhao, Ruirui; Zhang, Jian; Lv, Shengnan; Liu, Lingyi; Shen, Lin

    2011-06-22

    L-arginine is the precursor of nitric oxide (NO). In order to examine the influence of L-arginine on tomato fruit resistance, preharvest green mature tomato fruits (Solanum lycopersicum cv. No. 4 Zhongshu) were treated with 0.5, 1, and 5 mM L-arginine. The reduced lesion size (in diameter) on fruit caused by Botrytis cinerea, as well as activities of phenylalanine ammonia-lyase (PAL), Chitinase (CHI), β-1,3-glucanase (GLU), and polyphenoloxidase (PPO), was compared between L-arginine treated fruits and untreated fruits. We found that induced resistance increased and reached the highest level at 3-6 days after treatment. Endogenous NO concentrations were positively correlated with PAL, PPO, CHI, and GLU activities after treatment with Pearson coefficients of 0.71, 0.94, 0.97, and 0.87, respectively. These results indicate that arginine induces disease resistance via its effects on NO biosynthesis and defensive enzyme activity.

  15. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

    DEFF Research Database (Denmark)

    Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas

    2016-01-01

    The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic...... kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified...... as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human...

  16. Nucleation studies of ZTC doped with L-arginine in supersaturated aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Balu, T. [Department of Physics, Aditanar College of Arts and Science, Tiruchendur 628 216 (India); Rajasekaran, T.R., E-mail: trrajasekaran@yahoo.co [Department of Physics, Manonmaniam Sundaranar University, Tirunelveli 627 012 (India); Murugakoothan, P. [Post Graduate and Research Department of Physics, Pachaiyappa' s College, Chennai 600 030 (India)

    2009-06-01

    The metastable zonewidth studies are carried out for various temperatures for supersaturated aqueous solutions of zinc thiourea chloride added with 1 mole % of L-arginine. The metastable zonewidth is increased with the addition of L-arginine. The induction period is experimentally determined and various critical nucleation parameters such as radius of critical nucleus, number of molecules in the critical nucleus, critical free energy of nucleus and interfacial tension are also calculated based on the classical theory for homogeneous crystal nucleation. The induction period is increased with the increase of L-arginine addition. The critical nucleation parameters vary with increase in doping concentration. It is also observed that the nucleation rate increases with the increase of supersaturation. The second harmonic generation (SHG) efficiency measurements are carried out with different doping concentration of L-arginine reveal that nonlinear optical (NLO) property is enhanced by L-arginine dopant.

  17. The arginine methyltransferase Rmt2 is enriched in the nucleus and co-purifies with the nuclear porins Nup49, Nup57 and Nup100

    International Nuclear Information System (INIS)

    Olsson, Ida; Berrez, Jean-Marc; Leipus, Arunas; Ostlund, Cecilia; Mutvei, Ann

    2007-01-01

    Arginine methylation is a post-translational modification of proteins implicated in RNA processing, protein compartmentalization, signal transduction, transcriptional regulation and DNA repair. In a screen for proteins associated with the nuclear envelope in the yeast Saccharomyces cerevisiae, we have identified the arginine methyltransferase Rmt2, previously shown to methylate the ribosomal protein L12. By indirect immunofluorescence and subcellular fractionations we demonstrate here that Rmt2 has nuclear and cytoplasmic localizations. Biochemical analysis of a fraction enriched in nuclei reveals that nuclear Rmt2 is resistant to extractions with salt and detergent, indicating an association with structural components. This was supported by affinity purification experiments with TAP-tagged Rmt2. Rmt2 was found to co-purify with the nucleoporins Nup49, Nup57 and Nup100, revealing a novel link between arginine methyltransferases and the nuclear pore complex. In addition, a genome-wide transcription study of the rmt2Δ mutant shows significant downregulation of the transcription of MYO1, encoding the Type II myosin heavy chain required for cytokinesis and cell separation

  18. Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

    Directory of Open Access Journals (Sweden)

    David Sabater

    2014-01-01

    rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

  19. Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Sun Yuan

    2006-02-01

    Full Text Available Abstract Background Arginine biosynthesis in Escherichia coli is elevated in response to nutrient limitation, stress or arginine restriction. Though control of the pathway in response to arginine limitation is largely modulated by the ArgR repressor, other factors may be involved in increased stationary phase and stress expression. Results In this study, we report that expression of the argCBH operon is induced in stationary phase cultures and is reduced in strains possessing a mutation in rpoS, which encodes an alternative sigma factor. Using strains carrying defined argR, and rpoS mutations, we evaluated the relative contributions of these two regulators to the expression of argH using operon-lacZ fusions. While ArgR was the main factor responsible for modulating expression of argCBH, RpoS was also required for full expression of this biosynthetic operon at low arginine concentrations (below 60 μM L-arginine, a level at which growth of an arginine auxotroph was limited by arginine. When the argCBH operon was fully de-repressed (arginine limited, levels of expression were only one third of those observed in ΔargR mutants, indicating that the argCBH operon is partially repressed by ArgR even in the absence of arginine. In addition, argCBH expression was 30-fold higher in ΔargR mutants relative to levels found in wild type, fully-repressed strains, and this expression was independent of RpoS. Conclusion The results of this study indicate that both derepression and positive control by RpoS are required for full control of arginine biosynthesis in stationary phase cultures of E. coli.

  20. Dietary silicon and arginine affect mineral element composition of rat femur and vertebra.

    Science.gov (United States)

    Seaborn, C D; Nielsen, F H

    2002-12-01

    Both arginine and silicon affect collagen formation and bone mineralization. Thus, an experiment was designed to determine if dietary arginine would alter the effect of dietary silicon on bone mineralization and vice versa. Male weanling Sprague-Dawley rats were assigned to groups of 12 in a 2 x 2 factorially arranged experiment. Supplemented to a ground corn/casein basal diet containing 2.3 microg Si/g and adequate arginine were silicon as sodium metasilicate at 0 or 35 microg/g diet and arginine at 0 or 5 mg/g diet. The rats were fed ad libitum deionized water and their respective diets for 8 wk. Body weight, liver weight/body weight ratio, and plasma silicon were decreased, and plasma alkaline phosphatase activity was increased by silicon deprivation. Silicon deprivation also decreased femoral calcium, copper, potassium, and zinc concentrations, but increased the femoral manganese concentration. Arginine supplementation decreased femoral molybdenum concentration but increased the femoral manganese concentration. Vertebral concentrations of phosphorus, sodium, potassium, copper, manganese, and zinc were decreased by silicon deprivation. Arginine supplementation increased vertebral concentrations of sodium, potassium, manganese, zinc, and iron. The arginine effects were more marked in the silicon-deprived animals, especially in the vertebra. Germanium concentrations of the femur and vertebra were affected by an interaction between silicon and arginine; the concentrations were decreased by silicon deprivation in those animals not fed supplemental arginine. The change in germanium is consistent with a previous finding by us suggesting that this element may be physiologically important, especially as related to bone DNA concentrations. The femoral and vertebral mineral findings support the contention that silicon has a physiological role in bone formation and that arginine intake can affect that role.

  1. Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia

    Science.gov (United States)

    Wijnands, Karolina A. P.; Vink, Hans; Briedé, Jacob J.; van Faassen, Ernst E.; Lamers, Wouter H.; Buurman, Wim A.; Poeze, Martijn

    2012-01-01

    Background Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. Methodology/Principal Findings To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg•g bodyweight−1•h−1), combined with either L-Citrulline (6.25 mg•h-1), L-Arginine (6.25 mg•h−1), or L-Alanine (isonitrogenous control; 12.5 mg•h−1) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. Conclusion/Significance L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the

  2. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia.

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    Karolina A P Wijnands

    Full Text Available BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg • g bodyweight(-1 • h(-1, combined with either L-Citrulline (6.25 mg • h-1, L-Arginine (6.25 mg • h(-1, or L-Alanine (isonitrogenous control; 12.5 mg • h(-1 during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. CONCLUSION/SIGNIFICANCE: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability

  3. Dietary arginine silicate inositol complex inhibits periodontal tissue loss in rats with ligature-induced periodontitis.

    Science.gov (United States)

    Dundar, Serkan; Eltas, Abubekir; Hakki, Sema S; Malkoc, Sıddık; Uslu, M Ozay; Tuzcu, Mehmet; Komorowski, James; Ozercan, I Hanifi; Akdemir, Fatih; Sahin, Kazim

    2016-01-01

    The purpose of this study was to induce experimental periodontitis in rats previously fed diets containing arginine silicate inositol (ASI) complex and examine the biochemical, immunological, and radiological effects. Fifty two 8-week-old female Sprague Dawley rats were equally divided into four groups. The control group included those fed a standard rat diet with no operation performed during the experiment. The periodontitis, ASI I, and ASI II groups were subjected to experimental periodontitis induction for 11 days after being fed a standard rat diet alone, a diet containing 1.81 g/kg ASI complex, or a diet containing 3.62 g/kg ASI complex, respectively, for 8 weeks. Throughout the 11-day duration of periodontitis induction, all rats were fed standard feed. The rats were euthanized on the eleventh day, and their tissue and blood samples were collected. In the periodontitis group, elevated tissue destruction parameters and reduced tissue formation parameters were found, as compared to the ASI groups. Levels of enzymes, cytokines, and mediators associated with periodontal tissue destruction were lower in rats fed a diet containing ASI complex after experimental periodontitis. These results indicate that ASI complex could be an alternative agent for host modulation.

  4. Prevalence of the lmo0036-0043 gene cluster encoding arginine deiminase and agmatine deiminase systems in Listeria monocytogenes.

    Science.gov (United States)

    Chen, Jianshun; Chen, Fan; Cheng, Changyong; Fang, Weihuan

    2013-04-01

    Arginine deiminase and agmatine deiminase systems are involved in acid tolerance, and their encoding genes form the cluster lmo0036-0043 in Listeria monocytogenes. While lmo0042 and lmo0043 were conserved in all L. monocytogenes strains, the lmo0036-0041 region of this cluster was identified in all lineages I and II, and the majority of lineage IV (83.3%) strains, but absent in all lineage III and a small fraction of lineage IV (16.7%) strains, suggesting that the presence of the complete lmo0036-0043 cluster is dependent on lineages. lmo0036-0043-complete and -deficient lineage IV strains exhibit specific ascB-dapE profiles, which might represent two subpopulations with distinct genetic characteristics.

  5. Molecular characteristics of clinical methicillin-resistant Staphylococcus pseudintermedius harboring arginine catabolic mobile element (ACME) from dogs and cats.

    Science.gov (United States)

    Yang, Ching; Wan, Min-Tao; Lauderdale, Tsai-Ling; Yeh, Kuang-Sheng; Chen, Charles; Hsiao, Yun-Hsia; Chou, Chin-Cheng

    2017-06-01

    This study aimed to investigate the presence of arginine catabolic mobile element (ACME) and its associated molecular characteristics in methicillin-resistant Staphylococcus pseudintermedius (MRSP). Among the 72 S. pseudintermedius recovered from various infection sites of dogs and cats, 52 (72.2%) were MRSP. ACME-arcA was detected commonly (69.2%) in these MRSP isolates, and was more frequently detected in those from the skin than from other body sites (P=0.047). There was a wide genetic diversity among the ACME-arcA-positive MRSP isolates, which comprised three SCCmec types (II-III, III and V) and 15 dru types with two predominant clusters (9a and 11a). Most MRSP isolates were multidrug-resistant. Since S. pseudintermedius could serve as a reservoir of ACME, further research on this putative virulence factor is recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Dietary arginine silicate inositol complex inhibits periodontal tissue loss in rats with ligature-induced periodontitis

    Directory of Open Access Journals (Sweden)

    Dundar S

    2016-11-01

    Full Text Available Serkan Dundar,1 Abubekir Eltas,2 Sema S Hakki,3 Sıddık Malkoc,4 M Ozay Uslu,2 Mehmet Tuzcu,5 James Komorowski,6 I Hanifi Ozercan,7 Fatih Akdemir,8 Kazim Sahin9 1Department of Periodontology, Faculty of Dentistry, Firat University, Elazig, 2Department of Periodontology, Faculty of Dentistry, Inonu University, Malatya, 3Department of Periodontology, Faculty of Dentistry, Selcuk University, Konya, 4Department of Orthodontics, Faculty of Dentistry, Inonu University, Malatya, 5Department of Biology, Faculty of Science, Firat University, Elazig, Turkey; 6Research & Development, Nutrition 21 Inc., Purchase, NY, USA; 7Department of Pathology, Faculty of Medicine, 8Department of Animal Nutrition, Faculty of Fisheries, Inonu University, Malatya, 9Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey Abstract: The purpose of this study was to induce experimental periodontitis in rats previously fed diets containing arginine silicate inositol (ASI complex and examine the biochemical, immunological, and radiological effects. Fifty two 8-week-old female Sprague Dawley rats were equally divided into four groups. The control group included those fed a standard rat diet with no operation performed during the experiment. The periodontitis, ASI I, and ASI II groups were subjected to experimental periodontitis induction for 11 days after being fed a standard rat diet alone, a diet containing 1.81 g/kg ASI complex, or a diet containing 3.62 g/kg ASI complex, respectively, for 8 weeks. Throughout the 11-day duration of periodontitis induction, all rats were fed standard feed. The rats were euthanized on the eleventh day, and their tissue and blood samples were collected. In the periodontitis group, elevated tissue destruction parameters and reduced tissue formation parameters were found, as compared to the ASI groups. Levels of enzymes, cytokines, and mediators associated with periodontal tissue destruction were lower

  7. Depletion of arginine in yeast cells decreases the resistance to hydrostatic pressure

    Science.gov (United States)

    Nomura, Kazuki; Iwahashi, Hitoshi; Iguchi, Akinori; Shigematsu, Toru

    2015-07-01

    High hydrostatic pressure (HP) inhibits growth and inactivates microorganisms by destabilizing non-covalent molecular interactions. Arginine contributes to stress resistance because it has a guanidine side chain, which assists in the refolding of aggregated proteins. We attempted to analyze the contribution of arginine to high HP stress using a pressure-sensitive mutant strain of Saccharomyces cerevisiae and a metabolomics approach. Our results showed that the content of 136 out of 250 detected metabolites differed in the mutant and parent strains. Decreased metabolites were involved in the tricarboxylic acid cycle and arginine biosynthesis. The expression of genes contributing to arginine biosynthesis was significantly lower in the mutant strain than in the parent strain. When arginine was supplemented to the medium, the mutant strain showed more tolerance to pressure. These results suggest that yeast cells survived due to the contribution of arginine to high pressure resistance. This indicates that depletion of arginine caused by decreased activity of the biosynthesis pathway confers sensitivity to HP.

  8. L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi.

    Science.gov (United States)

    Carbajosa, Sofía; Rodríguez-Angulo, Héctor O; Gea, Susana; Chillón-Marinas, Carlos; Poveda, Cristina; Maza, María C; Colombet, Diana; Fresno, Manuel; Gironès, Núria

    2018-01-01

    Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs.

  9. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

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    Mechteld A. R. Vermeulen

    2016-01-01

    Full Text Available Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%. Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  10. L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Sofía Carbajosa

    2018-01-01

    Full Text Available Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS. We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs.

  11. L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi

    Science.gov (United States)

    Gea, Susana; Chillón-Marinas, Carlos; Poveda, Cristina; Maza, María C.; Colombet, Diana; Fresno, Manuel

    2018-01-01

    Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs. PMID:29337988

  12. Asymmetric dimethylarginine and L-arginine levels in neonatal sepsis and septic shock.

    Science.gov (United States)

    Aydemir, Ozge; Ozcan, Beyza; Yucel, Husniye; Bas, Ahmet Yagmur; Demirel, Nihal

    2015-05-01

    Nitric oxide (NO) formed by the enzyme NO synthase (NOS) from L-arginine, is an important mediator for pathogen elimination. Being a potent vasodilator NO is implicated in hypotension and decreased organ perfusion in sepsis. Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor. We investigated ADMA and L-arginine levels in neonatal sepsis and their relation to disease severity. A prospective controlled study was conducted including 31 neonates with sepsis and 20 controls. Serum ADMA and L-arginine levels were measured within 24 h of sepsis diagnosis. Clinical and laboratory data including clinical risk index for babies (CRIB) score, presence of septic shock, organ dysfunction and death were recorded. L-arginine and ADMA levels were higher in neonates with sepsis compared to controls (p = 0.029 and p = 0.001, respectively). Neonates with septic shock had higher ADMA levels compared to septic neonates without shock (p = 0.026) and controls (p L-arginine levels were higher in neonates with septic shock compared to septic neonates without shock (p = 0.012) and controls (p L-arginine and ADMA levels. ADMA levels were correlated with CRIB score (rho = 0.320, p = 0.025). L-arginine and ADMA levels are elevated in neonatal sepsis and even higher levels are observed in septic shock.

  13. Protein substrates of the arginine methyltransferase Hmt1 identified by proteome arrays.

    Science.gov (United States)

    Low, Jason K K; Im, Hogune; Erce, Melissa A; Hart-Smith, Gene; Snyder, Michael P; Wilkins, Marc R

    2016-02-01

    Arginine methylation on nonhistone proteins is associated with a number of cellular processes including RNA splicing, protein localization, and the formation of protein complexes. In this manuscript, Saccharomyces cerevisiae proteome arrays carrying 4228 proteins were used with an antimethylarginine antibody to first identify 88 putatively arginine-methylated proteins. By treating the arrays with recombinant arginine methyltransferase Hmt1, 42 proteins were found to be possible substrates of this enzyme. Analysis of the putative arginine-methylated proteins revealed that they were predominantly nuclear or nucleolar in localization, consistent with the localization of Hmt1. Many are involved in known methylarginine-associated functions, such as RNA processing and ribonucleoprotein complex biogenesis, yet others are of newer classes, namely RNA/DNA helicases and tRNA-associated proteins. Using ex vivo methylation and MS/MS, a set of 12 proteins (Brr1, Dia4, Hts1, Mpp10, Mrd1, Nug1, Prp43, Rpa43, Rrp43, Spp381, Utp4, and Npl3), including the RNA helicase Prp43 and tRNA ligases Dia4 and Hts1, were all validated as Hmt1 substrates. Interestingly, the majority of these also had human orthologs, or family members, that have been documented elsewhere to carry arginine methylation. These results confirm arginine methylation as a widespread modification and Hmt1 as the major arginine methyltransferase in the S. cerevisiae cell. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Microwave heating of arginine yields highly fluorescent nanoparticles

    International Nuclear Information System (INIS)

    Philippidis, Aggelos; Stefanakis, Dimitrios; Anglos, Demetrios; Ghanotakis, Demetrios

    2013-01-01

    Brightly fluorescent nanoparticles were produced via a single-step, single-precursor procedure based on microwave heating of an aqueous solution of the amino acid arginine. Key structural and optical properties of the resulting Arg nanoparticles, Arg-dots, are reported and discussed with emphasis on the pH dependence of their fluorescence emission. The surface of the Arg-dots was functionalised through coupling to folic acid, opening up ways for connecting fluorescent nanoparticles to cancer cells. The generality and versatility of the microwave heating procedure was further demonstrated by the synthesis of different types of carbon nanoparticles, such as CE-dots, that were produced by use of citric acid and ethanolamine as precursors and compared to the Arg-dots.

  15. Haloarchaeal Protein Translocation via the Twin Arginine Translocation Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Pohlschroder Mechthild

    2009-02-03

    Protein transport across hydrophobic membranes that partition cellular compartments is essential in all cells. The twin arginine translocation (Tat) pathway transports proteins across the prokaryotic cytoplasmic membranes. Distinct from the universally conserved Sec pathway, which secretes unfolded proteins, the Tat machinery is unique in that it secretes proteins in a folded conformation, making it an attractive pathway for the transport and secretion of heterologously expressed proteins that are Sec-incompatible. During the past 7 years, the DOE-supported project has focused on the characterization of the diversity of bacterial and archaeal Tat substrates as well as on the characterization of the Tat pathway of a model archaeon, Haloferax volcanii, a member of the haloarchaea. We have demonstrated that H. volcanii uses this pathway to transport most of its secretome.

  16. Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles

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    Walter Wilczynski

    2017-08-01

    Full Text Available Arginine vasotocin (AVT is the non-mammalian homolog of arginine vasopressin (AVP and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens–amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT’s social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT’s many effects on behavior.

  17. Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles

    Science.gov (United States)

    Wilczynski, Walter; Quispe, Maricel; Muñoz, Matías I.; Penna, Mario

    2017-01-01

    Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens–amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT’s social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT’s many effects on behavior. PMID:28824546

  18. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    Science.gov (United States)

    Durmus, Ali Said; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Komorowski, James Richard; Ali, Shakir; Sahin, Kazim

    2017-05-01

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P < 0.05). The mean unhealed wound area was significantly smaller, and the mean percentage of total wound healing was significantly higher in ASI-treated wounds than in the control wounds. Hydroxyproline, collagen, and matrix metalloproteinases were measured in the granulated tissue and found to be affected. Inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), collagen, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  19. European Sea Bass (Dicentrarchus labrax) Immune Status and Disease Resistance Are Impaired by Arginine Dietary Supplementation.

    Science.gov (United States)

    Azeredo, Rita; Pérez-Sánchez, Jaume; Sitjà-Bobadilla, Ariadna; Fouz, Belén; Tort, Lluis; Aragão, Cláudia; Oliva-Teles, Aires; Costas, Benjamín

    2015-01-01

    Infectious diseases and fish feeds management are probably the major expenses in the aquaculture business. Hence, it is a priority to define sustainable strategies which simultaneously avoid therapeutic procedures and reinforce fish immunity. Currently, one preferred approach is the use of immunostimulants which can be supplemented to the fish diets. Arginine is a versatile amino acid with important mechanisms closely related to the immune response. Aiming at finding out how arginine affects the innate immune status or improve disease resistance of European seabass (Dicentrarchus labrax) against vibriosis, fish were fed two arginine-supplemented diets (1% and 2% arginine supplementation). A third diet meeting arginine requirement level for seabass served as control diet. Following 15 or 29 days of feeding, fish were sampled for blood, spleen and gut to assess cell-mediated immune parameters and immune-related gene expression. At the same time, fish from each dietary group were challenged against Vibrio anguillarum and survival was monitored. Cell-mediated immune parameters such as the extracellular superoxide and nitric oxide decreased in fish fed arginine-supplemented diets. Interleukins and immune-cell marker transcripts were down-regulated by the highest supplementation level. Disease resistance data were in accordance with a generally depressed immune status, with increased susceptibility to vibriosis in fish fed arginine supplemented diets. Altogether, these results suggest a general inhibitory effect of arginine on the immune defences and disease resistance of European seabass. Still, further research will certainly clarify arginine immunomodulation pathways thereby allowing the validation of its potential as a prophylactic strategy.

  20. Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice.

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    Vincent Marion

    Full Text Available Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass (fl and Villin-Cre mice. Unexpectedly, Ass (fl/fl /VilCre (tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice. Relative to control mice, citrulline production in the splanchnic region of Ass (fl/fl /VilCre (tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass (fl/fl /VilCre (tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2 and transport (Slc25a13, Slc25a15, and Slc3a2, whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver.

  1. Acute supplementation of L-arginine affects neither strength performance nor nitric oxide production.

    Science.gov (United States)

    Meirelles, Claudia M; Matsuura, Cristiane

    2018-03-01

    L-arginine is a semi-essential amino acid involved in nitric oxide production. As nitric oxide is an important vasodilator, L-arginine supplementation would increase blood perfusion and, subsequently, muscle performance during exercises. The aim of this study was to determine the acute effect of L-arginine supplementation on strength performance and nitric oxide levels in healthy trained individuals. In a double-blind, placebo-controlled, cross-over study, 12 men were randomly assigned to L-arginine or placebo supplementation. Subjects received 6 g of L-arginine or placebo 60 minutes before strength test (maximum number of repetitions, 3 sets at 70% of one repetition maximum on bench press and at 80% of one repetition maximum on knee extensions, 2 minutes of rest between sets and exercises). Blood samples were collected before supplementation and 6 min after exercise. Plasma nitrite levels did not significantly change after L-arginine or placebo supplementation and strength-training exercise (placebo, from 13.01±1.18 to 11.83±2.81 mM; L-arginine, from 10.95±4.09 to 11.99±2.5 mM). There was a significant reduction in the number of repetitions performed from set 1 to set 3 in each set of both bench press and knee extension, but no significant interactions were observed between placebo and L-arginine. These results do not support the use of L-arginine as an ergogenic aid for strength performance, at least in context of acute use immediately before resistance exercise performance.

  2. PRE-EXERCISE ARGININE SUPPLEMENTATION INCREASES TIME TO EXHAUSTION IN ELITE MALE WRESTLERS

    Directory of Open Access Journals (Sweden)

    H.U. Yavuz

    2014-08-01

    Full Text Available Dietary supplements containing arginine are among the most popular ergogenics intended to enhance strength, power and muscle recovery associated with both anaerobic and aerobic exercise. The aim of the present study was to evaluate the possible effect of pre-exercise acute intake of arginine on performance and exercise metabolism during incremental exhaustive exercise in elite male wrestlers. Nine volunteer elite male wrestlers (24.7±3.8 years participated in this study. The test-retest protocol was used on the same subjects. The study was conducted using a cross-over design. A single dose of arginine (1.5 g · 10 kg-1 body weight or placebo was given to the subjects after 12 hours fasting (during the night for both test and retest. Subjects were allowed to drink water but not allowed to eat anything between arginine or placebo ingestion and the exercise protocol. An incremental exercise protocol was applied and oxygen consumption was measured during the exercise. Heart rate and plasma lactate levels were measured during the exercise and recovery. Results showed that in the same working loads there was no significant difference for the mean lactate levels and no difference in maximum oxygen consumption (arginine 52.47±4.01 mL · kg-1 · min-1, placebo 52.07±5.21 mL · kg-1 · min-1 or in maximum heart rates (arginine 181.09±13.57 bpm, placebo 185.89±7.38 bpm between arginine and placebo trials. Time to exhaustion was longer with arginine supplementation (1386.8±69.8 s compared to placebo (1313±90.8 s (p<0.05. These results suggest that L-arginine supplementation can have beneficial effects on exercise performance in elite male wrestlers but cannot explain the metabolic pathways which are responsible from these effects.

  3. Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    Science.gov (United States)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P.; Woods, Stephen C.; Bräuner-Osborne, Hans; Seeley, Randy J.; D'Alessio, David A.

    2013-01-01

    Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1 and insulin and substantially improved glucose clearance. To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these improvements, l-arginine was given to Glp1r knockout mice and their wild-type littermates. In this experiment oral l-arginine significantly augmented insulin secretion and improved glucose clearance in WT mice, but not in Glp1r knockout littermates. Taken together these findings identify l-arginine as a GLP-1 secretagogue in vivo and demonstrate that improvement of glucose tolerance by oral l-arginine depends on GLP-1R-signaling. These findings raise the intriguing possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals. PMID:23959939

  4. Pre-exercise arginine supplementation increases time to exhaustion in elite male wrestlers.

    Science.gov (United States)

    Yavuz, H U; Turnagol, H; Demirel, A H

    2014-08-01

    Dietary supplements containing arginine are among the most popular ergogenics intended to enhance strength, power and muscle recovery associated with both anaerobic and aerobic exercise. The aim of the present study was to evaluate the possible effect of pre-exercise acute intake of arginine on performance and exercise metabolism during incremental exhaustive exercise in elite male wrestlers. Nine volunteer elite male wrestlers (24.7±3.8 years) participated in this study. The test-retest protocol was used on the same subjects. The study was conducted using a cross-over design. A single dose of arginine (1.5 g · 10 kg(-1) body weight) or placebo was given to the subjects after 12 hours fasting (during the night) for both test and retest. Subjects were allowed to drink water but not allowed to eat anything between arginine or placebo ingestion and the exercise protocol. An incremental exercise protocol was applied and oxygen consumption was measured during the exercise. Heart rate and plasma lactate levels were measured during the exercise and recovery. Results showed that in the same working loads there was no significant difference for the mean lactate levels and no difference in maximum oxygen consumption (arginine 52.47±4.01 mL · kg(-1) · min(-1), placebo 52.07±5.21 mL · kg(-1) · min(-1)) or in maximum heart rates (arginine 181.09±13.57 bpm, placebo 185.89±7.38 bpm) between arginine and placebo trials. Time to exhaustion was longer with arginine supplementation (1386.8±69.8 s) compared to placebo (1313±90.8 s) (p L-arginine supplementation can have beneficial effects on exercise performance in elite male wrestlers but cannot explain the metabolic pathways which are responsible from these effects.

  5. Dietary l-arginine inhibits intestinal Clostridium perfringens colonisation and attenuates intestinal mucosal injury in broiler chickens.

    Science.gov (United States)

    Zhang, Beibei; Lv, Zengpeng; Li, Huixian; Guo, Shuangshuang; Liu, Dan; Guo, Yuming

    2017-09-01

    We investigated the effects of dietary l-arginine level and feeding duration on the intestinal damage of broilers induced by Clostridium perfringens (CP) in vivo, and the antimicrobial effect of its metabolite nitric oxide (NO) in vitro. The in vivo experiment was designed as a factorial arrangement of three dietary treatments×two challenge statuses. Broilers were fed a basal diet (CON) or a high-arginine diet (ARG) containing 1·87 % l-arginine, or CON for the first 8 d and ARG from days 9 to 28 (CON/ARG). Birds were co-infected with or without Eimeria and CP (EM/CP). EM/CP challenge led to intestinal injury, as evidenced by lower plasma d-xylose concentration (Pl-arginine supplementation (Pl-arginine supplementation (Pl-arginine supplementation elevated (Pl-arginine supplementation could inhibit CP overgrowth and alleviate intestinal mucosal injury by modulating innate immune responses, enhancing barrier function and producing NO.

  6. l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats

    OpenAIRE

    Lee, Chee-Wan; Li, Dan; Channon, Keith M.; Paterson, David J.

    2009-01-01

    Spontaneously hypertensive rats (SHR) are known to have cardiac noradrenergic hyperactivity due to an impaired nitric oxide (NO)?cGMP pathway. We hypothesized that dietary l-arginine supplementation may correct this autonomic phenotype. Male SHR and Wistar Kyoto rats (WKY) aged 16?18?weeks were given l-arginine (10?g/L in drinking water) for 1?week. Separate control groups received no supplementation. The SHR control had a significantly lower plasma l-arginine than WKY control, but this was i...

  7. L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi

    OpenAIRE

    Carbajosa, Sofía; Rodríguez-Angulo, Héctor O.; Gea, Susana; Chillón-Marinas, Carlos; Poveda, Cristina; Maza, María C.; Colombet, Diana; Fresno, Manuel; Gironès, Núria

    2018-01-01

    Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced i...

  8. Dietary l-arginine supplementation improves semen quality and libido of boars under high ambient temperature.

    Science.gov (United States)

    Chen, J Q; Li, Y S; Li, Z J; Lu, H X; Zhu, P Q; Li, C M

    2017-12-04

    l-Arginine is a nutritionally essential amino acid for spermatogenesis and plays versatile roles in animal health and can be utilized as a potential agent to improve reproductive performance of boars under high ambient temperature. The present study aimed to determine whether dietary l-arginine could alleviate heat stress-induced infertility in boars. In all, 20 boars (PIC 1040; 248.59±3.84 kg BW and 407.65±6.40 days of age) were selected and randomly assigned to four groups (group 0.0%, basal diet; group 0.6%, 0.8% or 1.0%, basal diet added with 0.6%, 0.8% or 1.0% l-arginine (wt:wt), respectively.) The four diets were made isonitrogenous by addition of appropriate amounts of l-alanine. Boars were pre-fed the corresponding experimental diet for 42 days. Then, the semen characteristics and libido were accessed for 6 weeks during the hot summer period (25.5° to 33.0°C). Results show that dietary l-arginine remarkably improved sperm motility, normality, total sperm number and effective total sperm number. Also, dietary l-arginine improved semen antioxidant capacity, such as decrease of malondialdehyde and 8-Hydroxy-2'-deoxyguanosine content in sperm (Pl-arginine-supplemented group which also accompany with higher ATP content than the 0.0% group. The boars fed 0.8% l-arginine show increased levels of estradiol-17β and testosterone and exhibit improved libido performance than boars in the 0.0% group. Adding dietary l-arginine linearly increased (P=0.002) nitric oxide content (as l-arginine increased). The scrotal surface temperature in the 0.6%, 0.8% and 1.0% group were decreased by 0.9°C, 0.9°C and 0.4°C, respectively, compared with the 0.0% group. l-Arginine levels caused linear effect on semen quality and antioxidant capacity, also caused quadratic effect on libido performance. During the hot summer months, the predicted optimal l-arginine levels for best semen quality and antioxidant capacity was 0.8% to 1.0% and for best libido performance was 0.8%. It can

  9. Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice

    DEFF Research Database (Denmark)

    Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

    2014-01-01

    AIM: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. METHODS...... in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively) in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing...

  10. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    OpenAIRE

    Kuender D. Yang; Kuender D. Yang; Kuender D. Yang; Te-Yao Hsu; Hong-Ren Yu; Ching-Chang Tsai; Ling-Sai Chang; Hsin-Chun Huang; Hsin-Hsin Cheng; Jiu-Yao Wang; Jiu-Yao Wang; Jiunn-Ming Sheen; Ho-Chang Kuo; Kai-Sheng Hsieh; Ying-Hsien Huang

    2017-01-01

    A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhance...

  11. Mannitol/l-Arginine-Based Formulation Systems for Freeze Drying of Protein Pharmaceuticals: Effect of the l-Arginine Counter Ion and Formulation Composition on the Formulation Properties and the Physical State of Mannitol.

    Science.gov (United States)

    Stärtzel, Peter; Gieseler, Henning; Gieseler, Margit; Abdul-Fattah, Ahmad M; Adler, Michael; Mahler, Hanns-Christian; Goldbach, Pierre

    2016-10-01

    Previous studies have shown that protein storage stability in freeze-dried l-arginine-based systems improved in the presence of chloride ions. However, chloride ions reduced the glass transition temperature of the freeze concentrate (Tg') and made freeze drying more challenging. In this study, l-arginine was freeze dried with mannitol to obtain partially crystalline solids that can be freeze dried in a fast process and result in elegant cakes. We characterized the effect of different l-arginine counter ions on physicochemical properties of mannitol compared with mannitol/sucrose systems. Thermal properties of formulations with different compositions were correlated to thermal history during freeze drying and to physicochemical properties (cake appearance, residual moisture, reconstitution time, crystallinity). Partially crystalline solids were obtained even at the highest l-arginine level (mannitol:l-arginine of 2:1) used in this study. All l-arginine-containing formulations yielded elegant cakes. Only cakes containing l-arginine chloride and succinate showed a surface "crust" formed by phase separation. X-ray powder diffraction showed that inhibition of mannitol crystallization was stronger for l-arginine compared with sucrose and varied with the type of l-arginine counter ion. The counter ion affected mannitol polymorphism and higher levels of mannitol hemi-hydrate were obtained at high levels of l-arginine chloride. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Corticotropin-releasing hormone and arginine vasopressin in depression focus on the human postmortem hypothalamus

    NARCIS (Netherlands)

    Bao, Ai-Min; Swaab, Dick F.

    2010-01-01

    The neuropeptides corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are crucially involved in the pathogenesis of depression. The close correlation between the etiology of depression and dysregulation of the stress responses is based upon a hyperactivity of the

  13. LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis.

    Science.gov (United States)

    Liu, Bin; Du, Hongwei; Rutkowski, Rachael; Gartner, Anton; Wang, Xiaochen

    2012-07-20

    Defective catabolite export from lysosomes results in lysosomal storage diseases in humans. Mutations in the cystine transporter gene CTNS cause cystinosis, but other lysosomal amino acid transporters are poorly characterized at the molecular level. Here, we identified the Caenorhabditis elegans lysosomal lysine/arginine transporter LAAT-1. Loss of laat-1 caused accumulation of lysine and arginine in enlarged, degradation-defective lysosomes. In mutants of ctns-1 (C. elegans homolog of CTNS), LAAT-1 was required to reduce lysosomal cystine levels and suppress lysosome enlargement by cysteamine, a drug that alleviates cystinosis by converting cystine to a lysine analog. LAAT-1 also maintained availability of cytosolic lysine/arginine during embryogenesis. Thus, LAAT-1 is the lysosomal lysine/arginine transporter, which suggests a molecular explanation for how cysteamine alleviates a lysosomal storage disease.

  14. Utilization of arginine as an energy source for the growth of Streptococcus faecalis.

    Science.gov (United States)

    Deibel, R H

    1964-05-01

    Deibel, R. H. (American Meat Institute Foundation, Chicago, Ill.). Utilization of arginine as an energy source for the growth of Streptococcus faecalis. J. Bacteriol. 87:988-992. 1964.-Although both Streptococcus faecalis and S. faecium (and its variety durans) hydrolyze arginine, the utilization of this amino acid as an energy source appears to have taxonomic utility, as only S. faecalis and its varieties can couple the resultant energy with growth processes. Utilization of arginine by S. faecalis in a semisynthetic, casein-hydrolysate medium requires small concentrations of a fermentable carbohydrate (0.05%), presumably for synthetic reactions. The arginine analogue, agmatine, is utilized as an energy source by S. faecalis but not by S. faecium, and only approxinately 50% of the latter strains hydrolyzed this compound. Other ureido- and guanido-containing compounds tested were neither utilized as an energy source nor deaminated.

  15. Evidence that the presence of arginine can lead to overestimation of glucagon levels measured by radioimmunoassay

    International Nuclear Information System (INIS)

    Lacey, R.J.; Morgan, N.G.; Scarpello, J.H.B.

    1992-01-01

    Accurate measurement of glucagon levels by radioimmunoassay (RIA) has proved more difficult than with certain other hormones and wide variations in the concentration of this hormone in plasma have been reported. During recent studies glucagon secretion from isolated rat pancreatic islets incubated in vitro was measured using L-arginine as stimulus. In view of the reported difficulties associated with measurement of glucagon by RIA, it was considered important to examine whether L-arginine might affect the accuracy of glucagon measurement. In the present work, it is reported that L-arginine can interfere with measurement of glucagon by RIA, leading to overestimation of glucagon levels. It is suggested that possible artifactual effects of the amino acid should be considered when arginine is employed as a stimulus for glucagon secretion. (author). 15 refs., 4 figs

  16. Performance and nitrogen balance of laying hens fed increasing levels of digestible lysine and arginine

    Directory of Open Access Journals (Sweden)

    Fabyola Barros de Carvalho

    2012-10-01

    Full Text Available The objective of this experiment was to evaluate the effect of two digestible lysine levels and four digestible arginine levels on laying hens from 24 to 48 weeks of age. Three hundred and twenty Lohmann LSL laying hens were allotted in a completely randomized design in a 2 × 4 factorial arrangement, with two levels of digestible lysine (700 and 900 mg/kg of diet and four digestible arginine levels (700, 800, 900 and 1000 mg/kg of diet. Results indicated requirement of 884 and 830 mg of digestible arginine/kg of diet, considering an average feed intake of 95 g/hen/day and an average hen weight of 1.5 kg, aiming at lesser feed intake and better nutritional balance of nitrogen, respectively. High digestible lysine levels in the diet require higher digestible arginine supplementation for a better performance of hens.

  17. Large-Scale Identification of the Arginine Methylome by Mass Spectrometry

    DEFF Research Database (Denmark)

    Sylvestersen, Kathrine B; Nielsen, Michael L

    2015-01-01

    , prefractionation using strong cation exchange, and identification using liquid chromatography coupled to tandem mass spectrometry. A strategy for relative quantification is described using stable isotope labeling by amino acids in cell culture (SILAC). Approaches for analysis of arginine methylation site occupancy......The attachment of one or more methylation groups to the side chain of arginine residues is a regulatory mechanism for cellular proteins. Recent advances in mass spectrometry-based characterization allow comprehensive identification of arginine methylation sites by peptide-level enrichment...... strategies. Described in this unit is a 4-day protocol for enrichment of arginine-methylated peptides and subsequent identification of thousands of distinct sites by mass spectrometry. Specifically, the protocol explains step-by-step sample preparation, enrichment using commercially available antibodies...

  18. Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

    International Nuclear Information System (INIS)

    Sunatkari, A. L.; Talwatkar, S. S.; Tamgadge, Y. S.; Muley, G. G.

    2016-01-01

    We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

  19. Tyrosine binding and promiscuity in the arginine repressor from the pathogenic bacterium Corynebacterium pseudotuberculosis.

    Science.gov (United States)

    Mariutti, Ricardo Barros; Ullah, Anwar; Araujo, Gabriela Campos; Murakami, Mario Tyago; Arni, Raghuvir Krishnaswamy

    2016-07-08

    The arginine repressor (ArgR) regulates arginine biosynthesis in a number of microorganisms and consists of two domains interlinked by a short peptide; the N-terminal domain is involved in DNA binding and the C-terminal domain binds arginine and forms a hexamer made-up of a dimer of trimers. The crystal structure of the C-terminal domain of ArgR from the pathogenic Corynebacterium pseudotuberculosis determined at 1.9 Å resolution contains a tightly bound tyrosine at the arginine-binding site indicating hitherto unobserved promiscuity. Structural analysis of the binding pocket displays clear molecular adaptations to accommodate tyrosine binding suggesting the possible existence of an alternative regulatory process in this pathogenic bacterium. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

    NARCIS (Netherlands)

    Vermeulen, Mechteld A. R.; Brinkmann, Saskia J. H.; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M.; Houdijk, Alexander P. J.; van Goudoever, Johannes B.; van Leeuwen, Paul A. M.

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of

  1. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia

    NARCIS (Netherlands)

    Wijnands, Karolina A. P.; Vink, Hans; Briedé, Jacob J.; van Faassen, Ernst E.; Lamers, Wouter H.; Buurman, Wim A.; Poeze, Martijn

    2012-01-01

    Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome

  2. Dietary L-arginine supplementation enhances placental growth and reproductive performance in sows.

    Science.gov (United States)

    Gao, Kaiguo; Jiang, Zongyong; Lin, Yingcai; Zheng, Chuntian; Zhou, Guilian; Chen, Fang; Yang, Lin; Wu, Guoyao

    2012-06-01

    Suboptimal embryonic/fetal survival and growth remains a significant problem in mammals. Using a swine model, we tested the hypothesis that dietary L-arginine supplementation during gestation may improve pregnancy outcomes through enhancing placental growth and modulating hormonal secretions. Gestating pigs (Yorkshire×Landrace, n=108) were assigned randomly into two groups based on parity and body weight, representing dietary supplementation with 1.0% L-arginine-HCl or 1.7% L-alanine (isonitrogenous control) between days 22 and 114 of gestation. Blood samples were obtained from the ear vein on days 22, 40, 70 and 90 of gestation. On days 40, 70 and 90 of gestation, concentrations of estradiol in plasma were higher (Psupplemented than in control sows. Moreover, arginine supplementation increased (Psupplementation increased (Psupplementation enhanced (Psupplementation during gestation. These results indicate that dietary arginine supplementation beneficially enhances placental growth and the reproductive performance of sows.

  3. Microcirculatory effects of L-arginine during acute anaerobic exercise in healthy men: A pilot study

    Directory of Open Access Journals (Sweden)

    Andrius Pranskunas

    2015-12-01

    Conclusion: Our findings show that supplementation with L-arginine may cause additional effects on the acute anaerobic exercise-induced transient increase in capillary density in the sublingual mucosa of untrained men.

  4. Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

    Energy Technology Data Exchange (ETDEWEB)

    Sunatkari, A. L., E-mail: ashok.sunatkari@rediffmail.com [Department of Physics, Siddhartha College of Arts, Science and Commerce, Fort, Mumbai-400001, India. Email: ashok.sunatkari@rediffmail.com (India); Talwatkar, S. S. [Department of Physics, N.G. Aacharya and D.K. Maratha College of Arts, Science and Commerce, Chembur, Mumbai-400071, India. Email: swarna-81@rediffmail.com (India); Tamgadge, Y. S. [Department of Physics, Mahatma Phule Arts, Commerce & S.R.C. Science College, Warud-444906, India. Email: ystamgadge@gmail.com (India); Muley, G. G., E-mail: gajananggm@yahoo.co.in [Department of Physics, Sant Gadge Baba Amravati University, Amravati-444602 India. Email: gajananggm@yahoo.co.in (India)

    2016-05-06

    We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

  5. Arginine methylation analysis of the splicing-associated SR protein SFRS9/SRP30C.

    Science.gov (United States)

    Bressan, Gustavo C; Moraes, Eduardo C; Manfiolli, Adriana O; Kuniyoshi, Tais M; Passos, Dario O; Gomes, Marcelo D; Kobarg, Jörg

    2009-01-01

    The human SFRS9/SRp30c belongs to the SR family of splicing regulators. Despite evidence that members of this protein family may be targeted by arginine methylation, this has yet to be experimentally addressed. In this study, we found that SFRS9 is a target for PRMT1-mediated arginine methylation in vitro, and that it is immunoprecipitated from HEK-293 lysates by antibodies that recognize both mono- and dimethylated arginines. We further observed that upon treatment with the methylation inhibitor Adox, the fluorescent EGFP-SFRS9 re-localizes to dot-like structures in the cell nucleus. In subsequent confocal analyses, we found that EGFP-SFRS9 localizes to nucleoli in Adox-treated cells. Our findings indicate the importance of arginine methylation for the subnuclear localization of SFRS9.

  6. Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

    Science.gov (United States)

    Flynn, K M; Kellihan, H B; Trepanier, L A

    2017-08-01

    To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. New Insights into the Methodology of L-Arginine-Induced Acute Pancreatitis

    Science.gov (United States)

    Kui, Balázs; Balla, Zsolt; Vasas, Béla; Végh, Eszter T.; Pallagi, Petra; Kormányos, Eszter S.; Venglovecz, Viktória; Iványi, Béla; Takács, Tamás; Hegyi, Péter; Rakonczay, Zoltán

    2015-01-01

    Animal models are ideal to study the pathomechanism and therapy of acute pancreatitis (AP). The use of L-arginine-induced AP model is nowadays becoming increasingly popular in mice. However, carefully looking through the literature, marked differences in disease severity could be observed. In fact, while setting up the L-arginine (2×4 g/kg i.p.)-induced AP model in BALB/c mice, we found a relatively low rate (around 15%) of pancreatic necrosis, whereas others have detected much higher rates (up to 55%). We suspected that this may be due to differences between mouse strains. We administered various concentrations (5–30%, pH = 7.4) and doses (2×4, 3×3, or 4×2.5 g/kg) of L-arginine-HCl in BALB/c, FVB/n and C57BL/6 mice. The potential gender-specific effect of L-arginine was investigated in C57BL/6 mice. The fate of mice in response to the i.p. injections of L arginine followed one of three courses. Some mice (1) developed severe AP or (2) remained AP-free by 72 h, whereas others (3) had to be euthanized (to avoid their death, which was caused by the high dose of L-arginine and not AP) within 12 h., In FVB/n and C57BL/6 mice, the pancreatic necrosis rate (about 50%) was significantly higher than that observed in BALB/c mice using 2×4 g/kg 10% L–arginine, but euthanasia was necessary in a large proportion of animals, The i.p. injection of lower L-arginine concentrations (e.g. 5–8%) in case of the 2×4 g/kg dose, or other L-arginine doses (3×3 or 4×2.5 g/kg, 10%) were better for inducing AP. We could not detect any significant differences between the AP severity of male and female mice. Taken together, when setting up the L-arginine-induced AP model, there are several important factors that are worth consideration such as the dose and concentration of the administered L arginine-HCl solution and also the strain of mice. PMID:25688985

  8. Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy.

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    Michelle Wehling-Henricks

    2010-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD.We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial

  9. The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice.

    Science.gov (United States)

    Zakaria, Zainul Amiruddin; Sulaiman, Mohd Rosian; Somchit, Muhammad Nazrul; Jais, Abdul Manan Mat; Ali, Daud Israf

    2005-08-03

    To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test. The ASH was prepared by soaking fresh haruan fillet in chloroform:methanol (CM) (2/1 (v/v)) for 72 h followed by evaporation of the upper layer supernatant to remove any solvent residues. The supernatant was then subjected to a freeze-drying process (48 h) followed by doses preparation. Subcutaneous (SC) administration of ASH alone (0.170, 0.426 and 1.704 mg/kg) exhibited a dose-dependent antinociception. On the other hand, 20 mg/kg (SC) of L-arginine and MB exhibited a significant nociception and antinociception, while D-arginine and L-NAME did not produce any effect at all. Pre-treatment with L-arginine was found to significantly reverse the three respective doses of ASH antinociception; pre-treatment with D-arginine did not produce any significant change in the ASH activity; pre-treatment with L-NAME only significantly increased the 0.170 and 0.426 mg/kg ASH antinociception; and pre-treatment with MB significantly enhanced the respective doses of ASH antinociception, respectively. Furthermore, co-treatment with L-NAME significantly enhanced the L-arginine reversal effect on 0.426 mg/kg ASH antinociception. In addition, MB significantly reversed the L-arginine nociception on 0.426 mg/kg ASH. These finding suggest ASH antinociception involves the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. The presence of NO was found to reverse ASH antinociceptive activity while blocking of cGMP system enhanced it.

  10. CcpA regulates arginine biosynthesis in Staphylococcus aureus through repression of proline catabolism.

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    Austin S Nuxoll

    Full Text Available Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, arcB1, argG and argH abolished the ability of S. aureus JE2 ccpA::tetL to grow in the absence of arginine, whereas an interruption in argJBCF, arcB2, or proC had no effect. Furthermore, nuclear magnetic resonance demonstrated that JE2 ccpA::ermB produced (13C(5 labeled arginine when grown with (13C(5 proline. Taken together, these data support the conclusion that S. aureus synthesizes arginine from proline during growth on secondary carbon sources. Furthermore, although highly conserved in all sequenced S. aureus genomes, the arginine anabolic pathway (ArgJBCDFGH is not functional under in vitro growth conditions. Finally, a mutation in argH attenuated virulence in a mouse kidney abscess model in comparison to wild type JE2 demonstrating the importance of arginine biosynthesis in vivo via the urea cycle. However, mutations in argB, argF, and putA did not attenuate virulence suggesting both the glutamate and proline pathways are active and they, or their pathway intermediates, can complement each other in vivo.

  11. LAAT-1 is the Lysosomal Lysine/Arginine Transporter that Maintains Amino Acid Homeostasis

    OpenAIRE

    Liu, Bin; Du, Hongwei; Rutkowski, Rachael; Gartner, Anton; Wang, Xiaochen

    2012-01-01

    Defective catabolite export from lysosomes results in lysosomal storage diseases in humans. Mutations in the cystine transporter gene CTNS cause cystinosis, but other lysosomal amino acid transporters are poorly characterized at the molecular level. Here we identified the C. elegans lysosomal lysine/arginine transporter, LAAT-1. Loss of laat-1 caused accumulation of lysine and arginine in enlarged, degradation-defective lysosomes. In mutants of ctns-1 (C. elegans homolog of CTNS), LAAT-1 was ...

  12. Insulin rapidly stimulates L-arginine transport in human aortic endothelial cells via Akt.

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    Kohlhaas, Christine F; Morrow, Valerie A; Jhakra, Neelam; Patil, Vrushali; Connell, John M C; Petrie, John R; Salt, Ian P

    2011-09-09

    Insulin stimulates endothelial NO synthesis, at least in part mediated by phosphorylation and activation of endothelial NO synthase at Ser1177 and Ser615 by Akt. We have previously demonstrated that insulin-stimulated NO synthesis is inhibited under high culture glucose conditions, without altering Ca(2+)-stimulated NO synthesis or insulin-stimulated phosphorylation of eNOS. This indicates that stimulation of endothelial NO synthase phosphorylation may be required, yet not sufficient, for insulin-stimulated nitric oxide synthesis. In the current study we investigated the role of supply of the eNOS substrate, L-arginine as a candidate parallel mechanism underlying insulin-stimulated NO synthesis in cultured human aortic endothelial cells. Insulin rapidly stimulated L-arginine transport, an effect abrogated by incubation with inhibitors of phosphatidylinositol-3'-kinase or infection with adenoviruses expressing a dominant negative mutant Akt. Furthermore, supplementation of endothelial cells with extracellular L-arginine enhanced insulin-stimulated NO synthesis, an effect reversed by co-incubation with the L-arginine transport inhibitor, L-lysine. Basal L-arginine transport was significantly increased under high glucose culture conditions, yet insulin-stimulated L-arginine transport remained unaltered. The increase in L-arginine transport elicited by high glucose was independent of the expression of the cationic amino acid transporters, hCAT1 and hCAT2 and not associated with any changes in the activity of ERK1/2, Akt or protein kinase C (PKC). We propose that rapid stimulation of L-arginine transport contributes to insulin-stimulated NO synthesis in human endothelial cells, yet attenuation of this is unlikely to underlie the inhibition of insulin-stimulated NO synthesis under high glucose conditions. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Insulin rapidly stimulates l-arginine transport in human aortic endothelial cells via Akt

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    Kohlhaas, Christine F.; Morrow, Valerie A.; Jhakra, Neelam; Patil, Vrushali; Connell, John M.C.; Petrie, John R.; Salt, Ian P.

    2011-01-01

    Insulin stimulates endothelial NO synthesis, at least in part mediated by phosphorylation and activation of endothelial NO synthase at Ser1177 and Ser615 by Akt. We have previously demonstrated that insulin-stimulated NO synthesis is inhibited under high culture glucose conditions, without altering Ca2+-stimulated NO synthesis or insulin-stimulated phosphorylation of eNOS. This indicates that stimulation of endothelial NO synthase phosphorylation may be required, yet not sufficient, for insulin-stimulated nitric oxide synthesis. In the current study we investigated the role of supply of the eNOS substrate, l-arginine as a candidate parallel mechanism underlying insulin-stimulated NO synthesis in cultured human aortic endothelial cells. Insulin rapidly stimulated l-arginine transport, an effect abrogated by incubation with inhibitors of phosphatidylinositol-3′-kinase or infection with adenoviruses expressing a dominant negative mutant Akt. Furthermore, supplementation of endothelial cells with extracellular l-arginine enhanced insulin-stimulated NO synthesis, an effect reversed by co-incubation with the l-arginine transport inhibitor, l-lysine. Basal l-arginine transport was significantly increased under high glucose culture conditions, yet insulin-stimulated l-arginine transport remained unaltered. The increase in l-arginine transport elicited by high glucose was independent of the expression of the cationic amino acid transporters, hCAT1 and hCAT2 and not associated with any changes in the activity of ERK1/2, Akt or protein kinase C (PKC). We propose that rapid stimulation of L-arginine transport contributes to insulin-stimulated NO synthesis in human endothelial cells, yet attenuation of this is unlikely to underlie the inhibition of insulin-stimulated NO synthesis under high glucose conditions. PMID:21871446

  14. Acute hypothalamic administration of L-arginine increases feed intake in rats

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    Carlos Ricardo Maneck Malfatti

    2015-02-01

    Full Text Available Objective: This study investigated the chronic (oral and acute (hypothalamic infusion effects of L-arginine supplementation on feed intake, body composition, and behavioral changes in rats. Methods: Twenty rats were divided into two groups treated orally for 60 days; one group received L-arginine (1 g/kg body weight and one group received saline (1 mL/NaCl 0.9%. Daily consumption of water and food were evaluated, and weight monitored. After the oral treatment, the rats underwent stereotactic biopsy and a group was injected with 2 µL of L-arginine (0.5 mM and another received an injection of saline (0.9% NaCl, in the hypothalamic route, through micro infusion. Immediately after micro infusion, the animal behavior was evaluated through tests in the open field. Food and water consumption were evaluated at 12 and 24 hours after the micro infusion. Daily water consumption and weight gain evolution were evaluated. At the end of treatments, rats were euthanized and blood was collected for glucose, glycerol, and cholesterol evaluation, and histological analysis of vital organs. Results: Oral supplementation with L-arginine increased water intake (11%, p<0.05 and promoted weight gain (3%, p<0.05. However, hypothalamic infusion promoted a significant increase in chow intake (30%, p<0.05 after 24 hours of L-arginine administration. Conclusion: Chronic oral treatment with L-arginine was not effective on appetite modulation; however, an effect was observed when L-arginine was administered directly into the hypothalamus, suggesting a central regulation on appetite through nNOS sensitization. Chronic use of L-arginine did not cause substantial changes in anthropometric, biochemical, behavioral, or histological variables.

  15. Influence of L-arginine supplementation on reproductive blood flow and embryo recovery rates in mares.

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    Kelley, Dale; LeBlanc, Michelle M; Warren, Lori K; Mortensen, Christopher J

    2014-03-15

    Supplementation with L-arginine can increase uterine arterial blood flow and vascular perfusion of the preovulatory follicle in mares. Increased vascular perfusion of the preovulatory follicle has been correlated with successful pregnancy in mares. The objective of this study was to determine if supplemental L-arginine would increase ovarian arterial blood flow, vascular perfusion of the preovulatory follicle, and embryo recovery rates in mares. Mares were blocked by age and breed and assigned at random within block to L-arginine supplementation or control groups. Mares were fed L-arginine beginning 17 days before and through the duration of the study. Transrectal Doppler ultrasonography was used to measure ovarian arterial blood flow and vascular perfusion of the preovulatory follicle daily when it reached 35 mm and subsequent CL on Days 2, 4, and 6. Mares, on achieving a follicle of 35 mm or more were bred via artificial insemination and an embryo collection was attempted 7 days after ovulation. Treatment did not affect interovulatory interval (arginine-treated, 18.1 ± 2.6 days; control, 20.7 ± 2.3 days) or embryo recovery rate (arginine-treated, 54%; control, 48%). Mares treated with l-arginine had a larger follicle for the 10 days preceding ovulation than control mares (30.4 ± 1.2 and 26.3 ± 1.3 mm, respectively; P l-arginine supplementation increased the size and tended to increase perfusion of the follicle 1, but had no effect on luteal perfusion or embryo recovery rates in mares. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Effect of L-arginine supplement on liver regeneration after partial hepatectomy in rats

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    Kurokawa Tsuyoshi

    2012-05-01

    Full Text Available Abstract Background Nitric oxide (NO has been reported to be a key mediator in hepatocyte proliferation during liver regeneration. NO is the oxidative metabolite of L-arginine, and is produced by a family of enzymes, collective termed nitric oxide synthase (NOS. Thus, administration of L-arginine might enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine, which plays an important role in catabolic states and is a crucial factor in various cellular and organ functions, is widely known to enhance liver regeneration experimentally. Thus, the present study was undertaken to evaluate the effects of an L-arginine supplement on liver regeneration, and to compared this with supplementation with L-glutamine and L-alanine (the latter as a negative control, using a rat partial hepatectomy model. Methods Before and after a 70% hepatectomy, rats received one of three amino acid solutions (L-arginine, L-glutamine, or L-alanine. The effects on liver regeneration of the administered solutions were examined by assessment of restituted liver mass, staining for proliferating cell nuclear antigen (PCNA, and total RNA and DNA content 24 and 72 hours after the operation. Results At 72 hours after the hepatectomy, the restituted liver mass, the PCNA labeling index and the DNA quantity were all significantly higher in the L-arginine and L-glutamine groups than in the control. There were no significant differences in those parameters between the L-arginine and L-glutamine groups, nor were any significant differences found between the L-alanine group and the control. Conclusion Oral supplements of L-arginine and L-glutamine enhanced liver regeneration after hepatectomy in rats, suggesting that an oral arginine supplement can clinically improve recovery after a major liver resection.

  17. Cleansing effect of acidic L-arginine on human oral biofilm.

    Science.gov (United States)

    Tada, Ayano; Nakayama-Imaohji, Haruyuki; Yamasaki, Hisashi; Hasibul, Khaleque; Yoneda, Saori; Uchida, Keiko; Nariya, Hirofumi; Suzuki, Motoo; Miyake, Minoru; Kuwahara, Tomomi

    2016-03-22

    Dental plaque formed on tooth surfaces is a complex ecosystem composed of diverse oral bacteria and salivary components. Accumulation of dental plaque is a risk factor for dental caries and periodontal diseases. L-arginine has been reported to decrease the risk for dental caries by elevating plaque pH through the activity of arginine deiminase in oral bacteria. Here we evaluated the potential of L-arginine to remove established oral biofilms. Biofilms were formed using human saliva mixed with Brain Heart Infusion broth supplemented with 1 % sucrose in multi-well plates or on plastic discs. After washing the biofilms with saline, citrate (10 mM, pH3.5), or L-arginine (0.5 M, pH3.5), the retained biofilms were analyzed by crystal violet staining, scanning electron microscopy, and Illumina-based 16S rDNA sequencing. Washing with acidic L-arginine detached oral biofilms more efficiently than saline and significantly reduced biofilm mass retained in multi-well plates or on plastic discs. Illumina-based microbiota analysis showed that citrate (pH3.5) preferentially washed out Streptococcus from mature oral biofilm, whereas acidic L-arginine prepared with 10 mM citrate buffer (pH3.5) non-specifically removed microbial components of the oral biofilm. Acidic L-arginine prepared with citrate buffer (pH3.5) effectively destabilized and removed mature oral biofilms. The acidic L-arginine solution described here could be used as an additive that enhances the efficacy of mouth rinses used in oral hygiene.

  18. Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.

    OpenAIRE

    Granger, D L; Hibbs, J B; Perfect, J R; Durack, D T

    1988-01-01

    The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10% dialyzed fetal bovine serum. Fungistasis was measured using electronic particle counting after lysis of macrophages with detergent. Macrophage fungistasis failed in medium lacking only L-arginine. Complete fungistasis was restored by L-arginine; restoration was concentration dependent, maximal at 2...

  19. Effects of exercise and L-arginine on ventricular remodeling and oxidative stress.

    Science.gov (United States)

    Xu, Xiaohua; Zhao, Weiyan; Lao, Shunhua; Wilson, Bryan S; Erikson, John M; Zhang, John Q

    2010-02-01

    Our aim was to characterize the changes in messenger RNA (mRNA) abundance, protein, and activity levels of the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase, and catalase by exercise training combined with L-arginine after myocardial infarction (MI). L-Arginine (1 g x kg(-1) x d(-1)) and N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg x kg(-1) x d(-1)) were administered in drinking water for 8 wk. Sprague-Dawley rats were randomized to the following groups: sham-operated control (Sham); MI sedentary (Sed); MI exercise (Ex); MI sedentary + L-arginine (Sed + LA); MI exercise + L-arginine (Ex + LA); MI sedentary + L-NAME (Sed + L-NAME); and MI exercise + L-NAME (Ex + L-NAME). The glutathione peroxidase, catalase, and gp91(phox) mRNA levels were comparable among all the groups. The SOD mRNA level was significantly increased in the Ex group (5.43 +/- 0.87) compared with the Sed group (1.74 +/- 0.29), whereas this effect was pronouncedly down-regulated by the L-NAME intervention (2.51 +/- 1.17, P L-arginine treatment when compared with the Sed group. Fractional shortening was significantly preserved in the trained groups compared with their corresponding sedentary groups with or without drug treatments. However, the beneficial effect was not further improved by L-arginine treatment. Our results suggest that exercise training exerts antioxidative effects and attenuates myocardial fibrosis in the MI rats. These improvements, in turn, alleviate cardiac stiffness and preserve post-MI cardiac function. In addition, L-arginine appears to have no additive effect on cardiac function or expression of enzymatic antioxidants.

  20. Oral L-arginine before resistance exercise blunts growth hormone in strength trained males.

    Science.gov (United States)

    Forbes, Scott C; Harber, Vicki; Bell, Gordon J

    2014-04-01

    Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone (GH) concentrations; however, their combined effect is controversial. The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine, GH, GH secretagogues, and IGF-1 in strength trained participants. Fourteen strength trained males (age: 25 ± 4 y; body mass: 81.4 ± 9.0 kg; height: 179.4 ± 6.9 cm; and training experience: 6.3 ± 3.4 y) participated in a randomized double-blind crossover design (separated by ~7 days). Subjects reported to the laboratory at 08:00 in a fasted state, consumed L-arginine (ARG; 0.075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM). Blood samples were collected at rest, before exercise, and at 0, 15, 30, and 60 min of rest-recovery. The ARG condition significantly increased plasma L-arginine concentrations (~120%) while no change was detected in the PLA condition. There were no differences between conditions for GH, GH-releasing hormone, ghrelin, or IGF-1 at any time point. GH-inhibiting hormone was significantly lower in the ARG condition. However, integrated area under the curve for GH was blunted in the ARG condition (L-arginine = 288.4 ± 368.7 vs. placebo = 487.9± 482.0 min·ng·mL1, p L-arginine ingested before resistance exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH. Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop.

  1. Biocatalytic synthesis, antimicrobial properties and toxicity studies of arginine derivative surfactants.

    Science.gov (United States)

    Fait, M Elisa; Garrote, Graciela L; Clapés, Pere; Tanco, Sebastian; Lorenzo, Julia; Morcelle, Susana R

    2015-07-01

    Two novel arginine-based cationic surfactants were synthesized using as biocatalyst papain, an endopeptidase from Carica papaya latex, adsorbed onto polyamide. The classical substrate N (α)-benzoyl-arginine ethyl ester hydrochloride for the determination of cysteine and serine proteases activity was used as the arginine donor, whereas decyl- and dodecylamine were used as nucleophiles for the condensation reaction. Yields higher than 90 and 80 % were achieved for the synthesis of N (α)-benzoyl-arginine decyl amide (Bz-Arg-NHC10) and N (α)-benzoyl-arginine dodecyl amide (Bz-Arg-NHC12), respectively. The purification process was developed in order to make it more sustainable, by using water and ethanol as the main separation solvents in a single cationic exchange chromatographic separation step. Bz-Arg-NHC10 and Bz-Arg-NHC12 proved antimicrobial activity against both Gram-positive and Gram-negative bacteria, revealing their potential use as effective disinfectants as they reduced 99 % the initial bacterial population after only 1 h of contact. The cytotoxic effect towards different cell types of both arginine derivatives was also measured. Bz-Arg-NHCn demonstrated lower haemolytic activity and were less eye-irritating than the commercial cationic surfactant cetrimide. A similar trend could also be observed when cytotoxicity was tested on hepatocytes and fibroblast cell lines: both arginine derivatives were less toxic than cetrimide. All these properties would make the two novel arginine compounds a promising alternative to commercial cationic surfactants, especially for their use as additives in topical formulations.

  2. The Effects of L-arginine on the Hippocampus of Male Rat Fetuses under Maternal Stress

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    Reza Mahmoudi

    2016-01-01

    arginine (1.7±0.15 mm and nonstress (1.6±0.13 mm groups. Discussion: Results indicated that prenatal stress could lead to neurodegeneration of hippocampus and prefrontal cortex of rat fetuses. L-arginine as a precursor of NO synthesis had neuroprotective effect during prenatal stress and could be used an effective treatment for stress.

  3. Kidney Mass Reduction Leads to l-Arginine Metabolism-Dependent Blood Pressure Increase in Mice.

    Science.gov (United States)

    Pillai, Samyuktha Muralidharan; Seebeck, Petra; Fingerhut, Ralph; Huang, Ji; Ming, Xiu-Fen; Yang, Zhihong; Verrey, François

    2018-02-25

    Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l-citrulline, that is used in the kidney to produce l-arginine, was elevated post-UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l-arginine and is a marker for renal failure. Interestingly, the UNX-induced blood pressure increase was prevented by supplementation of the diet with 5% of the l-arginine precursor, l-citrulline. Because l-arginine is metabolized in the kidney and other peripheral tissues by arginase-2, we tested whether the lack of this metabolic pathway also compensates for decreased l-arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase-2 knockout mice (Arg-2 -/- ) neither displayed an increase in asymmetric dimethylarginine and l-citrulline plasma levels nor a significant increase in blood pressure. UNX leads to a small increase in blood pressure that is prevented by l-citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l-arginine metabolism. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

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    A.C. Perez

    1998-06-01

    Full Text Available We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05. In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 µM. Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

  5. The role of arginine metabolic pathway during embryogenesis and germination in maritime pine (Pinus pinaster Ait.).

    Science.gov (United States)

    Llebrés, María-Teresa; Pascual, María-Belén; Debille, Sandrine; Trontin, Jean-François; Harvengt, Luc; Avila, Concepción; Cánovas, Francisco M

    2018-03-01

    Vegetative propagation through somatic embryogenesis is critical in conifer biotechnology towards multivarietal forestry that uses elite varieties to cope with environmental and socio-economic issues. An important and still sub-optimal process during in vitro maturation of somatic embryos (SE) is the biosynthesis and deposition of storage proteins, which are rich in amino acids with high nitrogen (N) content, such as arginine. Mobilization of these N-rich proteins is essential for the germination and production of vigorous somatic seedlings. Somatic embryos accumulate lower levels of N reserves than zygotic embryos (ZE) at a similar stage of development. To understand the molecular basis for this difference, the arginine metabolic pathway has been characterized in maritime pine (Pinus pinaster Ait.). The genes involved in arginine metabolism have been identified and GFP-fusion constructs were used to locate the enzymes in different cellular compartments and clarify their metabolic roles during embryogenesis and germination. Analysis of gene expression during somatic embryo maturation revealed high levels of transcripts for genes involved in the biosynthesis and metabolic utilization of arginine. By contrast, enhanced expression levels were only observed during the last stages of maturation and germination of ZE, consistent with the adequate accumulation and mobilization of protein reserves. These results suggest that arginine metabolism is unbalanced in SE (simultaneous biosynthesis and degradation of arginine) and could explain the lower accumulation of storage proteins observed during the late stages of somatic embryogenesis.

  6. Synthesis and characterization of ZnS quantum dots and application for development of arginine biosensor

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    Neelam Verma

    2017-09-01

    Full Text Available Arginine deiminase co-immobilized with ZnS QDs coupled micro-disk was applied for the sensing of arginine in real and spiked fruit samples. Intracellular arginine deiminase from Lactococcus lactis MTCC 460 was partially purified by ammonium sulphate precipitation and co-immobilized on hydrosol gel disk with ZnS quantum dots. Surface study and topology of immobilized ZnS QDs were characterized by SEM. The size of MPA capped ZnS quantum dots was achieved up to 200 nm. Excitation and emission wavelength of synthesized ZnS QDs was observed to be 259 and 580 nm respectively. Linear range of detection of arginine was found to be 1.0 to 10−4 M and developed biosensor was used to monitor arginine in water melon and pomegranate fruit juices. Main advantage of the developed system is there is no need of pretreatment of sample for the estimation of arginine content.

  7. Effects of various dietary arginine and lysine concentrations on plasma and liver cholesterol concentrations in rats.

    Science.gov (United States)

    Spielmann, Julia; Noatsch, Anne; Brandsch, Corinna; Stangl, Gabriele I; Eder, Klaus

    2008-01-01

    It has been hypothesized that the arginine:lysine ratio of dietary proteins influences cholesterol concentrations in plasma and liver of men and animals. This study was performed to test this hypothesis in rats by using diets with various concentrations of arginine and lysine, differing in their arginine:lysine ratios. Two experiments with growing rats were performed, some of which received diets containing 4.5, 9 or 18 g arginine/kg and 9 or 18 g lysine/kg, respectively, for a period of 21 days. In the first experiment, a cholesterol-free diet was used; in the second experiment, a diet supplemented with cholesterol and sodium cholate as hypercholesterolaemic compounds was used. In experiment 1, increasing the arginine concentration lowered HDL and plasma cholesterol concentration; however, cholesterol concentrations in liver, LDL and VLDL remained unchanged. In experiment 2, increasing the arginine concentration lowered HDL cholesterol and increased liver cholesterol (plysine concentration concerned the effect on VLDL and liver cholesterol concentration, which were both lower in rats fed the diets with 18 g lysine/kg than in those fed the diets with 9 g lysine/kg (parginine:lysine ratio between 0.25 and 2.0 had no influence on cholesterol concentration in LDL and VLDL in both experiments; HDL cholesterol concentration was lowered by increasing this ratio (parginine:lysine ratio causes hypocholesterolaemic effects in rats. Copyright 2008 S. Karger AG, Basel.

  8. tlpA gene expression is required for arginine and bicarbonate chemotaxis in Helicobacter pylori.

    Science.gov (United States)

    Cerda, Oscar A; Núñez-Villena, Felipe; Soto, Sarita E; Ugalde, José Manuel; López-Solís, Remigio; Toledo, Héctor

    2011-01-01

    About half of the human population is infected with Helicobacter pylori, a bacterium causing gastritis, peptic ulcer and progression to gastric cancer. Chemotaxis and flagellar motility are required for colonization and persistence of H. pylori in the gastric mucus layer. It is not completely clear which chemical gradients are used by H. pylori to maintain its position. TlpA, a chemotaxis receptor for arginine/ bicarbonate, has been identified. This study aimed to find out whether tlpA gene expression is required for the chemotactic response to arginine/bicarbonate. Wild-type motile H. pylori ATCC 700392 and H. pylori ATCC 43504, a strain having an interrupted tlpA gene, were used. Also, a tlpA-knockout mutant of H. pylori 700392 (H. pylori 700-tlpA::cat) was produced by homologous recombination. Expression of tlpA was assessed by a Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay. Chemotaxis was measured as a Relative Chemotaxis Response (RCR) by a modified capillary assay. H. pylori 700392 presented chemotaxis to arginine and sodium bicarbonate. H. pylori 700-tlpA::cat showed neither tlpA gene expression nor chemotaxis towards arginine and bicarbonate. Besides confirming that TlpA is a chemotactic receptor for arginine/bicarbonate in H. pylori, this study showed that tlpA gene expression is required for arginine/bicarbonate chemotaxis.

  9. Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity

    Science.gov (United States)

    Cusumano, Zachary T.; Watson, Michael E.

    2014-01-01

    A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stress in vitro. Its expression is enhanced in murine models of infection, suggesting an important role in vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS−/−) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability of S. pyogenes to utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by which S. pyogenes uses its metabolism to modulate innate immunity through depletion of an essential host nutrient. PMID:24144727

  10. Egg quality of hens fed different digestible lysine and arginine levels

    Directory of Open Access Journals (Sweden)

    FB de Carvalho

    2015-03-01

    Full Text Available This experiment aimed at evaluating the influence of the supplementation of digestible lysine and digestible arginine at different ratios in the diet fed to layers between 24 to 44 weeks of age on egg quality. In total,320 Lohmann LSL laying hens were allotted according to a completely randomized design in a 2 x 4factorial arrangement, consisting of two digestible lysine levels (700 or 900 mg/kg of diet and four digestible arginine levels (700, 800, 900,or 1000 mg/kg of diet. Diets contained, therefore, digestible Lys:Arg ratios of 100, 114, 128, and 142 when the diet contained 700 mg digestible lysine per kg of diet, and 78, 89, 100, and 111 when 900 mg digestible lysine per kg was supplemented. The data obtained with digestible arginine levels were fitted to polynomial regression equations, and with digestible lysine, the F test (5% probability was used to compare the means. The following variables were evaluated: egg weight; internal egg quality (yolk percentage and index, albumen percentage, Haugh units, eggshell quality (specific gravity andeggshell percentage; and whole egg, albumen, and yolk solids content. Digestible lysine and arginine interaction did not affect egg quality. Increasing levels of digestible lysine and arginine reduced eggshell quality and albumen solids, respectively. The levels of these amino acids suggested to improveegg quality are 700 mg digestible lysine and 700 mg digestible arginine/kg of feed at a Dig Lys: Dig Arg ratio of 100.

  11. tlpA gene expression is required for arginine and bicarbonate chemotaxis in Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Oscar A Cerda

    2011-01-01

    Full Text Available About half of the human population is infected with Helicobacter pylori, a bacterium causing gastritis, peptic ulcer and progression to gastric cancer. Chemotaxis and flagellar motility are required for colonization and persistence of H. pylori in the gastric mucus layer. It is not completely clear which chemical gradients are used by H. pylori to maintain its position. TlpA, a chemotaxis receptor for arginine/ bicarbonate, has been identified. This study aimed to find out whether tlpA gene expression is required for the chemotactic response to arginine/bicarbonate. Wild-type motile H. pylori ATCC 700392 and H. pylori ATCC 43504, a strain having an interrupted tlpA gene, were used. Also, a tlpA-knockout mutant of H. pylori 700392 (H. pylori 700-tlpA::cat was produced by homologous recombination. Expression of tlpA was assessed by a Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR assay. Chemotaxis was measured as a Relative Chemotaxis Response (RCR by a modified capillary assay. H. pylori 700392 presented chemotaxis to arginine and sodium bicarbonate. H. pylori 700-tlpA::cat showed neither tlpA gene expression nor chemotaxis towards arginine and bicarbonate. Besides confirming that TlpA is a chemotactic receptor for arginine/bicarbonate in H. pylori, this study showed that tlpA gene expression is required for arginine/bicarbonate chemotaxis.

  12. Dietary L-arginine supplementation affects the skeletal longissimus muscle proteome in finishing pigs.

    Science.gov (United States)

    Ma, Xianyong; Zheng, Chuntian; Hu, Youjun; Wang, Li; Yang, Xuefen; Jiang, Zongyong

    2015-01-01

    Forty-eight Duroc x Landrace x Large White gilts were used to determine the relationship between proteome changes of longissimus muscle and intramuscular fat (IMF) content in arginine-supplemented pigs. Beginning at 60 kg BW, pigs were fed a corn- and soybean meal-based diet supplemented or not with 1% L-arginine until they reached a BW of 100 kg. Supplementation with 1% L-arginine did not affect the growth performance or carcass traits, while it increased IMF content by 32% (P supplementation with 1% dietary L-arginine did not change the proportion of SFA and MUFA in muscle lipids. The proteome changes in longissimus muscle between the control and supplemented pigs showed that L-arginine significantly influenced the abundance of proteins related to energy metabolism, fiber type and structure. The increase in IMF content was positively correlated with the increased abundance of slow twitch troponin I (TNNI1) protein and negatively correlated with myosin heavy chain IIb (MyHC IIb) protein content. It is suggested that the proteome changes in longissimus muscle contributed to the greater IMF content in L-arginine supplemented pigs.

  13. Dietary L-arginine supplementation affects the skeletal longissimus muscle proteome in finishing pigs.

    Directory of Open Access Journals (Sweden)

    Xianyong Ma

    Full Text Available Forty-eight Duroc x Landrace x Large White gilts were used to determine the relationship between proteome changes of longissimus muscle and intramuscular fat (IMF content in arginine-supplemented pigs. Beginning at 60 kg BW, pigs were fed a corn- and soybean meal-based diet supplemented or not with 1% L-arginine until they reached a BW of 100 kg. Supplementation with 1% L-arginine did not affect the growth performance or carcass traits, while it increased IMF content by 32% (P < 0.01, it also decreased the drip loss at 48 h post-mortem and the b* meat color value at 24 h post-mortem; supplementation with 1% dietary L-arginine did not change the proportion of SFA and MUFA in muscle lipids. The proteome changes in longissimus muscle between the control and supplemented pigs showed that L-arginine significantly influenced the abundance of proteins related to energy metabolism, fiber type and structure. The increase in IMF content was positively correlated with the increased abundance of slow twitch troponin I (TNNI1 protein and negatively correlated with myosin heavy chain IIb (MyHC IIb protein content. It is suggested that the proteome changes in longissimus muscle contributed to the greater IMF content in L-arginine supplemented pigs.

  14. Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions.

    Science.gov (United States)

    Erdélyi-Bótor, Szilvia; Komáromy, Hedvig; Kamson, David Olayinka; Kovács, Norbert; Perlaki, Gábor; Orsi, Gergely; Molnár, Tihamér; Illes, Zsolt; Nagy, Lajos; Kéki, Sándor; Deli, Gabriella; Bosnyák, Edit; Trauninger, Anita; Pfund, Zoltán

    2017-05-01

    Background/Aim Migraine is a risk factor for the formation of silent brain white matter lesions (WMLs) that are possibly ischemic in nature. Although dysfunction of the L-arginine/nitric oxide (NO) pathway has been associated with oxidative stress and endothelial dysfunction in migraine, its role in WML development has not been specifically investigated. Thus, this prospective study aimed to measure the serum concentrations of the NO substrate L-arginine, the NO synthase inhibitor asymmetric dimethylarginine (ADMA), and the L-arginine transport regulator symmetric dimethylarginine (SDMA) in migraine patients in a headache-free period. Methods All participants underwent MR imaging to assess for the presence of WMLs on fluid-attenuated inversion recovery imaging. Altogether 109 migraine patients (43 with lesions, 66 without lesions) and 46 control individuals were studied. High-performance liquid chromatography was used to quantify L-arginine, ADMA and SDMA serum concentrations. Migraine characteristics were investigated, and participants were screened for risk factors that can lead to elevated serum ADMA levels independent of migraine. Results Migraine patients and controls did not differ in regard to vascular risk factors. Migraineurs with WMLs had a longer disease duration ( p L-arginine serum levels were found in both migraine subgroups compared to controls ( p L-arginine serum levels might reflect an increased demand for NO synthesis.

  15. Dietary L-Arginine Supplementation Affects the Skeletal Longissimus Muscle Proteome in Finishing Pigs

    Science.gov (United States)

    Ma, Xianyong; Zheng, Chuntian; Hu, Youjun; Wang, Li; Yang, Xuefen; Jiang, Zongyong

    2015-01-01

    Forty-eight Duroc x Landrace x Large White gilts were used to determine the relationship between proteome changes of longissimus muscle and intramuscular fat (IMF) content in arginine-supplemented pigs. Beginning at 60 kg BW, pigs were fed a corn- and soybean meal-based diet supplemented or not with 1% L-arginine until they reached a BW of 100 kg. Supplementation with 1% L-arginine did not affect the growth performance or carcass traits, while it increased IMF content by 32% (P L-arginine did not change the proportion of SFA and MUFA in muscle lipids. The proteome changes in longissimus muscle between the control and supplemented pigs showed that L-arginine significantly influenced the abundance of proteins related to energy metabolism, fiber type and structure. The increase in IMF content was positively correlated with the increased abundance of slow twitch troponin I (TNNI1) protein and negatively correlated with myosin heavy chain IIb (MyHC IIb) protein content. It is suggested that the proteome changes in longissimus muscle contributed to the greater IMF content in L-arginine supplemented pigs. PMID:25635834

  16. L-Arginine Pathway in COPD Patients with Acute Exacerbation: A New Potential Biomarker.

    Science.gov (United States)

    Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor; Sarosi, Veronika; Illes, Balazs; Illes, Zsolt; Horvath, Ildiko; Bogar, Lajos; Molnar, Tihamer

    2016-01-01

    Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains a major cause of mortality. Clinical criteria of AECOPD are subjective. Biomarkers for AECOPD may aid in the initiation of early treatment. Increased production of asymmetric and symmetric dimethylarginine (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD. L-arginine metabolites quantified by high-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects. Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p L-arginine, ADMA and SDMA serum levels. In patients with AECOPD, production of ADMA and SDMA are more pronounced presumably due to more severe hypoxic insult. Methylated arginine derivatives in the sera may help early recognition of AECOPD.

  17. L-arginine ingestion after rest and exercise: effects on glucose disposal.

    Science.gov (United States)

    Robinson, Tristan M; Sewell, Dean A; Greenhaff, Paul L

    2003-08-01

    There is considerable interest, both in health and disease, in enhancing postexercise glucose uptake and glycogen resynthesis in skeletal muscle. The amino acid, arginine, is known to stimulate insulin release and enhance glucose-stimulated insulin release. The present investigation examined whether an oral dose of L-arginine (10 g), when given with 70 g carbohydrate (CHO, in the form of simple sugars) improved factors associated with glucose disposal in previously exercised and nonexercised healthy males. The effects of different modes of activity (resistance or cycling exercise) upon these factors were also examined. Whole-blood glucose and serum insulin concentrations after L-arginine + CHO ingestion were not significantly different from the placebo condition (glycine + CHO ingestion) in all experimental treatments (nonexercised, resistance exercise, and cycling exercise). Similarly, CHO oxidation, forearm blood flow, blood pressure, and heart rate during the postingestion period were unaffected by L-arginine + CHO consumption in all three experimental treatments. A 10-g oral dose of L-arginine was found to have no effect on blood glucose disposal in human subjects after oral CHO ingestion, either when rested or after different modes of exercise known to differentially affect glucose disposal. These results suggest that the addition of L-arginine to a CHO beverage would not augment postexercise CHO replenishment in healthy human subjects.

  18. Interaction of arginine, lysine, and guanidine with surface residues of lysozyme: implication to protein stability.

    Science.gov (United States)

    Shah, Dhawal; Shaikh, Abdul Rajjak

    2016-01-01

    Additives are widely used to suppress aggregation of therapeutic proteins. However, the molecular mechanisms of effect of additives to stabilize proteins are still unclear. To understand this, we herein perform molecular dynamics simulations of lysozyme in the presence of three commonly used additives: arginine, lysine, and guanidine. These additives have different effects on stability of proteins and have different structures with some similarities; arginine and lysine have aliphatic side chain, while arginine has a guanidinium group. We analyze atomic contact frequencies to study the interactions of the additives with individual residues of lysozyme. Contact coefficient, quantified from contact frequencies, is helpful in analyzing the interactions with the guanidine groups as well as aliphatic side chains of arginine and lysine. Strong preference for contacts to the additives (over water) is seen for the acidic followed by polar and the aromatic residues. Further analysis suggests that the hydration layer around the protein surface is depleted more in the presence of arginine, followed by lysine and guanidine. Molecular dynamics simulations also reveal that the internal dynamics of protein, as indicated by the lifetimes of the hydrogen bonds within the protein, changes depending on the additives. Particularly, we note that the side-chain hydrogen-bonding patterns within the protein differ with the additives, with several side-chain hydrogen bonds missing in the presence of guanidine. These results collectively indicate that the aliphatic chain of arginine and lysine plays a critical role in the stabilization of the protein.

  19. Growth hormone response to insulin and to arginine in patients with familial hypercholesterolaemia.

    Science.gov (United States)

    Muggeo, M; Tiengo, A; Fedele, D; Crepaldi, G

    1975-01-01

    Human growth hormone (HGH) response to i.v. insulin (0.1 U/kg body weight) and arginine infusion (25 g of L-arginine for 30 min) was studied in 9 patients (5 males and 4 females) with primary familial hypercholesterolaemia and belonging to 4 families. Mean age was 28 +/- 2 years (range 18-36) and body weight was less than 105% of ideal body weight. Glucose tolerance and insulin response to oral glucose were normal in all patients. HGH release after insulin and after arginine was slightly increased as compared to 21 normal controls, but the differences were not significant. Insulin and glucagon response to arginine in these patients was within the normal range. Plasma glucose and free fatty acids were normal after both insulin and arginine. Moreover, no significant correlation was found between fasting cholesterol and HGH peaks after insulin and after arginine, nor between cholesterol and insulin and glucagon responses. Despite marked hyperlipidaemia, HGH-deficient patients examined by other authors never present signs of atherosclerotic disease. Our data suggest that HGH, in the presence of elevated cholesterol levels, might play an important role in the development of atherosclerotic lesions.

  20. L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.

    Science.gov (United States)

    Choe, Chi-un; Nabuurs, Christine; Stockebrand, Malte C; Neu, Axel; Nunes, Patricia; Morellini, Fabio; Sauter, Kathrin; Schillemeit, Stefan; Hermans-Borgmeyer, Irm; Marescau, Bart; Heerschap, Arend; Isbrandt, Dirk

    2013-01-01

    Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine synthesis or distribution include mental retardation and muscular weakness. Human mutations in l-arginine:glycine amidinotransferase (AGAT), the first enzyme of Cr synthesis, lead to severely reduced Cr and guanidinoacetate (GuA) levels. Here, we report the generation and metabolic characterization of AGAT-deficient mice that are devoid of Cr and its precursor GuA. AGAT-deficient mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels and enhanced glucose tolerance. Furthermore, Cr deficiency completely protected from the development of metabolic syndrome caused by diet-induced obesity. Biochemical analyses revealed the chronic Cr-dependent activation of AMP-activated protein kinase (AMPK), which stimulates catabolic pathways in metabolically relevant tissues such as the brain, skeletal muscle, adipose tissue and liver, suggesting a mechanism underlying the metabolic phenotype. In summary, our results show marked metabolic effects of Cr deficiency via the chronic activation of AMPK in a first animal model of AGAT deficiency. In addition to insights into metabolic changes in Cr deficiency syndromes, our genetic model reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus.

  1. Effects of arginine vasopressin on musical working memory.

    Science.gov (United States)

    Granot, Roni Y; Uzefovsky, Florina; Bogopolsky, Helena; Ebstein, Richard P

    2013-01-01

    Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP) and musical working memory (WM). The current study set out to test the influence of intranasal administration (INA) of AVP on musical as compared to verbal WM using a double blind crossover (AVP-placebo) design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo) in a second session, 1 week apart. In each session subjects completed the tonal subtest from Gordon's "Musical Aptitude Profile," the interval subtest from the "Montreal Battery for Evaluation of Amusias (MBEA)," and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV) were higher than for the group receiving vasopressin in the first session (VP) (p music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

  2. Arginine inhibits adsorption of proteins on polystyrene surface.

    Directory of Open Access Journals (Sweden)

    Yui Shikiya

    Full Text Available Nonspecific adsorption of protein on solid surfaces causes a reduction of concentration as well as enzyme inactivation during purification and storage. However, there are no versatile inhibitors of the adsorption between proteins and solid surfaces at low concentrations. Therefore, we examined additives for the prevention of protein adsorption on polystyrene particles (PS particles as a commonly-used material for vessels such as disposable test tubes and microtubes. A protein solution was mixed with PS particles, and then adsorption of protein was monitored by the concentration and activity of protein in the supernatant after centrifugation. Five different proteins bound to PS particles through electrostatic, hydrophobic, and aromatic interactions, causing a decrease in protein concentration and loss of enzyme activity in the supernatant. Among the additives, including arginine hydrochloride (Arg, lysine hydrochloride, guanidine hydrochloride, NaCl, glycine, and glucose, Arg was most effective in preventing the binding of proteins to PS particles as well as activity loss. Moreover, even after the mixing of protein and PS particles, the addition of Arg caused desorption of the bound protein from PS particles. This study demonstrated a new function of Arg, which expands the potential for application of Arg to proteins.

  3. Urinary and metabolic clearances of arginine vasopressin in normal subjects

    International Nuclear Information System (INIS)

    Moses, A.M.; Steciak, E.

    1986-01-01

    Synthetic arginine vasopressin (AVP) was infused into 11 hydrated normal subjects at five different infusion rates ranging from 10 to 350 μU kg -1 min -1 . Each infusion rate was continued for 1 h, and urinary determinations were made on the 30- to 60-min specimens during which time there was no further rise in plasma AVP. Urinary AVP concentrations (μU/ml) and excretion rates (μU/min) increased linearly with increasing infusion rates, and the concentration of AVP in urine increased 120 times more rapid than plasma. Urinary and metabolic clearances of AVP also increased linearly with the maximum urinary clearance being 60.6% of the creatinine clearance. The total metabolic clearance of AVP (including urinary clearance) was 17.8 times that of the urinary clearance of AVP alone. These data clarify the relationships between plasma and urinary AVP in normal hydrated subjects during AVP infusion under steady-state conditions and emphasize the potential advantage of measuring urinary AVP as a monitor of endogenous AVP secretion. AVP was measured by radioimmunoassay

  4. Performance and concentration of amino acids in plasma and urine of young pigs fed diets with excesses of either arginine or lysine.

    Science.gov (United States)

    Southern, L L; Baker, D H

    1982-10-01

    Four experiments were conducted to investigate the arginine x lysine interaction in young pigs. Excess supplemental arginine (.67 to 2% of diet) decreased weight gain and feed intake, but had no effect on efficiency of feed utilization. Lysine supplementation (.5 or 2.5%) did not ameliorate the adverse effects of excess arginine. Decreasing the arginine content to .8% from a level routinely supplied by typical swine diets (1.3%) did not improve pig performance. Excess supplemental arginine increased plasma arginine and ornithine concentrations and decreased plasma lysine and histidine concentrations; several other amino acids were decreased in plasma as well. Feeding 2.8% total dietary arginine resulted in a dramatic increase in urinary excretion of arginine, ornithine, citrulline, lysine, histidine and cystine. From these results it is concluded that the adverse effects of excess arginine represent classic amino acid imbalance rather than amino acid antagonism.

  5. L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

    Science.gov (United States)

    2013-01-01

    Background L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at the level of the endometrium. To this end, this study determined the effect that L-arginine has on apoptosis and cell proliferation in human endometrial RL95-2 cells. Results L-arginine at physiological (200 micromol/L) and supra-physiological (800 micromol/L) concentrations increased cell proliferation at days 2 and 4 post-treatment with a dose-dependent effect being observed on day 2. Additionally, inhibition of nitric oxide (NO) synthase and arginase, which are responsible for the conversion of L-arginine to NO and polyamines, respectively, reduced the proliferative effect of L-arginine. L-arginine also decreased the proportion of cells with TUNEL positive nuclei and increased the ratio of cells with healthy mitochondria compared to cells with a disrupted mitochondrial membrane potential, indicating that L-arginine prevents mitochondrial mediated apoptosis in endometrial RL95-2 cells. Furthermore, exposure to L-arginine did not affect total BAD protein expression; however, L-arginine increased the abundance of phosphorylated BAD protein. Conclusions In summary, L-arginine added to the culture media at physiological (200 micromol/L) and supraphysiological concentrations (800 micromol/L) enhanced endometrial RL95-2 cell proliferation through mechanisms mediated by NO and polyamine biosynthesis. In addition, L-arginine reduced endometrial RL95-2 mitochondrial mediated apoptosis through increased phosphorylation of BAD protein. PMID:23442442

  6. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the “L-arginine paradox”

    International Nuclear Information System (INIS)

    Shin, Soyoung; Mohan, Srinidi; Fung, Ho-Leung

    2011-01-01

    Highlights: ► Our findings provide a possible solution to the “L-arginine paradox”. ► Extracellular L-arginine concentration is the major determinant of NO production. ► Cellular L-arginine action is limited by cellular ARG transport, not the K m of NOS. ► We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of 15 N 4 -ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, 15 N 4 -ARG, dimethylarginines, and L-citrulline by an LC–MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by 15 N-nitrite or estimated 15 N 3 -citrulline concentrations when 15 N 4 -ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced 15 N 4 -ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by 15 N-nitrite, total nitrite and 15 N 3 -citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside the cell, ARG can no longer gain access to the membrane-bound eNOS. These observations indicate that the “L-arginine paradox” should not consider intracellular ARG

  7. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the 'L-arginine paradox'

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Soyoung; Mohan, Srinidi [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Fung, Ho-Leung, E-mail: hlfung@buffalo.edu [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Our findings provide a possible solution to the 'L-arginine paradox'. Black-Right-Pointing-Pointer Extracellular L-arginine concentration is the major determinant of NO production. Black-Right-Pointing-Pointer Cellular L-arginine action is limited by cellular ARG transport, not the K{sub m} of NOS. Black-Right-Pointing-Pointer We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of {sup 15}N{sub 4}-ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, {sup 15}N{sub 4}-ARG, dimethylarginines, and L-citrulline by an LC-MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by{sup 15}N-nitrite or estimated {sup 15}N{sub 3}-citrulline concentrations when {sup 15}N{sub 4}-ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced {sup 15}N{sub 4}-ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by {sup 15}N-nitrite, total nitrite and {sup 15}N{sub 3}-citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside

  8. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages

    Directory of Open Access Journals (Sweden)

    Meera eRath

    2014-10-01

    Full Text Available Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS, which metabolizes arginine to nitric oxide (NO and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the enzyme arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway limits arginine availability for NO synthesis and ornithine itself can further feed into the important downstream pathways of polyamine and proline syntheses, which are important for cellular proliferation and tissue repair. M1 versus M2 polarization leads to opposing outcomes of inflammatory reactions, but depending on the context, M1 and M2 macrophages can be both pro- and antiinflammatory. Notably, M1/M2 macrophage polarization can be driven by microbial infection or innate danger signals without any influence of adaptive immune cells, secondarily driving the T helper (Th1/Th2 polarization of the evolving adaptive immune response. Since both arginine metabolic pathways cross-inhibit each other on the level of the respective arginine break-down products and Th1 and Th2 lymphocytes can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this forms the basis of a self-sustaining M1/M2 polarization of the whole immune response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is therefore central to find new possibilities to manipulate immune responses in infection, autoimmune diseases, chronic inflammatory conditions and cancer.

  9. Clinical Outcome And Arginine Serum of Acute Ischemic Stroke Patients Supplemented by Snakehead Fish Extract

    Science.gov (United States)

    Pudjonarko, Dwi; Retnaningsih; Abidin, Zainal

    2018-02-01

    Background: Levels of arginine associated with clinical outcome in acute ischemic stroke (AIS). Arginine is a protein needed to synthesis nitric oxide (NO), a potential vasodilator and antioxidant. Snakehead fish is a source of protein which has antioxidant activity. Snakehead fish contains mineral, vitamin, and amino acids. One of the amino acids that were found quite high in snakehead fish extract is arginine. The aim of this study was done to determine the effect of snakehead fish extracts (SFE) on serum arginin levels and clinical outcome of AIS patients. Methods: It was double-blind randomized pretest-posttest control group design, with. AIS patients were divided into two groups i.e. snakehead fish extracts (SFE) and control. SFE group were administered 15 grams SFE for 7 days . Arginine serum levels and clinical outcome (measured by National Institute of Health Stroke Scale = NIHSS) were measured before and after treatment, other related factors were also analyzed in Logistic regression. Results: A total of 42 subjects who were performed random allocation as SFE or control group. There was no differences in subject characteristics between the two groups. There was a differences Δ arginine serum levels between SFE and control (33.6±19.95 μmol/L 0.3±2.51 μmol/L p<0.001). Change in NIHSS score in SFE improved significantly compared to the control group (4.14 ± 2.03; 2.52 ± 1.81;p=0.009 ). Logistic regression analysis showed only female gender factor that affected on improvement of NIHSS (OR=7; p=0,01). Conclusion: There is Clinical outcome improvement and enhancement of arginine serum levels in AIS patient with snakehead fish extract supplementation.

  10. Diabetic nephropathy is resistant to oral L-arginine or L-citrulline supplementation.

    Science.gov (United States)

    You, Hanning; Gao, Ting; Cooper, Timothy K; Morris, Sidney M; Awad, Alaa S

    2014-12-01

    Our recent publication showed that pharmacological blockade of arginases confers kidney protection in diabetic nephropathy via a nitric oxide (NO) synthase (NOS)3-dependent mechanism. Arginase competes with endothelial NOS (eNOS) for the common substrate L-arginine. Lack of L-arginine results in reduced NO production and eNOS uncoupling, which lead to endothelial dysfunction. Therefore, we hypothesized that L-arginine or L-citrulline supplementation would ameliorate diabetic nephropathy. DBA mice injected with multiple low doses of vehicle or streptozotocin (50 mg/kg ip for 5 days) were provided drinking water with or without L-arginine (1.5%, 6.05 g·kg(-1)·day(-1)) or L-citrulline (1.66%, 5.73 g·kg(-1)·day(-1)) for 9 wk. Nonsupplemented diabetic mice showed significant increases in albuminuria, blood urea nitrogen, glomerular histopathological changes, kidney macrophage recruitment, kidney TNF-α and fibronectin mRNA expression, kidney arginase activity, kidney arginase-2 protein expression, and urinary oxidative stress along with a significant reduction of nephrin and eNOS protein expression and kidney nitrite + nitrate compared with normal mice after 9 wk of diabetes. Surprisingly, L-arginine or L-citrulline supplementation in diabetic mice did not affect any of these parameters despite greatly increasing kidney and plasma arginine levels. These findings demonstrate that chronic L-arginine or L-citrulline supplementation does not prevent or reduce renal injury in a model of type 1 diabetes. Copyright © 2014 the American Physiological Society.

  11. Expression pattern of a nuclear encoded mitochondrial arginine-ornithine translocator gene from Arabidopsis

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    Schneider Anja

    2003-01-01

    Full Text Available Abstract Background Arginine and citrulline serve as nitrogen storage forms, but are also involved in biosynthetic and catabolic pathways. Metabolism of arginine, citrulline and ornithine is distributed between mitochondria and cytosol. For the shuttle of intermediates between cytosol and mitochondria transporters present on the inner mitochondrial membrane are required. Yeast contains a mitochondrial translocator for ornithine and arginine, Ort1p/Arg11p. Ort1p/Arg11p is a member of the mitochondrial carrier family (MCF essential for ornithine export from mitochondria. The yeast arg11 mutant, which is deficient in Ort1p/Arg11p grows poorly on media lacking arginine. Results High-level expression of a nuclear encoded Arabidopsis thaliana homolog (AtmBAC2 of Ort1p/Arg11p was able to suppress the growth deficiency of arg11. RT-PCR analysis demonstrated expression of AtmBAC2 in all tissues with highest levels in flowers. Promoter-GUS fusions showed preferential expression in flowers, i.e. pollen, in the vasculature of siliques and in aborted seeds. Variable expression was observed in leaf vasculature. Induction of the promoter was not observed during the first two weeks in seedlings grown on media containing NH4NO3, arginine or ornithine as sole nitrogen sources. Conclusion AtmBAC2 was isolated as a mitochondrial transporter for arginine in Arabidopsis. The absence of expression in developing seeds and in cotyledons of seedlings indicates that other transporters are responsible for storage and mobilization of arginine in seeds.

  12. Amniotic Fluid Arginine from Gestational Weeks 13 to 15 Is a Predictor of Birth Weight, Length, and Head Circumference

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    Astrid Bjørke-Jenssen

    2017-12-01

    Full Text Available Arginine is a constituent of proteins and a precursor for polyamines and nitric oxide, and is essential for placentation, angiogenesis, and growth. Maternal plasma arginine concentrations are found to be lower in pregnancies complicated by fetal growth restriction, and arginine supplementation in later pregnancy is reported to increase birth weight. We measured arginine and the metabolites asymmetric dimethylarginine (ADMA and symmetric dimethylarginine (SDMA in the amniotic fluid obtained in pregnancy weeks 13 to 15 from 363 pregnancies with a documented normal outcome and related the concentrations to birth weight, length, and head circumference. Arginine was higher in the amniotic fluid from female (mean 40.8 (SD 10.6 µmol/L compared to male fetuses (37.4 (SD 11.2 µmol/L, p = 0.003. Despite the gender difference, arginine in the amniotic fluid from gestational weeks 13–15 was the strongest predictor for birth weight, length, and head circumference. ADMA was a strong predictor for birth weight and length, SDMA for birth weight, while Arg/ADMA and Arg/SDMA only predicted head circumference in multiple linear regression models. Due to increased arginine demands, pregnancy is considered a state of relative arginine deficiency. Our findings reflect the importance of a good maternal arginine status in early pregnancy, an observation that should be evaluated in an intervention study.

  13. Deprivation of L-Arginine Induces Oxidative Stress Mediated Apoptosis in Leishmania donovani Promastigotes: Contribution of the Polyamine Pathway

    Science.gov (United States)

    Mandal, Abhishek; Das, Sushmita; Roy, Saptarshi; Ghosh, Ayan Kumar; Sardar, Abul Hasan; Verma, Sudha; Saini, Savita; Singh, Ruby; Abhishek, Kumar; Kumar, Ajay; Mandal, Chitra; Das, Pradeep

    2016-01-01

    The growth and survival of intracellular parasites depends on the availability of extracellular nutrients. Deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. To further understand the relationship, the mechanistic role of L-arginine in regulation of redox mediated survival of Leishmania donovani promastigotes was investigated. L-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferation and increase L-arginine uptake. Relative expression of enzymes, involved in L-arginine metabolism, which leads to polyamine and trypanothione biosynthesis, were downregulated causing decreased production of polyamines in L-arginine deprived parasites and cell death. The resultant increase in reactive oxygen species (ROS), due to L-arginine deprivation, correlated with increased NADP+/NADPH ratio, decreased superoxide dismutase (SOD) level, increased lipid peroxidation and reduced thiol content. A deficiency of L-arginine triggered phosphatidyl serine externalization, a change in mitochondrial membrane potential, release of intracellular calcium and cytochrome-c. This finally led to DNA damage in Leishmania promastigotes. In summary, the growth and survival of Leishmania depends on the availability of extracellular L-arginine. In its absence the parasite undergoes ROS mediated, caspase-independent apoptosis-like cell death. Therefore, L-arginine metabolism pathway could be a probable target for controlling the growth of Leishmania parasites and disease pathogenesis. PMID:26808657

  14. An Unexpected Location of the Arginine Catabolic Mobile Element (ACME) in a USA300-Related MRSA Strain

    DEFF Research Database (Denmark)

    Damkjær Bartels, Mette; Hansen, Lars H.; Boye, Kit

    2011-01-01

    In methicillin resistant Staphylococcus aureus (MRSA), the arginine catabolic mobile element (ACME) was initially described in USA300 (t008-ST8) where it is located downstream of the staphylococcal cassette chromosome mec (SCCmec). A common health-care associated MRSA in Copenhagen, Denmark (t024...... of SCCmec, M1 had two new DR between the orfX gene and the J3 region of the SCCmec. The region between the orfX DR (DR1) and DR2 contained the ccrAB4 genes. An ACME II-like element was located between DR2 and DR3. The entire 26,468 bp sequence between DR1 and DR3 was highly similar to parts of the ACME...... composite island of S. epidermidis strain ATCC12228. Sequencing of an ACME negative t024-ST8 strain (M299) showed that DR1 and the sequence between DR1 and DR3 was missing. The finding of a mobile ACME II-like element inserted downstream of orfX and upstream of SCCmec indicates a novel recombination between...

  15. Chimpanzee Personality and the Arginine Vasopressin Receptor 1A Genotype.

    Science.gov (United States)

    Wilson, V A D; Weiss, A; Humle, T; Morimura, N; Udono, T; Idani, G; Matsuzawa, T; Hirata, S; Inoue-Murayama, M

    2017-03-01

    Polymorphisms of the arginine vasopressin receptor 1a (AVPR1a) gene have been linked to various measures related to human social behavior, including sibling conflict and agreeableness. In chimpanzees, AVPR1a polymorphisms have been associated with traits important for social interactions, including sociability, joint attention, dominance, conscientiousness, and hierarchical personality dimensions named low alpha/stability, disinhibition, and negative emotionality/low dominance. We examined associations between AVPR1a and six personality domains and hierarchical personality dimensions in 129 chimpanzees (Pan troglodytes) living in Japan or in a sanctuary in Guinea. We fit three linear and three animal models. The first model included genotype, the second included sex and genotype, and the third included genotype, sex, and sex × genotype. All personality phenotypes were heritable. Chimpanzees possessing the long form of the allele were higher in conscientiousness, but only in models that did not include the other predictors; however, additional analyses suggested that this may have been a consequence of study design. In animal models that included sex and sex × genotype, chimpanzees homozygous for the short form of the allele were higher in extraversion. Taken with the findings of previous studies of chimpanzees and humans, the findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression. The direction of the association between AVPR1a genotype and extraversion ran counter to what one would expect if AVPR1a was related to social behaviors. These results help us further understand the genetic basis of personality in chimpanzees.

  16. Transsulfuration pathway thiols and methylated arginines: the Hunter Community Study.

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    Arduino A Mangoni

    Full Text Available Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH activity] and with symmetric dimethylarginine (SDMA. We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS, and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR = 64 (60-70 years].REGRESSION ANALYSIS SHOWED THAT: a age (P = 0.001, gender (P = 0.03, lower estimated glomerular filtration rate (eGFR, P = 0.08, body mass index (P = 0.008, treatment with beta-blockers (P = 0.03, homocysteine (P = 0.02, and glutamylcysteine (P = 0.003 were independently associated with higher ADMA concentrations; and b age (P = 0.001, absence of diabetes (P = 0.001, lower body mass index (P = 0.01, lower eGFR (P<0.001, cysteine (P = 0.007, and glutamylcysteine (P < 0.001 were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations.After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA and/or cationic amino acid transport requires further investigations.

  17. Effects of Arginine Vasopressin on musical short-term memory

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    Roni Y. Granot

    2013-10-01

    Full Text Available Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP and musical working memory (WM. The current study set out to test the influence of intranasal administration (INA of AVP on musical as compared to verbal WM using a double blind crossover (AVP – placebo design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo in a second session, one week apart. In each session subjects completed the tonal subtest from Gordon's Musical Aptitude Profile, the interval subtest from the Montreal Battery for Evaluation of Amusias (MBEA, and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV were higher than for the group receiving vasopressin in the first session (VP (p < .05 with no main Session effect nor Group * Session interaction. In the Gordon test there was a main Session effect (p < .05 with scores higher in the second as compared to the first session, a marginal main Group effect (p = .093 and a marginal Group X Session interaction (p = 0.88. In addition we found that the group that received AVP in the first session scored higher on scales indicative of happiness, and alertness on the Positive and Negative Affect Scale, (PANAS. Only in this group and only in the music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

  18. Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells

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    Mirick Gary

    2009-04-01

    Full Text Available Abstract Background A variety of arginine-rich peptide sequences similar to those found in viral proteins have been conjugated to other molecules to facilitate their transport into the cytoplasm and nucleus of targeted cells. The selective high affinity ligand (SHAL (DvLPBaPPP2LLDo, which was developed to bind only to cells expressing HLA-DR10, has been conjugated to one of these peptide transduction domains, hexa-arginine, to assess the impact of the peptide on SHAL uptake and internalization by Raji cells, a B-cell lymphoma. Results An analog of the SHAL (DvLPBaPPP2LLDo containing a hexa-arginine peptide was created by adding six D-arginine residues sequentially to a lysine inserted in the SHAL's linker. SHAL binding, internalization and residualization by Raji cells expressing HLA-DR10 were examined using whole cell binding assays and confocal microscopy. Raji cells were observed to bind two fold more 111In-labeled hexa-arginine SHAL analog than Raji cells treated with the parent SHAL. Three fold more hexa-arginine SHAL remained associated with the Raji cells after washing, suggesting that the peptide also enhanced residualization of the 111In transported into cells. Confocal microscopy showed both SHALs localized in the cytoplasm of Raji cells, whereas a fraction of the hexa-arginine SHAL localized in the nucleus. Conclusion The incorporation of a hexa-D-arginine peptide into the linker of the SHAL (DvLPBaPPP2LLDo enhanced both the uptake and residualization of the SHAL analog by Raji cells. In contrast to the abundant cell surface binding observed with Lym-1 antibody, the majority of (DvLPBaPPP2LArg6AcLLDo and the parent SHAL were internalized. Some of the internalized hexa-arginine SHAL analog was also associated with the nucleus. These results demonstrate that several important SHAL properties, including uptake, internalization, retention and possibly intracellular distribution, can be enhanced or modified by conjugating the SHALs to a

  19. l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy.

    Science.gov (United States)

    Szabo, P; Lantos, J; Nagy, L; Keki, S; Volgyi, E; Menyhei, G; Illes, Z; Molnar, T

    2016-12-01

    Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis and is a marker of atherosclerosis. This study examined the correlation between pre-operative l-arginine and ADMA concentration during carotid endarterectomy (CEA), and jugular lactate indicating anaerobic cerebral metabolism, jugular S100B reflecting blood-brain barrier integrity, and with factors of surgical intervention. The concentration of l-arginine, ADMA, and symmetric dimethylarginine was measured in blood taken under regional anaesthesia from the radial artery of 55 patients prior to CEA. Blood gas parameters, concentration of lactate, and S100B were also serially measured in blood taken from both the radial artery and the jugular bulb before and after carotid clamping, and after release of the clamp. To estimate anaerobic metabolism, the jugulo-arterial ratio of CO 2 gap/oxygen extraction was calculated. Positive correlation was found between pre-operative ADMA levels and the ratio of jugulo-arterial CO 2 gap/oxygen extraction during clamp and reperfusion (p = .005 and p = .01, respectively). An inverse correlation was found between the pre-operative l-arginine concentration and jugular lactate at each time point (both p = .002). The critical pre-operative level of l-arginine was determined by receiver operator curve analysis. If l-arginine was below the cutoff value of 35 μmol/L, jugular S100B concentration was higher 24 h post-operatively (p = .03), and jugular lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range 42.3-74.5 μmol/L]; p = .002). High pre-operative ADMA concentration predicts poor cerebral perfusion indicated by elevated jugulo-arterial CO 2 gap/oxygen extraction. Low pre-operative l-arginine

  20. Comparative study of two ATP : L-arginine phosphotransferases of molecular weight 84 000.

    Science.gov (United States)

    Thiem, N V; Lacombe, G; Thoai, N V

    1975-01-23

    Solen ensisensis muscle arginine kinase (ATP : L-arginine phosphotransferase, EC 2.7.3.3) was isolated in an homogeneous state. Its molecular weight was found to be about 80 000. The properties of this enzyme were compared with those of arginine kinase from Sipunculus nudus, an enzyme which also has a molecular weight of about 80 000. Both enzymes have several reactive thiol groups (8 thiol groups in the Solen kinase and 12 in the Sipunculus enzyme were titrateable with 5,5'-dithio-bis-(2-nitrobenzoic) acid and histidine residues (both enzymes have 6 reactive histidine residues). These kinases were, therefore, highly susceptible to oxidation. Both enzymes show the same pH optimum and absolute specificity towards the guanidine substrate, L-arginine. The reaction kinetics of both enzymes are of the sequential type. In the presence of alpha-aminoacids of Mg2+-ADP, similar spectral effects were obtained. The enzymes differ in their enzymic activities and in their rate of recovery following urea denaturation. The most important difference that appeared to be a special feature of the Sipunculus enzyme is that the spectrum of the Mg2+-ADP-enzyme complex is strongly intensified by L-arginine.

  1. PKCepsilon stimulated arginine methylation of RIP140 for its nuclear-cytoplasmic export in adipocyte differentiation.

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    Pawan Gupta

    2008-07-01

    Full Text Available Receptor interacting protein 140 (RIP140 is a versatile transcriptional co-repressor that plays roles in diverse metabolic processes including fat accumulation in adipocytes. Previously we identified three methylated arginine residues in RIP140, which rendered its export to the cytoplasm; but it was unclear what triggered RIP140 arginine methylation.In this study, we determined the activated PKCepsilon as the specific trigger for RIP140 arginine methylation and its subsequent export. We identified two PKCepsilon-phosphorylated residues of RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the nuclear gene-repressive activity of RIP140 was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation was effectively rescued by the phosphorylation-deficient mutant RIP140 that resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140 that was exported to the cytoplasm.This study uncovers a novel means, via a cascade of protein modifications, to inactivate, or suppress, the nuclear action of an important transcription coregulator RIP140, and delineates the first specific phosphorylation-arginine methylation cascade that could alter protein subcellular distribution and biological activity.

  2. Apple snack enriched with L-arginine using vacuum impregnation/ohmic heating technology.

    Science.gov (United States)

    Moreno, Jorge; Echeverria, Julian; Silva, Andrea; Escudero, Andrea; Petzold, Guillermo; Mella, Karla; Escudero, Carlos

    2017-07-01

    Modern life has created a high demand for functional food, and in this context, emerging technologies such as vacuum impregnation and ohmic heating have been applied to generate functional foods. The aim of this research was to enrich the content of the semi-essential amino acid L-arginine in apple cubes using vacuum impregnation, conventional heating, and ohmic heating. Additionally, combined vacuum impregnation/conventional heating and vacuum impregnation/ohmic heating treatments were evaluated. The above treatments were applied at 30, 40 and 50  ℃ and combined with air-drying at 40 ℃ in order to obtain an apple snack rich in L-arginine. Both the impregnation kinetics of L-arginine and sample color were evaluated. The impregnated samples created using vacuum impregnation/ohmic heating at 50 ℃ presented a high content of L-arginine, an effect attributed primarily to electropermeabilization. Overall, vacuum impregnation/ohmic heating treatment at 50 ℃, followed by drying at 40 ℃, was the best process for obtaining an apple snack rich in L-arginine.

  3. Differences in DNA condensation and release by lysine and arginine homopeptides govern their DNA delivery efficiencies.

    Science.gov (United States)

    Mann, Anita; Thakur, Garima; Shukla, Vasundhara; Singh, Anand Kamal; Khanduri, Richa; Naik, Rangeetha; Jiang, Yang; Kalra, Namita; Dwarakanath, B S; Langel, Ulo; Ganguli, Munia

    2011-10-03

    Designing of nanocarriers that can efficiently deliver therapeutic DNA payload and allow its smooth intracellular release for transgene expression is still a major constraint. The optimization of DNA nanocarriers requires thorough understanding of the chemical and structural characteristics of the vector-nucleic acid complexes and its correlation with the cellular entry, intracellular state and transfection efficiency. L-lysine and L-arginine based cationic peptides alone or in conjugation with other vectors are known to be putative DNA delivery agents. Here we have used L-lysine and L-arginine homopeptides of three different lengths and probed their DNA condensation and release properties by using a multitude of biophysical techniques including fluorescence spectroscopy, gel electrophoresis and atomic force microscopy. Our results clearly showed that although both lysine and arginine based homopeptides condense DNA via electrostatic interactions, they follow different pattern of DNA condensation and release in vitro. While lysine homopeptides condense DNA to form both monomolecular and multimolecular complexes and show differential release of DNA in vitro depending on the peptide length, arginine homopeptides predominantly form multimolecular complexes and show complete DNA release for all peptide lengths. The cellular uptake of the complexes and their intracellular state (as observed through flow cytometry and fluorescence microscopy) seem to be controlled by the peptide chemistry. The difference in the transfection efficiency of lysine and arginine homopeptides has been rationalized in light of these observations.

  4. [Arginine and lysine as products of basic carboxypeptidase activity associated with fibrinolysis].

    Science.gov (United States)

    Zhloba, A A; Subbotina, T F; Lupan, D S; Bogova, V A; Kusheleva, O A

    2013-01-01

    Blood carboxypeptidases play an important role in the regulation of fibrinolysis. We have proposed here the method for the assay of blood carboxypeptidase activity associated with coagulation/fibrinolysis using the natural substrate fibrin and the detection of basic amino acids arginine and lysine as products in the conditions close to those in vivo. Plasma samples from 15 patients with arterial hypertension were investigated. The coagulation and subsequent fibrinolysis were initiated by addition of standard doses of thrombin and tissue plasminogen activator, respectively. Arginine and lysine concentrations before, during, and after completion of fibrinolysis were determined using HPLC. The parameters of fibrinolysis were evaluated by clot turbidity assay. Fibrinolysis led to a large and significant increase in concentrations of arginine and lysine in the incubation mixture by 101 and 81%, respectively. The duration of fibrinolysis initiation significantly correlated to the degree of increase of these amino acids: r(s) = -0.733 and -0.761 for arginine and lysine, respectively (p arginine generation had two maximums: at the beginning of clot lysis and at his end, whereas the liberation of lysine occurred mainly at the middle of fibrinolysis. Thus, the carboxypeptidase activity associated with fibrinolysis can be considered as a local source of the essential aminoacids.

  5. EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

    Science.gov (United States)

    Iacob, Andreea-Teodora; Drăgan, Maria; Constantin, Sandra; Lupaşcu, Florentina; Confederat, Luminiţa; Buron, F; Routier, S; Profire, Lenuţa

    2016-01-01

    L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

  6. Short Arginine Motifs Drive Protein Stickiness in the Escherichia coli Cytoplasm.

    Science.gov (United States)

    Kyne, Ciara; Crowley, Peter B

    2017-09-19

    Although essential to numerous biotech applications, knowledge of molecular recognition by arginine-rich motifs in live cells remains limited. 1 H, 15 N HSQC and 19 F NMR spectroscopies were used to investigate the effects of C-terminal -GR n (n = 1-5) motifs on GB1 interactions in Escherichia coli cells and cell extracts. While the "biologically inert" GB1 yields high-quality in-cell spectra, the -GR n fusions with n = 4 or 5 were undetectable. This result suggests that a tetra-arginine motif is sufficient to drive interactions between a test protein and macromolecules in the E. coli cytoplasm. The inclusion of a 12 residue flexible linker between GB1 and the -GR 5 motif did not improve detection of the "inert" domain. In contrast, all of the constructs were detectable in cell lysates and extracts, suggesting that the arginine-mediated complexes were weak. Together these data reveal the significance of weak interactions between short arginine-rich motifs and the E. coli cytoplasm and demonstrate the potential of such motifs to modify protein interactions in living cells. These interactions must be considered in the design of (in vivo) nanoscale assemblies that rely on arginine-rich sequences.

  7. The impact of arginine-modified chitosan-DNA nanoparticles on the function of macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Liu Lanxia; Bai Yuanyuan; Song Chunni; Zhu Dunwan; Song Liping; Zhang Hailing; Dong Xia; Leng Xigang, E-mail: lengxg@bme.org.c [Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Laboratory of Bioengineering (China)

    2010-06-15

    It has been demonstrated that incorporation of arginine moieties into chitosan significantly elevates the transgenic efficacy of the chitosan. However, little is known about the impact of arginine-modified chitosan on the function of macrophages, which play a vitally important role in the inflammatory response of the body to foreign substances, especially particulate substances. This study was designed to investigate the impact of arginine-modified chitosan/DNA nanoparticles on the function of the murine macrophage through observation of phagocytic activity and production of pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-10, IL-12, and TNF-{alpha}). Results showed that both chitosan/DNA nanoparticles and arginine-modified chitosan/DNA nanoparticles, containing 20 {mu}g/mL DNA, were internalized by almost all the macrophages in contact. This led to no significant changes, compared to the non-exposure group, in production of cytokines and phagocytic activity of the macrophages 24 h post co-incubation, whereas exposure to LPS induced obviously elevated cytokine production and phagocytic activity, suggesting that incorporation of arginine moieties into chitosan does not have a negative impact on the function of the macrophages.

  8. Malaria in pregnancy alters l-arginine bioavailability and placental vascular development.

    Science.gov (United States)

    McDonald, Chloe R; Cahill, Lindsay S; Gamble, Joel R; Elphinstone, Robyn; Gazdzinski, Lisa M; Zhong, Kathleen J Y; Philson, Adrienne C; Madanitsa, Mwayiwawo; Kalilani-Phiri, Linda; Mwapasa, Victor; Ter Kuile, Feiko O; Sled, John G; Conroy, Andrea L; Kain, Kevin C

    2018-03-07

    Reducing adverse birth outcomes due to malaria in pregnancy (MIP) is a global health priority. However, there are few safe and effective interventions. l-Arginine is an essential amino acid in pregnancy and an immediate precursor in the biosynthesis of nitric oxide (NO), but there are limited data on the impact of MIP on NO biogenesis. We hypothesized that hypoarginemia contributes to the pathophysiology of MIP and that l-arginine supplementation would improve birth outcomes. In a prospective study of pregnant Malawian women, we show that MIP was associated with lower concentrations of l-arginine and higher concentrations of endogenous inhibitors of NO biosynthesis, asymmetric and symmetric dimethylarginine, which were associated with adverse birth outcomes. In a model of experimental MIP, l-arginine supplementation in dams improved birth outcomes (decreased stillbirth and increased birth weight) compared with controls. The mechanism of action was via normalized angiogenic pathways and enhanced placental vascular development, as visualized by placental microcomputerized tomography imaging. These data define a role for dysregulation of NO biosynthetic pathways in the pathogenesis of MIP and support the evaluation of interventions to enhance l-arginine bioavailability as strategies to improve birth outcomes. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  9. Effect of levo-dopa, arginine and exercise on pituitary growth hormone (GH) secretion

    International Nuclear Information System (INIS)

    Li Zhiyong; Li Xinghua; Ji Xuejing; Zan Kun; Gao Lili

    2004-01-01

    Objective: To assess the stimulation effect on GH secretion with different agents (levo-dopa, arginine, exercise) in dwarf subjects. Methods: Growth hormone provocative tests were performed with levo-dopa (42 times), arginine (33) and standardized exercise (35) in 78 subjects classified as dwarfs. Serum GH levels were determined with RIA before the test and several times (at 30 min, intervals) afterwards with the peak value noted. The test results were divided into 3 categories: 1) peak value 10 ng/ml, test positive (no GH deficiency). Results: Peak values of serum GH after stimulation test with respective agents were: levo-dopa 14.09 ± 9.62 ng/ml, arginine 13.77 ± 6.83 ng/ml and exercise 12.68 ± 7.81 ng/ml with no significant differences among them. Positive rate after drug stimulation was significantly higher than that after exercise: levo-dopa 35.71% (15/42), arginine 36.36% (12/33) vs exercise 14.20% (5/35) P 0.05). Conclusion: Diagnosis of GH deficiency (stimulation test negative) is best established after two negative provocative tests with different stimulant each time. Levo-dopa and arginine may be the drug of choice. (authors)

  10. Camphorquinone-10-sulfonic acid and derivatives: convenient reagents for reversible modification of arginine residues.

    Science.gov (United States)

    Pande, C S; Pelzig, M; Glass, J D

    1980-02-01

    Camphorquinone-10-sulfonic acid hydrate was prepared by the action of selenous acid on camphor-10-sulfonic acid. Camphorquinone-10-sulfonylnorleucine was prepared either from the sulfonic acid via the sulfonyl chloride or by selenous acid oxidation of camphor-10-sulfonylnorleucine. These reagents are useful for specific, reversible modification of the guanidino groups of arginine residues. Camphorquinonesulfonic acid is a crystalline water-soluble reagent that is especially suitable for use with small arginine-containing molecules, because the sulfonic acid group of the reagent is a convenient handle for analytical and preparative separation of products. Camphorquinonesulfonylnorleucine is more useful for work with large polypeptides and proteins, because hydrolysates of modified proteins may be analyzed for norleucine to determine the extent of arginine modification. The adducts of the camphorquinone derivatives with the guanidino group are stable to 0.5 M hydroxylamine solutions at pH 7, the recommended conditions for cleavage of the corresponding cyclohexanedione adducts. At pH 8-9 the adducts of the camphorquinone derivatives with the guanidino group are cleaved by o-phenylenediamine. The modification and regeneration of arginine, of the dipeptide arginylaspartic acid, of ribonuclease S-peptide, and of soybean trypsin inhibitor are presented as demonstrations of the use of the reagents. The use of camphorquinonesulfonyl chloride to prepare polymers containing arginine-specific ligands is discussed.

  11. A UV-induced mutation in neurospora that affects translational regulation in response to arginine

    International Nuclear Information System (INIS)

    Freitag, M.; Dighde, N.; Sachs, M.S.

    1996-01-01

    The Neurospora crassa arg-2 gene encodes the small subunit of arginine-specific carbamoyl phosphate synthetase. The levels of arg-2 mRNA and mRNA translation are negatively regulated by arginine. An upstream open reading frame (uORF) in the transcript's 5' region has been implicated in arginine-specific control. An arg-2-hph fusion gene encoding hygromycin phosphotransferase conferred arginine-regulated resistance to hygromycin when introduced into N. crassa. We used an arg-2-hph strain to select for UV-induced mutants that grew in the presence of hygromycin and arginine, and we isolated 46 mutants that had either of two phenotypes. One phenotype indicated altered expression of both arg-2-hph and arg-2 genes; the other, altered expression of arg-2-hph but not arg-2. One of the latter mutations, which was genetically closely linked to arg-2-hph, was recovered from the 5' region of the arg-2-hph gene using PCR Sequence analyses and transformation experiments revealed a mutation at uORF codon 12 (Asp to Asn) that abrogated negative regulation. Examination of the distribution of ribosomes on arg-2-hph transcripts showed that loss of regulation had a translational component, indicating the uORF sequence was important for Arg-specific translational control. Comparisons with other uORFs suggest common elements in translational control mechanisms

  12. Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension

    Directory of Open Access Journals (Sweden)

    Entai Hou

    2017-05-01

    Full Text Available Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13BN rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO.

  13. Prevention of muscle fibers atrophy during gravitational unloading: The effect of L-arginine administration

    Science.gov (United States)

    Kartashkina, N.; Lomonosova, Y.; Shevchenko, T. F.; Bugrova, A. E.; Turtikova, O. V.; Kalamkarov, G. R.; Nemirovskaya, T. L.

    2011-05-01

    Gravitational unloading results in pronounced atrophy of m.soleus. Probably, the output of NO is controlled by the muscle activity. We hypothesized that NO may be involved in the protein metabolism and increase of its concentration in muscle can prevent atrophic changes induced by gravitational unloading. In order to test the hypothesis we applied NO donor L-arginine during gravitational unloading. 2.5-month-old male Wistar rats weighing 220-230g were divided into sedentary control group (CTR, n=7), 14-day hindlimb suspension (HS, n=7), 14 days of hindlimb suspension+ L-arginine (HSL, n=7) (with a daily supplementation of 500 mg/kg wt L-arginine) and 14 days of hindlimb suspension+ L-NAME (HSN, n=7) (90 mg/kg wt during 14 days). Cross sectional area (CSA) of slow twitch (ST) and fast twitch (FT) soleus muscle fibers decreased by 45% and 28% in the HS group ( pL-arginine administration. The levels of atrogin-1 mRNA were considerably altered in suspended animals (HS group: plus 27%, HSL group: minus 13%) as compared to the control level. Conclusion: L-arginine administration allows maintaining NO concentration in m.soleus at the level of cage control group, prevents from dystrophin layer destruction, decreases the atrogin mRNA concentration in the muscle and atrophy level under gravitational unloading.

  14. l-Arginine supplementation improves rats' antioxidant system and exercise performance.

    Science.gov (United States)

    Silva, E P; Borges, L S; Mendes-da-Silva, C; Hirabara, S M; Lambertucci, R H

    2017-03-01

    Reactive species have great importance in sports performance, once they can directly regulate energy production, muscular contraction, inflammation, and fatigue. Therefore, the redox control is essential for athletes' performance. Studies demonstrated that l-arginine has an important role in the synthesis of urea, cell growth and production of nitric oxide, moreover, there are indications that it is also able to induce benefits to muscle antioxidant system through the upregulation of some antioxidant enzymes, and by inhibiting some pathways of reactive species production. Therefore, the aim of this study was to evaluate the effects of l-arginine supplementation on performance and oxidative stress of male rats (trained or not), submitted to a single session of high intensity exercise. Forty male Wistar rats were divided into four groups, control (C), control+l-arginine (C + A), trained (T), and trained+l-arginine (T + A). The aerobic training was conducted for 8 weeks. Data of maximum speed and time from tests were used as indicators of performance. Variables related to oxidative stress and antioxidant system were also evaluated. Aerobic training was capable to induce enhancements on animals' exercise performance and on their redox state. Additionally, supplementation improved rats' physical performance on both groups, control and trained. Different improvements between groups on the antioxidant capacity were observed. Nevertheless, considering the ergogenic effect of l-arginine and the lack of all positive adaptations promoted by the exercise training, untrained animals may be more exposed to oxidative damages after the practice of intense exercises.

  15. L-Arginine Modulates Glucose and Lipid Metabolism in Obesity and Diabetes.

    Science.gov (United States)

    Hu, Shengdi; Han, Meng; Rezaei, Arash; Li, Defa; Wu, Guoyao; Ma, Xi

    2017-01-01

    Type 2 diabetes has become a global public health problem affecting approximately 380 million people throughout the world. It can cause many complications and lead to greater mortality. At present, there is no available medicine for effectively preventing diabetes. L-arginine, a functional amino acid, the precursor of nitric oxide, plays a crucial role in maintenance, reproduction, growth, anti-aging and immunity for animals. Growing clinical evidence indicates that dietary L-arginine supplementation can reduce obesity, decrease arterial blood pressure, resist oxidation and normalize endothelial dysfunction to bring about remission of type 2 diabetes. The potential molecular mechanism may play a role in modulating glucose homeostasis, promoting lipolysis, maintaining hormone levels, ameliorating insulin resistance, and fetal programing in early stages. The possible signaling pathway of the beneficial effects of L-arginine likely involves L-arginine-nitric oxide pathway through which cell signal protein can be activated. Accumulating studies have indicated that L-arginine may have potential to prevent and/or relieve type 2 diabetes via restoring insulin sensitivity in vivo. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension.

    Science.gov (United States)

    Hou, Entai; Sun, Na; Zhang, Fuchang; Zhao, Chenyang; Usa, Kristie; Liang, Mingyu; Tian, Zhongmin

    2017-05-23

    Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13 BN rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Mechanism of Allosteric Inhibition of N-Acetyl-L-glutamate Synthase by L-Arginine

    Energy Technology Data Exchange (ETDEWEB)

    Min, Li; Jin, Zhongmin; Caldovic, Ljubica; Morizono, Hiroki; Allewell, Norma M.; Tuchman, Mendel; Shi, Dashuang (GUW); (Maryland); (GWU); (Georgia)

    2010-01-07

    N-Acetylglutamate synthase (NAGS) catalyzes the first committed step in L-arginine biosynthesis in plants and micro-organisms and is subject to feedback inhibition by L-arginine. This study compares the crystal structures of NAGS from Neisseria gonorrhoeae (ngNAGS) in the inactive T-state with L-arginine bound and in the active R-state complexed with CoA and L-glutamate. Under all of the conditions examined, the enzyme consists of two stacked trimers. Each monomer has two domains: an amino acid kinase (AAK) domain with an AAK-like fold but lacking kinase activity and an N-acetyltransferase (NAT) domain homologous to other GCN5-related transferases. Binding of L-arginine to the AAK domain induces a global conformational change that increases the diameter of the hexamer by {approx}10 {angstrom} and decreases its height by {approx}20{angstrom}. AAK dimers move 5{angstrom} outward along their 2-fold axes, and their tilt relative to the plane of the hexamer decreases by {approx}4{sup o}. The NAT domains rotate {approx}109{sup o} relative to AAK domains enabling new interdomain interactions. Interactions between AAK and NAT domains on different subunits also change. Local motions of several loops at the L-arginine-binding site enable the protein to close around the bound ligand, whereas several loops at the NAT active site become disordered, markedly reducing enzymatic specific activity.

  18. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

    Science.gov (United States)

    Geiger, Roger; Rieckmann, Jan C; Wolf, Tobias; Basso, Camilla; Feng, Yuehan; Fuhrer, Tobias; Kogadeeva, Maria; Picotti, Paola; Meissner, Felix; Mann, Matthias; Zamboni, Nicola; Sallusto, Federica; Lanzavecchia, Antonio

    2016-10-20

    Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Relationship between serum arginase I and l-arginine or exhaled nitric oxide in asthma.

    Science.gov (United States)

    Ogino, Keiki; Obase, Yasushi; Ito, Tatsuo; Fujimura, Masaki; Eguchi, Eri; Kubo, Masayuki; Nagaoka, Kenjiro; Nakamura, Hiroyuki

    2016-01-01

    The relationship between serum arginase I and serum l-arginine or fractional exhaled nitric oxide (FENO) was evaluated cross-sectionally in asthmatic patients. No sex difference was observed in the serum mean levels of arginase I and l-arginine or FENO. Arginase I and FENO were higher in patients 60 or younger years than in those over 60 years. Asthmatic patients were divided into three groups: no steroid therapy, inhalation steroid therapy, and oral steroid therapy. Arginase I, FENO and high-sensitivity-C-reactive protein (hs-CRP) were significantly lower in the inhalation steroid therapy group than in the no steroid therapy group. Correlations were observed between arginase I and FENO, l-arginine, hs-CRP, WBC, and age, and also between FENO and IgE, WBC, and age. A logistic regression analysis revealed the positive association of arginase I with FENO, and the negative association of l-arginine. FENO was positively associated with arginase I and IgE. These results indicated that serum arginase I might influence serum levels of l-arginine and FENO, and that IgE might influence FENO in asthmatic patients.

  20. Hemodynamic and vascular response to resistance exercise with L-arginine.

    Science.gov (United States)

    Fahs, Christopher A; Heffernan, Kevin S; Fernhall, Bo

    2009-04-01

    L-arginine, the precursor to nitric oxide (NO), has been shown to improve endothelial function in patients with endothelial dysfunction. Resistance exercise has been shown to increase arterial stiffness acutely with no definitive cause. It is possible that a reduction in NO bioavailability is responsible for this. The purpose of this study was to examine the effect of acute L-arginine supplementation and resistance exercise on arterial function. Eighteen (N = 18) young men (24.2 +/- 0.7 yr) volunteered for this study. In a crossover design, subjects underwent body composition testing, 1-repetition maximum testing for the bench press and the biceps curls and performed two acute bouts of resistance exercise in which they consumed either placebo or 7 g L-arginine before each resistance exercise bout. Anthropometric measures, augmentation index (AIx), arterial stiffness, and forearm blood flow (FBF) were assessed before and after each treatment condition. There were significant (P L-arginine; furthermore, blood flow was not augmented with supplementation. On the basis of these data, l-arginine does not appear to change the hemodynamic and vascular responses to resistance exercise.

  1. L-Arginine as a potential ergogenic aid in healthy subjects.

    Science.gov (United States)

    Álvares, Thiago S; Meirelles, Cláudia M; Bhambhani, Yagesh N; Paschoalin, Vânia M F; Gomes, Paulo S C

    2011-03-01

    Dietary supplements containing L-arginine, a semi-essential amino acid, are one of the latest ergogenic aids intended to enhance strength, power and muscle recovery associated with both aerobic and resistance exercise. L-arginine is claimed to promote vasodilation by increasing nitric oxide (NO) production in the active muscle during exercise, improving strength, power and muscular recovery through increased substrate utilization and metabolite removal, such as lactate and ammonia. Research on L-arginine has recently tested this hypothesis, under the assumption that it may be the active compound associated with the vasodilator effects of NO. There were only five acute studies retrieved from the literature that evaluated exercise performance after L-arginine supplementation, three of which reported significant improvements. Regarding studies on chronic effects, eight studies were encountered: four reported enhancements in exercise performance, whilst four reports showed no changes. Whether these improvements in exercise performance - regardless of the aerobic or anaerobic nature of the exercise - can be associated with increases in NO production, has yet to be demonstrated in future studies. Low oral doses (≤20 g) are well tolerated and clinical side effects are rare in healthy subjects. In summary, it is still premature to recommend dietary supplements containing L-arginine as an ergogenic aid for healthy physically active subjects. © 2011 Adis Data Information BV. All rights reserved.

  2. Protective effects of arginine on fetal brain under maternal immobilization stress

    Directory of Open Access Journals (Sweden)

    E Enanat

    2015-10-01

    Full Text Available Background & aim: Arginine by regulating the biological activity of the brain plays an important role in reducing stress. Today's, stress is one of the century disease that created many problem.  This study conducted to determine the protective effect of arginine on nitric oxide levels in maternal fetal brain tissue under stress. Methods: Twenty pregnant Wistar rats (200-250 gr were randomly divided into four groups. With and without stress groups received arginine (200 mg/kg intraperitoneal from 5 – 20 days of pregnancies. Control with and sham without stress received 2 ml of normal saline. The pregnant rats were anesthetized by ketamine (100 mg/kg on the day 20 then the fetuses removed and weighed. Twenty five brain of fetal brain rat from each group were chosen for measuring of forebrain thickness and brain volume. Another 25 brain were chosen for measuring of nitric oxide. Data were analyzed by one way ANOVA. Results: Nitric oxide Levels reduced in stress rats treated with arginine compared to control group (P<0.05. The mean thickness of forebrain and hippicampal formation decreased in stress rats versus unstressed, but was not significant. The mean weight decreased significantly in stress group compared to the unstressed group (P<0.05. Conclusions: Arginine could protect the brain tissue and fetal weight by reducing the level of oxidative stress in the pregnant rats.

  3. Effects of l-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia1234

    Science.gov (United States)

    Bruins, Maaike J; Kessels, Fons; Luiking, Yvette C; Lamers, Wouter H; Deutz, Nicolaas EP

    2011-01-01

    Background: Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. Objective: The objective was to evaluate the effects of l-arginine pretreatment on arginine–nitric oxide (NO) production and hepatosplanchnic perfusion during subsequent endotoxemia. Design: In a randomized controlled trial, pigs (20–25 kg) received 3 μg ⋅ kg−1 ⋅ min−1 lipopolysaccharide (LPS; 5 endotoxin units/ng) intravenously and saline resuscitation. l-Arginine (n = 8; 5.3 μmol ⋅ kg−1 ⋅ min−1) or saline (n = 8) was infused starting 12 h before LPS infusion and continued for 24 h after the endotoxin infusion ended. Whole-body appearance rates, portal-drained viscera (PDV), and liver fluxes of arginine, citrulline, NO, and arginine de novo synthesis were measured by using stable-isotope infusion of [15N2]arginine and [13C-2H2]citrulline. Hepatosplanchnic perfusion was assessed by using a primed continuous infusion of para-aminohippuric acid and jejunal intramucosal partial pressure of carbon dioxide and was related to systemic hemodynamics. Results: Arginine supplementation before LPS increased whole-body NO production in the PDV but not in the liver. Furthermore, it increased blood flow in the portal vein but not in the aorta and hepatic artery. During endotoxin infusion, arginine pretreatment was associated with an increased whole-body arginine appearance and NO production in the gut. Additional effects included a preserved mean arterial pressure, the prevention of an increase in pulmonary arterial pressure, an attenuated metabolic acidosis, and an attenuated increase in the intramucosal partial pressure of carbon dioxide. Conclusion: Arginine treatment starting before endotoxemia appears to be beneficial because it improves hepatosplanchnic perfusion and oxygenation during prolonged endotoxemia, probably through an enhancement in NO synthesis, without causing deleterious systemic side effects. PMID

  4. Deletion of Genes Encoding Arginase Improves Use of "Heavy" Isotope-Labeled Arginine for Mass Spectrometry in Fission Yeast.

    Directory of Open Access Journals (Sweden)

    Weronika E Borek

    Full Text Available The use of "heavy" isotope-labeled arginine for stable isotope labeling by amino acids in cell culture (SILAC mass spectrometry in the fission yeast Schizosaccharomyces pombe is hindered by the fact that under normal conditions, arginine is extensively catabolized in vivo, resulting in the appearance of "heavy"-isotope label in several other amino acids, most notably proline, but also glutamate, glutamine and lysine. This "arginine conversion problem" significantly impairs quantification of mass spectra. Previously, we developed a method to prevent arginine conversion in fission yeast SILAC, based on deletion of genes involved in arginine catabolism. Here we show that although this method is indeed successful when (13C6-arginine (Arg-6 is used for labeling, it is less successful when (13C6(15N4-arginine (Arg-10, a theoretically preferable label, is used. In particular, we find that with this method, "heavy"-isotope label derived from Arg-10 is observed in amino acids other than arginine, indicating metabolic conversion of Arg-10. Arg-10 conversion, which severely complicates both MS and MS/MS analysis, is further confirmed by the presence of (13C5(15N2-arginine (Arg-7 in arginine-containing peptides from Arg-10-labeled cells. We describe how all of the problems associated with the use of Arg-10 can be overcome by a simple modification of our original method. We show that simultaneous deletion of the fission yeast arginase genes car1+ and aru1+ prevents virtually all of the arginine conversion that would otherwise result from the use of Arg-10. This solution should enable a wider use of heavy isotope-labeled amino acids in fission yeast SILAC.

  5. Effect of L-arginine on the growth ofPlasmodium falciparumand immune modulation of host cells.

    Science.gov (United States)

    Awasthi, Vikky; Chauhan, Rubika; Chattopadhyay, Debprasad; Das, Jyoti

    2017-01-01

    Malaria is a life-threatening disease caused by Plasmodium parasites. The life-cycle of Plasmodium species involves several stages both in mosquito and the vertebrate host. In the erythrocytic stage, Plasmodium resides inside the red blood cells (RBCs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required for growth and division of cells. The present study was aimed to demonstrate the effect of supplementation of different concentrations of L-arginine and L-citrulline on the growth of parasite, and effect of the culture supernatant on the host's peripheral blood mononuclear cells (PBMCs). To examine the effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in different concentrations of L-arginine, and L-citrulline supplemented in arginine deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation, the PBMCs isolated from healthy human host were cultured in the supernatant collected from P. falciparum culture. Growth of the parasite was greatly enhanced in L-arginine supplemented media and was found to be concentration dependent. However, parasite growth was compromised in L-citrulline supplemented and L-arginine deficient media. The supernatant collected from L-arginine supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL-10) expression as compared to the supernatant collected from L-citrulline supple- mented parasite media (sCit). The in vitro culture results showed, decreased parasite growth, and decreased expression of programmed cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline supplemented media as compared to L-arginine supplemented media. Hence, it was concluded that L-citrulline supplementation would be a better alternative than L-arginine to inhibit the parasite growth.

  6. Resolution and quantification of arginine, monomethylarginine, asymmetric dimethylarginine, and symmetric dimethylarginine in plasma using HPLC with internal calibration

    Science.gov (United States)

    Alkaitis, Matthew S.; Nardone, Glenn; Chertow, Jessica H.

    2015-01-01

    Abstract NG,NG‐dimethyl‐l‐arginine (asymmetric dimethylarginine, ADMA),NG‐monomethyl‐l‐arginine (l‐NMMA) and NG,N G’‐dimethyl‐l‐arginine (symmetric dimethylarginine, SDMA) are released during hydrolysis of proteins containing methylated arginine residues. ADMA and l‐NMMA inhibit nitric oxide synthase by competing with l‐arginine substrate. All three methylarginine derivatives also inhibit arginine transport. To enable investigation of methylarginines in diseases involving impaired nitric oxide synthesis, we developed a high‐performance liquid chromatography (HPLC) assay to simultaneously quantify arginine, ADMA, l‐NMMA and SDMA. Our assay requires 12 μL of plasma and is ideal for applications where sample availability is limited. We extracted arginine and methylarginines with mixed‐mode cation‐exchange columns, using synthetic monoethyl‐l‐arginine as an internal standard. Metabolites were derivatized with ortho‐phthaldialdeyhde and 3‐mercaptopropionic acid, separated by reverse‐phase HPLC and quantified with fluorescence detection. Standard curve linearity was ≥0.9995 for all metabolites. Inter‐day coefficient of variation (CV) values were ≤5% for arginine, ADMA and SDMA in human plasma and for arginine and ADMA in mouse plasma. The CV value for l‐NMMA was higher in human (10.4%) and mouse (15.8%) plasma because concentrations were substantially lower than ADMA and SDMA. This assay provides unique advantages of small sample volume requirements, excellent separation of target metabolites from contaminants and validation for both human and mouse plasma samples. © 2015 The Authors Biomedical Chromatography published by John Wiley & Sons, Ltd. PMID:26130049

  7. L-Arginine supplementation improves antioxidant defenses through L-arginine/nitric oxide pathways in exercised rats.

    Science.gov (United States)

    Shan, Lingling; Wang, Bin; Gao, Guizhen; Cao, Wengen; Zhang, Yunkun

    2013-10-15

    l-Arginine (l-Arg) supplementation has been shown to enhance physical exercise capacity and delay onset of fatigue. This work investigated the potential beneficial mechanism(s) of l-Arg supplementation by examining its effect on the cellular oxidative and nitrosative stress pathways in the exercised rats. Forty-eight rats were randomly divided into six groups: sedentary control; sedentary control with l-Arg treatment; endurance training (daily swimming training for 8 wk) control; endurance training with l-Arg treatment; an exhaustive exercise (one time swimming to fatigue) control; and an exhaustive exercise with l-Arg treatment. l-Arg (500 mg/kg body wt) or saline was given to rats by intragastric administration 1 h before the endurance training and the exhaustive swimming test. Expression levels and activities of the l-Arg/nitric oxide (NO) pathway components and parameters of the oxidative stress and antioxidant defense capacity were investigated in l-Arg-treated and control rats. The result show that the l-Arg supplementation completely reversed the exercise-induced activation of NO synthase and superoxide dismutase, increased l-Arg transport capacity, and increased NO and anti-superoxide anion levels. These data demonstrate that l-Arg supplementation effectively reduces the exercise-induced imbalance between oxidative stress and antioxidant defense capacity, and this modulation is likely mediated through the l-Arg/NO pathways. The findings of this study improved our understanding of how l-Arg supplementation prevents elevations of reactive oxygen species and favorably enhances the antioxidant defense capacity during physical exercise.

  8. Human urotensin II in internal mammary and radial arteries of patients undergoing coronary surgery

    DEFF Research Database (Denmark)

    Chen, Zhi-Wu; Yang, Qin; Huang, Yu

    2009-01-01

    (max):20.4+/-4.8%, p7.1%). The relaxation was abolished by endothelium denudation...... and by indomethacin, oxadiazoloquinoxalinone or N(omega)-nitro-L-arginine, oxyhemoglobin, and Ca2+-activated K+ channel (K(Ca)) blockers. Urotensin receptor mRNA was detected in both arteries. CONCLUSIONS: hU-II is an important spasmogen in arterial grafts with receptors expressed in IMA and RA. hU-II elicits...

  9. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease

    DEFF Research Database (Denmark)

    Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic...

  10. [Fosfomycin, lysine-fosfomycin, arginine-fosfomycin: antibacterial activity in vitro].

    Science.gov (United States)

    Angeretti, A; Martinetto, P; Valtz, A

    1980-01-01

    The antibacterial activity of NaFosfomicin and of two of its aminoacidic derivatives -Lisin-Fosfomycin and Arginin-Fosfomycin- has been determined "in vitro" as MICs and MBCs, on different groups of Bacteria. The results obtained were then statistically analyzed - according to the "t of Student" - in a comparative evaluation of the values between NaFosfomycin-Lisin-Fosfomycin (F-LF); NaFosfomycin-Arginin-Fosfomycin (F-AF); Lisin-Fosfomycin-Arginin-Fosfomycin (LF-AF). From these comparisons, the data found demonstrated no significant differences among the three compounds, for Proteus, Coliforms and Pseudomonas groups, while Salmonella and Staphylococcus Genera showed good differences (P less than 0.05) from the comparison F-AF.

  11. Buried lysine, but not arginine, titrates and alters transmembrane helix tilt.

    Science.gov (United States)

    Gleason, Nicholas J; Vostrikov, Vitaly V; Greathouse, Denise V; Koeppe, Roger E

    2013-01-29

    The ionization states of individual amino acid residues of membrane proteins are difficult to decipher or assign directly in the lipid-bilayer membrane environment. We address this issue for lysines and arginines in designed transmembrane helices. For lysines (but not arginines) at two locations within dioleoyl-phosphatidylcholine bilayer membranes, we measure pK(a) values below 7.0. We find that buried charged lysine, in fashion similar to arginine, will modulate helix orientation to maximize its own access to the aqueous interface or, if occluded by aromatic rings, may cause a transmembrane helix to exit the lipid bilayer. Interestingly, the influence of neutral lysine (vis-à-vis leucine) upon helix orientation also depends upon its aqueous access. Our results suggest that changes in the ionization states of particular residues will regulate membrane protein function and furthermore illustrate the subtle complexity of ionization behavior with respect to the detailed lipid and protein environment.

  12. Action of arginine for protection of ulcerative colitis by dextran sodium sulphate (DSS)

    International Nuclear Information System (INIS)

    Andrade, Maria Emilia Rabelo

    2016-01-01

    Recent studies have demonstrated the benefits of immunomodulators, such as arginine, in the regulation of inflammatory responses and trophism of the intestinal mucosa. The aim of this study was to evaluate the possible mechanisms action of arginine (pretreatment or treatment) in experimental model of ulcerative colitis induced by dextran sodium sulfate (DSS). C57BL/6 mice were randomized into 5 groups: Control group (C): standard diet and water; Arginine group (ARG): diet supplementation with arginine and water; Colitis group (COL): standard diet and DSS solution; Pretreated group (PT): diet supplementation with arginine before and during colitis induction; Treated group (T): diet supplementation with arginine during colitis induction. Colitis was induced by administration of 1.5% DSS for 5 days. After this, all the mice were euthanized and blood, organs and intestinal fluid were collected for carrying out analyzes. Parameters such as intestinal permeability (IP), bacterial translocation (BT), histological analysis (histological score, morphometric analysis, collagen and mucins stain), nitrate and nitrite, cytokines and chemokines, secretory immunoglobulin A (sIgA), inflammatory infiltrate and oxidative stress were performed. The ARG group did not show difference compared to group C in the investigated parameters (C vs ARG: p> 0.05). The COL group showed increased IP (C vs COL: p < 0.05) and BT (C vs COL: p <0.05). In the histological analysis, the COL group showed severe inflammation and reduction the crypts length. In addition, in the group COL observed increase infiltration of eosinophils, neutrophils and macrophages in the colon, increase cytokine IL-17 and chemokine KC in serum and oxidative stress in the colon (COL vs C: p <0.05). In the arginine-supplemented groups (PT and T) was observed decrease IP and BT to blood, liver and lung (PT and T vs Col: p <0.05). Histological analysis showed that the arginine (PT and T) preserved the intestinal mucosa and crypts

  13. Synthesis, thermal and nonlinear optical characterization of L-arginine semi-oxalate single crystals

    Science.gov (United States)

    Vasudevan, P.; Gokulraj, S.; Sankar, S.

    2012-06-01

    Optically good quality L-arginine semi-oxalate, an organic nonlinear optical crystal, has been synthesized from aqueous solution by slow evaporation method. Single crystal X-ray diffraction (XRD) analysis reveals that the synthesized L-arginine semi-oxalate crystal possesses triclinic structure with unit cell dimensions as a=5.05Å, b=9.73Å, c=13.12Å, α=111.030, β=92.790 and γ=91.910. The Fourier transform infra-red (FTIR) spectroscopy was analyzed and the presence of functional groups of L-arginine semi-oxalate was confirmed. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies show that the material is thermally stable up to 1460C and the melting point is 1500C. Kurtz and Perry powder technique confirms that the second harmonic generation (SHG) efficiency is 0.32 times that of standard organic materials urea and KDP.

  14. Competitive metabolism of L-arginine: arginase as a therapeutic target in asthma☆

    Science.gov (United States)

    Bratt, Jennifer M.; Zeki, Amir A.; Last, Jerold A.; Kenyon, Nicholas J.

    2011-01-01

    Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential toxicity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics. PMID:23554705

  15. Structural Basis for EarP-Mediated Arginine Glycosylation of Translation Elongation Factor EF-P

    Directory of Open Access Journals (Sweden)

    Ralph Krafczyk

    2017-09-01

    Full Text Available Glycosylation is a universal strategy to posttranslationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline-specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the crystal structure of EarP from Pseudomonas putida. The enzyme is composed of two opposing domains with Rossmann folds, thus constituting a B pattern-type glycosyltransferase (GT-B. While dTDP-β-l-rhamnose is located within a highly conserved pocket of the C-domain, EarP recognizes the KOW-like N-domain of EF-P. Based on our data, we propose a structural model for arginine glycosylation by EarP. As EarP is essential for pathogenicity in P. aeruginosa, our study provides the basis for targeted inhibitor design.

  16. Comparison of Arginine Hydrochloride and Acetazolamide for the Correction of Metabolic Alkalosis in Pediatric Patients.

    Science.gov (United States)

    Heble, Daniel E; Oschman, Alexandra; Sandritter, Tracy L

    Metabolic alkalosis is a common acid-base disturbance occurring in critically ill pediatric patients. Acetazolamide and arginine hydrochloride are pharmacologic agents used at our institution for patients refractory to first-line therapy or those unable to tolerate fluid replacement. The objective of this retrospective review was to determine if a course of arginine hydrochloride or acetazolamide was more effective at correcting metabolic alkalosis within a 24-hour period. Patients included received a course of acetazolamide or arginine hydrochloride for metabolic alkalosis with a repeat metabolic panel 18-30 hours after treatment initiation. Exclusion criteria consisted of previous treatment with either drug within 24 hours or a documented metabolic disorder. Efficacy was determined by proportion of patients achieving resolution of metabolic alkalosis (treatment success: serum CO2 96 mmol/L). Additionally, mean change in serum bicarbonate and chloride concentrations was assessed. Thirty-four patients met inclusion criteria, 19 patients received acetazolamide and 15 patients received arginine hydrochloride. Treatment success was similar in patients receiving acetazolamide and arginine hydrochloride (37% vs. 7%, P = 0.053). Correction of serum bicarbonate was observed in more patients treated with acetazolamide (42% vs. 7%, P = 0.047). Both groups had a similar increase in mean serum chloride concentration (5.7 ± 5.3 vs. 4.4 ± 4.4 mmol/L, P = 0.458). Mean decrease in serum bicarbonate concentration was equivalent between groups (5.6 ± 5.2 vs. 2.8 ± 4.7, mmol/L, P = 0.110). Acetazolamide and arginine hydrochloride appear to be equally effective in correcting metabolic alkalosis in critically ill pediatric patients.

  17. Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49.

    Science.gov (United States)

    Hering, Silvio; Sieg, Antje; Kreikemeyer, Bernd; Fiedler, Tomas

    2013-09-01

    Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen causing mild superficial infections of skin and mucous membranes, but also life-threatening systemic diseases. S. pyogenes and other prokaryotic organisms use the arginine deiminase system (ADS) for survival in acidic environments. In this study, the arginine deiminase (AD), and carbamate kinase (CK) from S. pyogenes M49 strain 591 were heterologously expressed in Escherichia coli DH5α, purified, and kinetically characterized. AD and CK from S. pyogenes M49 share high amino acid sequence similarity with the respective enzymes from Lactococcus lactis subsp. lactis IL1403 (45.6% and 53.5% identical amino acids) and Enterococcus faecalis V583 (66.8% and 66.8% identical amino acids). We found that the arginine deiminase of S. pyogenes is not allosterically regulated by the intermediates and products of the arginine degradation (e.g., ATP, citrulline, carbamoyl phosphate). The Km and Vmax values for arginine were 1.13±0.12mM (mean±SD) and 1.51±0.07μmol/min/mg protein. The carbamate kinase is inhibited by ATP but unaffected by arginine and citrulline. The Km and Vmax values for ADP were 0.72±0.08mM and 1.10±0.10μmol/min/mg protein and the Km for carbamoyl phosphate was 0.65±0.07mM. The optimum pH and temperature for both enzymes were 6.5 and 37°C, respectively. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Supplementation with rumen-protected L-arginine-HCl increased fertility in sheep with synchronized estrus.

    Science.gov (United States)

    de Chávez, Julio Agustín Ruiz; Guzmán, Adrian; Zamora-Gutiérrez, Diana; Mendoza, Germán David; Melgoza, Luz María; Montes, Sergio; Rosales-Torres, Ana María

    2015-08-01

    The aim of the present study was to evaluate the effects of L-arginine-HCl supplementation on ovulation rate, fertility, prolificacy, and serum VEGF concentrations in ewes with synchronized oestrus. Thirty Suffolk ewes with a mean body weight of 45 ± 3 kg and a mean body condition score (BCS) of 2.4 ± 0.28 were synchronized for estrus presentation with a progestin-containing sponge (20 mg Chronogest® CR) for 9 days plus PGF2-α (Lutalyse; Pfizer, USA) on day 7 after the insertion of the sponge. The ewes were divided into two groups; i.e., a control group (n = 15) that was fed on the native pasture (basal diet) and an L-arginine-HCl group (n = 15) that received 7.8 g of rumen-protected L-arginine-HCl from day 5 of the sponge insertion until day 25 after mating plus the basal diet. The L-arginine-HCl was administered daily via an esophageal probe between days 5 and 9 of the synchronization protocol and every third day subsequently. Blood samples were drawn from the jugular vein every 6 days throughout the entire experimental period. The results revealed that the L-arginine-HCl supplementation increased fertility during the synchronized estrus (P = 0.05). However, no effects were observed on the final BCS (P = 0.78), estrus presentation (P = 0.33), multiple ovulations (P = 0.24), prolificacy (P = 0.63), or serum VEGF concentration. In conclusion, L-arginine-HCl supplementation during the period used in this study increased fertility in sheep with synchronized estrus possibly due to improved embryo-fetal survival during early pregnancy.

  19. Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

    International Nuclear Information System (INIS)

    Cheng Wei; Oike, Masahiro; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

    2005-01-01

    The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca 2+ transients and cellular uptake of L-[ 3 H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[ 3 H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine

  20. Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep.

    Science.gov (United States)

    Carey Satterfield, M; Dunlap, Kathrin A; Keisler, Duane H; Bazer, Fuller W; Wu, Guoyao

    2012-10-01

    The global incidence of human obesity has more than doubled over the past three decades. An ovine model of obesity was developed to determine effects of maternal obesity and arginine supplementation on maternal, placental, and fetal parameters of growth, health, and well being. One-hundred-twenty days prior to embryo transfer, ewes were fed either ad libitum (n = 10) to induce obesity or 100% National Research Council-recommended nutrient requirements (n = 10) as controls. Embryos from superovulated ewes with normal body condition were transferred to the uterus of control-fed and obese ewes on day 5.5 post-estrus to generate genetically similar singleton pregnancies. Beginning on day 100 of gestation, obese ewes received intravenous administration of saline or L-arginine-HCl three times daily (81 mg arginine/kg body weight/day) to day 125, whereas control-fed ewes received saline. Fetal growth was assessed at necropsy on day 125. Maternal obesity increased (1) percentages of maternal and fetal carcass lipids and (2) concentrations of leptin, insulin, glucose, glutamate, leucine, lysine and threonine in maternal plasma while reducing (1) concentrations of progesterone, glycine and serine in maternal plasma and (2) amniotic and allantoic fluid volumes. Administration of L-arginine to obese ewes increased arginine and ornithine concentrations in maternal and fetal plasma, amniotic fluid volume, protein content in maternal carcass, and fetal brown adipose tissue (+60%), while reducing maternal lipid content and circulating leptin levels. Fetal or placental weight did not differ among treatments. Results indicate that arginine treatment beneficially reduces maternal adiposity and enhances fetal brown adipose tissue development in obese ewes.

  1. Regulation of autophagy by systemic admission of microRNA-141 to target HMGB1 in l-arginine-induced acute pancreatitis in vivo.

    Science.gov (United States)

    Zhu, Hongwei; Huang, Lihua; Zhu, Shaihong; Li, Xia; Li, Zhiqiang; Yu, Can; Yu, Xiao

    2016-01-01

    MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate gene expression by binding to the 3' untranslated region (UTR) of target mRNAs and can be applied in gene therapy. Acute pancreatitis is an inflammatory pancreatic disease that carries considerable morbidity and mortality. The purpose of this study was to explore the therapeutic potential of microRNA-141 (miR-141) for acute pancreatitis in vivo. AP was induced by two hourly intra-peritoneal (i.p.) injections of l-arginine (200mg × 2/100 g.BW). Control mice received normal saline injections. In a separate group, normal saline, empty adenoviral vector and miR-141 adenoviral vector were given to the mice via tail vein hydrodynamically at 72 h before the first l-arginine injection. All the mice were euthanized at 24 h after the last l-arginine injection, and the pancreatic tissues were assessed by qRT-PCR, Western blotting and electron microscopy. miR-141 directly inhibited HMGB1 expression in mouse hepal-6 cell. Furthermore, systemic administration of the miR-141 knock-down the expression of HMGB1 protein and further antagonized the downstream protein Beclin-1, leading to the reduction of autophagosomes and autolysosomes, blockade of the LC3-II level and the increased levels of p62 protein after injection of l-arginine. In addition, the level of Lamp-2 was not significantly different. For the first time miR-141 was applied in acute pancreatitis treatment in vivo. Inhibition of HMGB1 by miR-141 may block the process of autophagosome formation through the HMGB1/Beclin-1 pathway. The miR-141 appears to be a promising candidate for the gene therapy of acute pancreatitis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

    Directory of Open Access Journals (Sweden)

    C.H. Santuzzi

    2015-01-01

    Full Text Available Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK and L-arginine treatment both alone and in combination on blood pressure (BP, and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C hypertension, 2K1C+ALSK (ALSK, 2K1C+L-arginine (L-arg, and 2K1C+ALSK+L-arginine (ALSK+L-arg treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

  3. NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice

    NARCIS (Netherlands)

    Luiking, Yvette C.; Hallemeesch, Marcella M.; Lamers, Wouter H.; Deutz, Nicolaas E. P.

    2005-01-01

    Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino

  4. L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

    Science.gov (United States)

    L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at th...

  5. Heritability and genetic variance for citrulline, arginine and lycopene content in a diverse set of watermelon cultigens

    Science.gov (United States)

    Citrulline, arginine, and lycopene are naturally occurring compounds found in watermelon, Citrullus lanatus (Thumb) Matsum & Nakai, with beneficial effects on plant growth and human health. This study evaluated seven commercial cultivars and one breeding line for citrulline, arginine, and lycopene c...

  6. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  7. Diminished citrulline-arginine-nitric oxide production rates are associated with necrotizing enterocolitis incidence in premature pigs

    Science.gov (United States)

    Necrotizing enterocolitis (NEC) is a major gastrointestinal disease in premature infants that is associated with formula feeding and intestinal hypoxia. Low arginine availability in these infants has been linked to NEC since arginine is the sole precursor of nitric oxide (NO), a critical mediator of...

  8. L-arginine supplementation in hyperdynamic endotoxemic pigs: effect on nitric oxide synthesis by the different organs

    NARCIS (Netherlands)

    Bruins, Maaike J.; Soeters, Peter B.; Lamers, Wouter H.; Meijer, Alfred J.; Deutz, Nicolaas E. P.

    2002-01-01

    OBJECTIVES: Under septic conditions, the protective role of nitric oxide in the organs may become compromised at a time of increased demand as a result of decreased availability of L-arginine. It remains unknown whether supplementation with L-arginine, as a substrate, can modulate organ nitric oxide

  9. Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs1-3

    NARCIS (Netherlands)

    P.J. Puiman (Patrycja); B. Stoll (Barbara); J.B. van Goudoever (Hans); D.G. Burrin (Douglas)

    2011-01-01

    textabstractArginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemiareperfusion models and low plasma levels are

  10. L-arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia

    NARCIS (Netherlands)

    Bruins, Maaike J.; Soeters, Peter B.; Lamers, Wouter H.; Deutz, Nicolaas E. P.

    2002-01-01

    BACKGROUND: Accumulating evidence suggests that L-arginine, under conditions of septicemia, not only enhances immune function but also improves protein metabolism. OBJECTIVE: Because the effect of L-arginine administration on the protein metabolism of different organs is unknown, the aim of the

  11. Dietary L-arginine supplementation during mouse gestation enhances reproductive performance and Vegfr2 transcription activity in the fetoplacental unit

    Science.gov (United States)

    Regarded as one of the most versatile amino acids, arginine serves as a precursor for many molecules and has been reported to improve the reproductive performance of rats and pigs. To this end, we sought to determine if dietary L-arginine alters fetoplacental vascular endothelial growth factor recep...

  12. High-performance liquid chromatography method with radiochemical detection for measurement of nitric oxide synthase, arginase, and arginine decarboxylase activities

    DEFF Research Database (Denmark)

    Volke, A; Wegener, Gregers; Vasar, E

    2006-01-01

    Nitric oxide has been shown to be involved in numerous biological processes, and many studies have aimed to measure nitric oxide synthase (NOS) activity. Recently, it has been demonstrated that arginase and arginine decarboxylase (ADC), two enzymes that also employ arginine as a substrate, may re...

  13. Reconstitution of T Cell Proliferation under Arginine Limitation: Activated Human T Cells Take Up Citrulline via L-Type Amino Acid Transporter 1 and Use It to Regenerate Arginine after Induction of Argininosuccinate Synthase Expression

    Directory of Open Access Journals (Sweden)

    Anke Werner

    2017-07-01

    Full Text Available In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological antitumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate (ASA in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS and argininosuccinate lyase (ASL. Here, we demonstrate that anti-CD3/anti-CD28-activated human primary CD4+ and CD8+ T cells upregulate ASS expression in response to low extracellular arginine concentrations, while ASL is expressed constitutively. ASS expression peaked under moderate arginine restriction (20 µM, but no relevant induction was detectable in the complete absence of extracellular arginine. The upregulated ASS correlated with a reconstitution of T cell proliferation upon supplementation of citrulline, while the suppressed production of IFN-γ was refractory to citrulline substitution. In contrast, ASA reconstituted proliferation and cytokine synthesis even in the complete absence of arginine. By direct quantification of intracellular metabolites we show that activated primary human T cells import citrulline but only metabolize it further to ASA and arginine when ASS is expressed in the context of low amounts of extracellular arginine. We then clarify that citrulline transport is largely mediated by the L-type amino acid transporter 1 (LAT1, induced upon human T cell activation. Upon siRNA-mediated knockdown of LAT1, activated T cells lost the ability to import citrulline. These data underline the potential of citrulline substitution as a promising pharmacological way to treat immunosuppression in settings of arginine deprivation.

  14. L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis.

    Directory of Open Access Journals (Sweden)

    Juliana Ide Aoki

    2017-10-01

    Full Text Available Leishmania uses the amino acid L-arginine as a substrate for arginase, enzyme that produces urea and ornithine, last precursor of polyamine pathway. This pathway is used by the parasite to replicate and it is essential to establish the infection in the mammalian host. L-arginine is not synthesized by the parasite, so its uptake occurs through the amino acid permease 3 (AAP3. AAP3 is codified by two copies genes (5.1 and 4.7 copies, organized in tandem in the parasite genome. One copy presents the expression regulated by L-arginine availability.RNA-seq data revealed 14 amino acid transporters differentially expressed in the comparison of La-WT vs. La-arg- promastigotes and axenic amastigotes. The 5.1 and 4.7 aap3 transcripts were down-regulated in La-WT promastigotes vs. axenic amastigotes, and in La-WT vs. La-arg- promastigotes. In contrast, transcripts of other transporters were up-regulated in the same comparisons. The amount of 5.1 and 4.7 aap3 mRNA of intracellular amastigotes was also determined in sample preparations from macrophages, obtained from BALB/c and C57BL/6 mice and the human THP-1 lineage infected with La-WT or La-arg-, revealing that the genetic host background is also important. We also determined the aap3 mRNA and AAP3 protein amounts of promastigotes and axenic amastigotes in different environmental growth conditions, varying pH, temperature and L-arginine availability. Interestingly, the increase of temperature increased the AAP3 level in plasma membrane and consequently the L-arginine uptake, independently of pH and L-arginine availability. In addition, we demonstrated that besides the plasma membrane localization, AAP3 was also localized in the glycosome of L. amazonensis promastigotes and axenic amastigotes.In this report, we described the differential transcriptional profiling of amino acids transporters from La-WT and La-arg- promastigotes and axenic amastigotes. We also showed the increased AAP3 levels under amino

  15. Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats

    OpenAIRE

    Moura,José Ricardo Sousa Ayres de; Sass,Nelson; Guimarães,Sérgio Botelho; Vasconcelos,Paulo Roberto Leitão de; Mattar,Rosiane; Kulay Jr,Luis

    2006-01-01

    PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR). METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1). Pregnancy was confirmed by sperm-positive vaginal smear (Day 0). Wistar-EPM-1 rats served as counterpart control (C-1). SHR rats were randomized in 4 groups (n=10): Group Control 2, non-treated rats; Group L-Arginine...

  16. L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis.

    Science.gov (United States)

    Aoki, Juliana Ide; Muxel, Sandra Marcia; Zampieri, Ricardo Andrade; Acuña, Stephanie Maia; Fernandes, Juliane Cristina Ribeiro; Vanderlinde, Rubia Heloisa; Sales, Maria Carmen Oliveira de Pinho; Floeter-Winter, Lucile Maria

    2017-10-01

    Leishmania uses the amino acid L-arginine as a substrate for arginase, enzyme that produces urea and ornithine, last precursor of polyamine pathway. This pathway is used by the parasite to replicate and it is essential to establish the infection in the mammalian host. L-arginine is not synthesized by the parasite, so its uptake occurs through the amino acid permease 3 (AAP3). AAP3 is codified by two copies genes (5.1 and 4.7 copies), organized in tandem in the parasite genome. One copy presents the expression regulated by L-arginine availability. RNA-seq data revealed 14 amino acid transporters differentially expressed in the comparison of La-WT vs. La-arg- promastigotes and axenic amastigotes. The 5.1 and 4.7 aap3 transcripts were down-regulated in La-WT promastigotes vs. axenic amastigotes, and in La-WT vs. La-arg- promastigotes. In contrast, transcripts of other transporters were up-regulated in the same comparisons. The amount of 5.1 and 4.7 aap3 mRNA of intracellular amastigotes was also determined in sample preparations from macrophages, obtained from BALB/c and C57BL/6 mice and the human THP-1 lineage infected with La-WT or La-arg-, revealing that the genetic host background is also important. We also determined the aap3 mRNA and AAP3 protein amounts of promastigotes and axenic amastigotes in different environmental growth conditions, varying pH, temperature and L-arginine availability. Interestingly, the increase of temperature increased the AAP3 level in plasma membrane and consequently the L-arginine uptake, independently of pH and L-arginine availability. In addition, we demonstrated that besides the plasma membrane localization, AAP3 was also localized in the glycosome of L. amazonensis promastigotes and axenic amastigotes. In this report, we described the differential transcriptional profiling of amino acids transporters from La-WT and La-arg- promastigotes and axenic amastigotes. We also showed the increased AAP3 levels under amino acid starvation or

  17. Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.

    Science.gov (United States)

    Kim, Kiyoung; Hurr, Chansol; Patik, Jordan C; Matthew Brothers, R

    2018-02-03

    It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer's solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2‑boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 μl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ± 12 vs. AA: 62 ± 6 vs. %CVCmax; P l-arginine site (Control: 62 ± 6 vs. l-arginine: 70 ± 18%CVCmax; P l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA. Copyright © 2018. Published by Elsevier Inc.

  18. Polarized Raman spectra of L-arginine hydrochloride monohydrated single crystal

    Energy Technology Data Exchange (ETDEWEB)

    Faria, J.L.B. [Universidade Federal de Mato Grosso (UFMT), Cuiaba, MT (Brazil). Dept. de Fisica; Freire, P.T.C.; Goncalves, R.O.; Melo, F.E.A.; Mendes Filho, J., E-mail: tarso@fisica.ufc.b [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Fisica; Lima, R.J.C.; Moreno, A.J.D. [Universidade Federal do Maranhao (UFMA), Imperatriz, MA (Brazil). Centro de Ciencias Sociais, Saude e Tecnologia

    2010-09-15

    Polarized Raman spectra of L-arginine hydrochloride monohydrated single crystal in nine different scattering geometries of the two irreducible representations of factor group C{sub 2} were studied at room temperature. The experimental wavenumber values are compared with those obtained from ab-initio calculation and the assignment of the Raman bands to the respective molecular vibrations is also given. Finally, a discussion related to a previously reported phase transition undergone by L-arginine hydrochloride monohydrated single crystal at low temperature is furnished. (author)

  19. Effects of oral supplementation of L-arginine in the treatment of pulmonary hypertension secondary to pulmonary embolism: a case report

    OpenAIRE

    Ogata, Hiroshi; Takahashi, Tomoko; Ishikawa, Kazunobu; Ishibashi, Tosiyuki; Maruyama, Yukio; Watanabe, Machiko; Edo, Kiyoto

    2010-01-01

    We tried L-arginine for the treatment of pulmonary hypertension secondary to pulmonary embolism. The plasma brain natriuretic peptide (BNP) level inversely correlated with the plasma concentration of L-arginine. After oral supplementation of L-arginine, patient's symptoms (shortness of breath and general malaise), state of congestive heart failure, and exercise capacity all improved. L-arginine may be effective in the treatment of pulmonary hypertension secondary to pulmonary embolism.

  20. Effects of chronic oral L-arginine administration on the L-arginine/NO pathway in patients with peripheral arterial occlusive disease or coronary artery disease: L-Arginine prevents renal loss of nitrite, the major NO reservoir.

    Science.gov (United States)

    Schneider, Jessica Y; Rothmann, Sabine; Schröder, Frank; Langen, Jennifer; Lücke, Thomas; Mariotti, François; Huneau, Jean François; Frölich, Jürgen C; Tsikas, Dimitrios

    2015-09-01

    Despite saturation of nitric oxide (NO) synthase (NOS) by its substrate L-arginine (Arg), oral and intravenous supplementation of Arg may enhance NO synthesis, a phenomenon known as "The L-arginine paradox". Yet, Arg is not only a source of NO, but is also a source for guanidine-methylated (N (G)) arginine derivatives which are all inhibitors of NOS activity. Therefore, Arg supplementation may not always result in enhanced NO synthesis. Concomitant synthesis of N (G)-monomethyl arginine (MMA), N (G),N (G)-dimethylarginine (asymmetric dimethylarginine, ADMA) and N (G),N (G´)-dimethylarginine (symmetric dimethylarginine, SDMA) from supplemented Arg may outweigh and even outbalance the positive effects of Arg on NO. Another possible, yet little investigated effect of Arg supplementation may be alteration of renal function, notably the influence on the excretion of nitrite in the urine. Nitrite is the autoxidation product of NO and the major reservoir of NO in the circulation. Nitrite and Arg are reabsorbed in the proximal tubule of the nephron and this reabsorption is coupled, at least in part, to the renal carbonic anhydrase (CA) activity. In the present placebo-controlled studies, we investigated the effect of chronic oral Arg supplementation of 10 g/day for 3 or 6 months in patients suffering from peripheral arterial occlusive disease (PAOD) or coronary artery disease (CAD) on the urinary excretion of nitrite relative to nitrate. We determined the urinary nitrate-to-nitrite molar ratio (UNOxR), which is a measure of nitrite-dependent renal CA activity before and after oral intake of Arg or placebo by the patients. The UNOxR was also determined in 6 children who underwent the Arg test, i.e., intravenous infusion of Arg (0.5 g Arg/kg bodyweight) for 30 min. Arg was well tolerated by the patients of the three studies. Oral Arg supplementation increased Arg (plasma and urine) and ADMA (urine) concentrations. No appreciable changes were seen in NO (in PAOD and CAD) and

  1. Supplementation of bovine embryo culture medium with L-arginine improves embryo quality via nitric oxide production.

    Science.gov (United States)

    Santana, Priscila Di Paula Bessa; Silva, Thiago Velasco Guimarães; da Costa, Nathália Nogueira; da Silva, Bruno Barauna; Carter, Timothy Frederick; Cordeiro, Marcela da Silva; da Silva, Bruno José Martins; Santos, Simone do Socorro Damasceno; Herculano, Anderson Manoel; Adona, Paulo Roberto; Ohashi, Otávio Mitio; Miranda, Moysés dos Santos

    2014-10-01

    Nitric oxide (NO) is a cell-signaling molecule that regulates a variety of molecular pathways. We investigated the role of NO during preimplantation embryonic development by blocking its production with an inhibitor or supplementing in vitro bovine embryo cultures with its natural precursor, L-arginine, over different periods. Endpoints evaluated included blastocyst rates, development kinetics, and embryo quality. Supplementation with the NO synthase inhibitor N-Nitro-L-arginine-methyl ester (L-NAME) from Days 1 to 8 of culture decreased blastocyst (P L-arginine decreased blastocyst rates (P L-arginine improved embryo hatching rates (P supplementing the embryo culture medium with L-arginine favors preimplantation development of bovine embryos. © 2014 Wiley Periodicals, Inc.

  2. Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: A double-blind, randomized, clinical trial.

    Science.gov (United States)

    Camarena Pulido, E E; García Benavides, L; Panduro Barón, J G; Pascoe Gonzalez, S; Madrigal Saray, A J; García Padilla, F E; Totsuka Sutto, S E

    2016-05-01

    This study aimed to estimate the effectiveness of L-arginine for preventing preeclampsia in high-risk pregnancy. We performed a randomized, double-blind, placebo-controlled, clinical trial in patients with high-risk factors for preeclampsia. Fifty subjects received L-arginine, beginning from the 20th week of gestation. An additional 50 patients received homologated placebo. The placebo group had a higher number of cases of preeclampsia (11/47) compared with the L-arginine group (3/49, P = 0.01). Birth weight was higher in the L-arginine group and there was a smaller number of preterm births (P = 0.03). L-arginine is effective for preventing preeclampsia.

  3. The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

    Directory of Open Access Journals (Sweden)

    Ruijter Jan M

    2008-11-01

    Full Text Available Abstract Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS, ornithine aminotransferase (OAT, argininosuccinate synthetase (ASS, arginase-1 (ARG1, arginase-2 (ARG2, and nitric-oxide synthase (NOS were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Results Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. Conclusion The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.

  4. Role of the L-citrulline/L-arginine cycle in iNANC nerve-mediated nitric oxide production and airway smooth muscle relaxation in allergic asthma

    NARCIS (Netherlands)

    Maarsingh, Ham; Leusink, John; Zaagsma, Johan; Meurs, Herman

    2006-01-01

    Nitric oxide synthase (NOS) converts L-arginine into nitric oxide (NO) and L-Citrulline. In NO-producing cells, L-citrulline can be recycled to L-arginine in a two-step reaction involving argininosuccinate synthase (ASS) and -lyase (ASL). In guinea pig trachea, L-arginine is a limiting factor in

  5. The Effects of Pretreatment with Various Doses of L-Arginine on Cisplatin-Induced Nephropathy of Male Rats

    Directory of Open Access Journals (Sweden)

    B Rasoulian

    2016-09-01

    Full Text Available Introduction: Cisplatin is a widely used anti-cancer drug, which its application is limited by nephrotoxicity. In this study, the effect of pretreatment with different l-arginine doses on Cisplatin-induced renal functional injury was investigated. Methods: 63 male rats were divided into 7 groups: In groups 3, 4, 5 and 6, 60 min before the Cisplatin injection (5mg/kg; L-Arginine with doses of 50,100,200 or 400mg/kg was injected, respectively. In group7, normal saline was injected before Cisplatin administration. In groups 1 and 2, normal saline was injected instead of Cisplatin. In group 2, 60min before normal saline injection, 400mg/kg L-Arginine was administered and in group1, instead of L-arginine, normal saline was injected too. Injections were intraperitoneal. 72h after Cisplatin injection, blood sampling and plasma separation were done. Urine sample was collected 24 hours before blood sampling by metabolic cage. The mean of plasma urea and creatinine levels and creatinine clearance (ml/day.kg and fractional excretion of Na (FENa, % were compared among different groups as renal functional parameters. Results: In comparison to group 7, L-arginine injection in a dose of 400mg/kg led to significant amelioration of all parameters. 200 mg/kg L-arginine administration led to significant decrease in plasma urea level and FENa. 100mg/kg L-arginine caused significant improvement in fractional excretion of sodium. L-arginine injection with 50mg/kg dose, significantly ameliorate all renal function tests instead of creatinine clearance. Conclusion: Pretreatment with L-arginine administration with 400 or 50 mg/kg doses, respectively, had the highest effect on reducing Cisplatin-induced nephropathy. L-arginine injection with intermediate doses i.e. 200 or 100 mg/kg had less effect in reducing Cisplatin-induced nephropathy and it needs more investigations.

  6. Protein Arginine Methyltransferase 5 as a Driver of Lymphomagenesis

    Science.gov (United States)

    Smith, Porsha Latrice

    Over the past decade, it has become clear that oncogenesis is a process driven by a wide variety of triggers including gene mutations, gene amplifications, inflammation, and immune deficiency. The growing pool of data collected from whole genome and epigenome studies of both solid and blood cancers has pointed toward dysregulation of chromatin remodelers as a unique class of cancer drivers. Next generation sequencing studies of lymphomas have identified a wide array of somatic mutations affecting enzymes that regulate epigenetic control of gene expression. Lymphoma is a type of cancer that originates in secondary lymphoid organs and manifests as an outgrowth of transformed lymphocytes, or white blood cells (WBCs) in the blood. The majority of lymphoma cases can be grouped into the Non-Hodgkins lymphoma (NHL) subset and mainly occurs in B-cells. B-cell NHL is a heterogeneous set of cancers that would benefit from new therapies to improve patient progression-free survival. Cancers such as NHL typically present with a combination of genetic and epigenetic aberrations that contribute to the malignancy program. The epigenetic modifier protein arginine methyltransferase 5 (PRMT5) is required for B-cell transformation following Epstein-Barr virus (EBV) infection, and is overexpressed in various subsets of B-cell NHL. Based on these data we hypothesized that PRMT5 is a major driver of B-cell lymphomagenesis. To explore the role of PRMT5 in the development and progression of B-cell NHL we created a small molecule inhibitors targeted to PRMT5. Using the NHL subset mantle cell lymphoma (MCL) as a model we tested the efficacy of the drug. We discovered that PRMT5 was overexpressed in MCL primary samples and cell lines as compared to normal resting B cells. Furthermore, use of the small molecule inhibitor decreased the proliferation and viability in these cells without affecting the normal B-cells. Additionally, use of inhibitors caused G2/M cell cycle and decreased the

  7. l-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms.

    Science.gov (United States)

    He, Jinzhi; Hwang, Geelsu; Liu, Yuan; Gao, Lizeng; Kilpatrick-Liverman, LaTonya; Santarpia, Peter; Zhou, Xuedong; Koo, Hyun

    2016-10-01

    l-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous l-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, l-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous l-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) l-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical l-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, l-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H2O2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H2O2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of l-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor. Dental caries is one

  8. Conductometric and volumetric studies of atorvastatin in aqueous solution of arginine from 298.15 to 313.15 K

    Directory of Open Access Journals (Sweden)

    M. M. R. Meor Mohd Affandi

    2016-01-01

    Full Text Available Categorized as a Biopharmaceutics Classification System Class II drugs, atorvastatin (ATV exhibits low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers. Numerous studies are available in regard to the solubility enhancement of ATV, but very few actually describe this phenomenon in terms of thermodynamics and the solute-solvent interaction. Arginine (ARG is an amino acid that has been reported to enhance the solubility of the highly insoluble wheat protein gluten through hydrogen bonding and π electron-cation interaction. To our knowledge, ARG has never been investigated as a solubility enhancement agent of aqueous insoluble drugs. Thus, this study aimed to elucidate the solute-solvent and solute-cosolute interactions and derive thermodynamic parameters that bolstered the solubility of ATV in the presence of ARG. We examined the electrolytic conductance and densities of ATV-ARG binary system covering the temperature ranging from 298.15 K to 313.15 K. Conductometric and volumetric parameters such as limiting molar conductance, association constants, limiting partial molar volumes, and expansibility values were calculated. Additionally, thermodynamic parameters (ΔG0, ΔH0, ΔS0, and Es involved in the association process of the solute in the aqueous solution of ARG were also determined.

  9. Aliskiren and l-arginine treatments restore depressed baroreflex sensitivity and decrease oxidative stress in renovascular hypertension rats.

    Science.gov (United States)

    Mengal, Vinicius; Silva, Paulo Hm; Tiradentes, Renata V; Santuzzi, Cintia H; de Almeida, Simone A; Sena, Gabriela C; Bissoli, Nazare S; Abreu, Glaucia R; Gouvea, Sonia A

    2016-11-01

    Renovascular hypertension is characterized by increased angiotensin II and oxidative stress, and by endothelial dysfunction. The purpose of this study was to test whether the administration of aliskiren (ALSK) and l-arginine (l-ARG) would restore impaired baroreflex sensitivity and reduce oxidative stress in a rat renovascular hypertension model. Hypertension was induced by clipping the left renal artery, and the following five groups were created: SHAM; two-kidney, 1-clip (2K1C); 2K1C plus ALSK (ALSK); 2K1C plus l-ARG (l-ARG); and 2K1C plus ALSK+l-ARG (ALSK+l-ARG). After 21 days of treatment, only the ALSK+l-ARG group was effective in normalizing the arterial pressure (108.8±2.8 mm Hg). The l-ARG and ALSK+l-ARG groups did not show hypertrophy of the left ventricle. All the treatments restored the depressed baroreflex sensitivity to values found in the SHAM group. Acute administration of TEMPOL restored the depressed baroreflex sensitivity in the 2K1C group to values that resembled those presented by the other groups. All treatments were effective for an increase in the antioxidant pathway and reduction in the oxidative pathway. In conclusion, the treatment with ALSK or l-ARG reduced oxidative stress and restored reduced baroreflex sensitivity in renovascular hypertension. In addition, the treatments were able to normalize blood pressure and reverse left ventricular hypertrophy when used in combination.

  10. Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

    Science.gov (United States)

    Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

    2013-01-01

    Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  11. Signifiance of Arginine 20 in the 2A protease for swine vesicular disease virus pathogenicity

    DEFF Research Database (Denmark)

    Inoue, Toru; Zhang, Zhidong; Wang, Leyuan

    2007-01-01

    of the 2A protease is particularly significant. Inoculation of pigs with mutant viruses containing single amino acid substitutions at this residue leads to the appearance of revertants, often containing an arginine at this position encoded by an AGA codon, one of six codons for this residue. The properties...

  12. Structural Basis for EarP-Mediated Arginine Glycosylation of Translation Elongation Factor EF-P.

    Science.gov (United States)

    Krafczyk, Ralph; Macošek, Jakub; Jagtap, Pravin Kumar Ankush; Gast, Daniel; Wunder, Swetlana; Mitra, Prithiba; Jha, Amit Kumar; Rohr, Jürgen; Hoffmann-Röder, Anja; Jung, Kirsten; Hennig, Janosch; Lassak, Jürgen

    2017-09-26

    Glycosylation is a universal strategy to posttranslationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline-specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the crystal structure of EarP from Pseudomonas putida The enzyme is composed of two opposing domains with Rossmann folds, thus constituting a B pattern-type glycosyltransferase (GT-B). While dTDP-β-l-rhamnose is located within a highly conserved pocket of the C-domain, EarP recognizes the KOW-like N-domain of EF-P. Based on our data, we propose a structural model for arginine glycosylation by EarP. As EarP is essential for pathogenicity in P. aeruginosa , our study provides the basis for targeted inhibitor design. IMPORTANCE The structural and biochemical characterization of the EF-P-specific rhamnosyltransferase EarP not only provides the first molecular insights into arginine glycosylation but also lays the basis for targeted-inhibitor design against Pseudomonas aeruginosa infection. Copyright © 2017 Krafczyk et al.

  13. L-arginine increases nitric oxide and attenuates pressor and heart ...

    African Journals Online (AJOL)

    olayemitoyin

    mice, L-Arginine normalizes red blood cell density and induces Gardos ... the lying position the subjects were asked to rise to the standing position ..... This rise causes smooth muscle relaxation presumably by a decrease in intracellular Ca2+ concentration (Moncada and Higgs, 1993; Jerca et al, 2002). It is not clear why ...

  14. Erythrocytes L-arginine y+ transporter inhibition by N-ethylmaleimide in ice-bath.

    Science.gov (United States)

    Pinheiro da Costa, Bartira Ercília; de Almeida, Priscilla Barcellos; Conceição, Ioná Rosine; Antonello, Ivan Carlos Ferreira; d'Avila, Domingos O; Poli-de-Figueiredo, Carlos Eduardo

    2010-11-01

    Erythrocytes L: -arginine uptake is conveyed by y+ and y+L membrane transport systems. Pre-incubation with N-ethylmaleimide for 10 min at 37°C inhibits the y+ system. The aim of this study was to determine the ideal pre-incubation temperature in evaluating y+ and y+L systems. Cells were pre-incubated with or without N-ethylmaleimide for 10 min at 4°C and 37°C. L: -Arginine uptake was quantified by radioisotope and standard erythrocytes membrane flux methodology. Results demonstrate that erythrocytes L: -arginine content is depleted by pre-incubation at 37°C for 10 min, thus changing the V (max) measurement. The inhibitory effect of N-ethylmaleimide pre-incubation was temperature independent and already complete after 1 min of incubation. No significant difference in kinetic parameters was detected between cells pre-incubated at 37°C or 4°C, under zero-trans conditions. In conclusion, we suggest that measurement of erythrocytes L: -arginine uptake by y+ and y+L systems could be carried out without N-ethylmaleimide pre-incubation at 37°C.

  15. Arginine residues are more effective than lysine residues in eliciting the cellular uptake of onconase.

    Science.gov (United States)

    Sundlass, Nadia K; Raines, Ronald T

    2011-11-29

    Onconase is an amphibian member of the pancreatic ribonuclease family of enzymes that is in clinical trials for the treatment of cancer. Onconase, which has an abundance of lysine residues, is internalized by cancer cells through endocytosis in a mechanism similar to that of cell-penetrating peptides. Here, we compare the effect of lysine versus arginine residues on the biochemical attributes necessary for Onconase to elicit its cytotoxic activity. In the variant R-Onconase, 10 of the 12 lysine residues in Onconase are replaced with arginine, leaving only the two active-site lysines intact. Cytometric assays quantifying internalization showed a 3-fold increase in the internalization of R-Onconase compared with Onconase. R-Onconase also showed greater affinity for heparin and a 2-fold increase in ribonucleolytic activity. Nonetheless, arginine substitution endowed only a slight increase in toxicity toward human cancer cells. Analysis of denaturation induced with guanidine-HCl showed that R-Onconase has less conformational stability than does the wild-type enzyme; moreover, R-Onconase is more susceptible to proteolytic degradation. These data indicate that arginine residues are more effective than lysine in eliciting cellular internalization but can compromise other aspects of protein structure and function.

  16. Lysine and arginine content of proteins: computational analysis suggests a new tool for solubility design.

    Science.gov (United States)

    Warwicker, Jim; Charonis, Spyros; Curtis, Robin A

    2014-01-06

    Prediction and engineering of protein solubility is an important but imprecise area. While some features are routinely used, such as the avoidance of extensive non-polar surface area, scope remains for benchmarking of sequence and structural features with experimental data. We study properties in the context of experimental solubilities, protein gene expression levels, and families of abundant proteins (serum albumin and myoglobin) and their less abundant paralogues. A common feature that emerges for proteins with elevated solubility and at higher expression and abundance levels is an increased ratio of lysine content to arginine content. We suggest that the same properties of arginine that give rise to its recorded propensity for specific interaction surfaces also lead to favorable interactions at nonspecific contacts, and thus lysine is favored for proteins at relatively high concentration. A survey of protein therapeutics shows that a significant subset possesses a relatively low lysine to arginine ratio, and therefore may not be favored for high protein concentration. We conclude that modulation of lysine and arginine content could prove a useful and relatively simple addition to the toolkit available for engineering protein solubility in biotechnological applications.

  17. Differential P1 arginine and lysine recognition in the prototypical proprotein convertase Kex2

    Science.gov (United States)

    Wheatley, Joshua L.; Holyoak, Todd

    2007-01-01

    The high-resolution crystal structure of kexin (Kex2) in complex with a peptidyl-chloromethylketone inhibitor containing a noncognate lysine at the P1 position provides the structural basis for the differential lysine/arginine selectivity that defines the prohormone (proprotein) convertase (PC) family. By comparison with the previous structures of Kex2 and furin, this structure of the acylated enzyme provides a basis for the observed decrease in the acylation rate with substrates containing a lysine at P1 and the absence of an effect on the deacylation rate without involving mobility of the S1 lid. The structure of the complex shows that a secondary subsite in the S1 pocket is present, and that this site recognizes and binds the P1 lysine in a more shallow fashion than arginine. This results in a displacement of the bound peptide away from the S385 nucleophile relative to substrates containing a P1 arginine. It is concluded that this alternate binding site and resultant displacement of the scissile bond in the active site results in the observed decrease in the acylation rate. Studies of the inactivation kinetics of Kex2 by two peptidyl chloromethylketone inhibitors demonstrates that the selectivity between lysine and arginine at the P1 position arises at the acylation step, consistent with what was observed with peptidyl substrates [Rockwell NC, Fuller RS (2001) J Biol Chem 276:38394–38399]. PMID:17426142

  18. Arginine-based biodegradable ether-ester polymers with low cytotoxicity as potential gene carriers.

    Science.gov (United States)

    Memanishvili, Tamar; Zavradashvili, Nino; Kupatadze, Nino; Tugushi, David; Gverdtsiteli, Marekh; Torchilin, Vladimir P; Wandrey, Christine; Baldi, Lucia; Manoli, Sagar S; Katsarava, Ramaz

    2014-08-11

    The success of gene therapy depends on safe and effective gene carriers. Despite being widely used, synthetic vectors based on poly(ethylenimine) (PEI), poly(l-lysine) (PLL), or poly(l-arginine) (poly-Arg) are not yet fully satisfactory. Thus, both improvement of established carriers and creation of new synthetic vectors are necessary. A series of biodegradable arginine-based ether-ester polycations was developed, which consists of three main classes: amides, urethanes, and ureas. Compared to that of PEI, PLL, and poly-Arg, much lower cytotoxicity was achieved for the new cationic arginine-based ether-ester polymers. Even at polycation concentrations up to 2 mg/mL, no significant negative effect on cell viability was observed upon exposure of several cell lines (murine mammary carcinoma, human cervical adenocarcinoma, murine melanoma, and mouse fibroblast) to the new polymers. Interaction with plasmid DNA yielded compact and stable complexes. The results demonstrate the potential of arginine-based ether-ester polycations as nonviral carriers for gene therapy applications.

  19. The effect of L-arginine on contralateral testes following 720 0 ...

    African Journals Online (AJOL)

    The untreated group B presented atrophic seminiferous tubules with loss of germs cells and no luminal spermatozoon, while group D presented normal features except for interstitial hemorrhage. Normal features were observed for groups E (treated) and F (untreated). Thus, L-arginine tends to reduce oxidative stress in the ...

  20. Feed supplementation with arginine and zinc on antioxidant status and inflammatory response in challenged weanling piglets

    Directory of Open Access Journals (Sweden)

    Nadia Bergeron

    2017-09-01

    Full Text Available Although supplementing the diet with zinc oxide and arginine is known to improve growth in weanling piglets, the mechanism of action is not well understood. We measured the antioxidant status and inflammatory response in 48 weanling castrated male piglets fed diets supplemented with or without zinc oxide (2,500 mg Zn oxide per kg and arginine (1% starting at the age of 20 days. The animals were injected with lipopolysaccharide (100 μg/kg on day 5. Half of them received another injection on day 12. Blood samples were taken just before and 6, 24 and 48 h after injection and the mucosa lining the ileum was recovered following euthanizing on days 7 and 14. Zinc supplementation increased reduced and total glutathione (GSH (reduced and total during days 5 to 7 and arginine decreased oxidized GSH measured on days 5 and 12 and the ratio of total antioxidant capacity to total oxidative status during days 12 to 14. Zinc decreased plasma malondialdehyde measured on days 5 and 12 and serum haptoglobin measured on day 12 and increased both metallothionein-1 expression and total antioxidant capacity measured in the ileal mucosa on day 14. Tumour necrosis factor α concentration decreased from days 5 to 12 (all effects were significant at P < 0.05. This study shows that the zinc supplement reduced lipid oxidation and lipopolysaccharide-induced inflammation during the post-weaning period, while the arginine supplementation had only a limited effect.

  1. Preparation of Simvastatin Hydrogel through Arginine Addition for Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Rosyida Niswati Fathmah

    2018-01-01

    Full Text Available Simvastatin is a lipid lowering agent which has been used recently as drug delivery system for stimulating bone regeneration. Because of low therapeutic efficacy and bioavailability, it is necessary to deliver simvastatin by local administration e.g. by hydrogel system. However, simvastatin has very poor solubility which restricts to prepare hydrogel formulation. The aim of this study is to improve solubility of simvastatin with arginine as co-solvent for developing a controlled released drug delivery system by loading simvastatin into gelatin hydrogel. The solubility study was performed by addition of an excess mass of simvastatin into the specified molar solutions of the arginine. All conical flasks were placed in a mechanical water bath shaker at the temperature of 25, 40, and 50 °C and shaken for a maximum period of 72 hours. The drug concentration was analyzed by UV/Visible spectroscopy at 238 nm. The hydrogel was prepared by a dehydrothermal method. The results showed that simvastatin solubility increases with increasing arginine concentrations and temperature. Characterizations showed a successful preparation of simvastatin-loaded gelatin hydrogel. The arginine simvastatin hydrogel and the gelatin hydrogel (as a blank exhibited a comparable swelling index (ca. 6.5. Furthermore, microparticles of the material show a narrow particle size distribution in the range between 150-250 μm.

  2. Diurnal changes in polyamine content, arginine and ornithine decarboxylase, and diamine oxidase in tobacco leaves

    Czech Academy of Sciences Publication Activity Database

    Gemperlová, Lenka; Nováková, Marie; Vaňková, Radomíra; Eder, Josef; Cvikrová, Milena

    2006-01-01

    Roč. 57, č. 6 (2006), s. 1413-1421 ISSN 0022-0957 R&D Projects: GA ČR GA206/03/0369 Institutional research plan: CEZ:AV0Z50380511 Keywords : Arginine decarboxylase * diamine oxidase * ornithine decarboxylase Subject RIV: ED - Physiology Impact factor: 3.630, year: 2006

  3. Altitude Exposure and the Role of Hypoxia and Arginine Vasopressin in Cerebral Fluid Dynamics.

    Science.gov (United States)

    1981-12-01

    3E162777A879.BC.085 221 North Grand Blvd. ~ 1ri~amiganmir fi’A _________________ 11. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE U.S. Army Research...the influence of hypoxia upon arginine vaso - pressin (AVP) content of CSF are quite preliminary and indicate a surprisingly high concentration of AVP in

  4. L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Madsen, Andreas Nygaard; Smajilovic, Sanela

    2012-01-01

    L: -Arginine (L: -Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L: -Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity...

  5. A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

    NARCIS (Netherlands)

    G. Mondanelli (Giada); R. Bianchi (Roberta); M.T. Pallotta (Maria Teresa); C. Orabona (Ciriana); E. Albini (Elisa); A. Iacono (Alberta); M.L. Belladonna (Maria Laura); C. Vacca (Carmine); F. Fallarino (Francesca); A. Macchiarulo (Antonio); S. Ugel (Stefano); V. Bronte (Vincenzo); F. Gevi (Federica); L. Zolla (Lello); A.P. Verhaar (Auke); M.P. Peppelenbosch (Maikel); E.M.C. Mazza (Emilia Maria Cristina); S. Bicciato (Silvio); Y. Laouar (Yasmina); L. Santambrogio (Laura); P. Puccetti (Paolo); C. Volpi (Claudia); U. Grohmann (Ursula)

    2017-01-01

    textabstractArginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity

  6. The Effect of Pumpkin ( Cucurbita pepo L) Seeds and L-Arginine ...

    African Journals Online (AJOL)

    The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on androgenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in ...

  7. L-arginine signalling potential in the brain: the peripheral gets central.

    Science.gov (United States)

    Lameu, Claudiana; de Camargo, Antonio C M; Faria, Marcella

    2009-06-01

    L-arginine is a basic amino acid that has versatile metabolic roles, being involved in the generation of a wide range of biologically active intermediates such as nitric oxide (NO), polyamines, creatine and L-amino acids [1]. Because the levels of L-arginine reflect a metabolic crossroads, the mechanisms of its synthesis and degradation in peripheral tissues are very well described. However, there is an increasing amount of data also implicating this amino acid as a mediator of central nervous system activities and those are not yet fully understood. Here we shall summarize the tissue-specific pathways controlling L-arginine intracellular and blood levels and also the emerging evidence pointing to a role of this metabolite in the central regulation of diverse physiological processes, as blood pressure control and inflammatory response. As a conclusion we shall discuss the advantages of targeting L-arginine metabolism over other NO donors, as a general strategy to correct NO deficiency related diseases and discuss a few new patents recently deposited which take into account the rational perspective outlined in the present review.

  8. Effects of dietary L-arginine on orthodontic tooth movement in rats

    African Journals Online (AJOL)

    Yomi

    2012-01-03

    Jan 3, 2012 ... of orthodontic tooth movement and the number of osteoclasts were analyzed by independent sample t test and findings ... Key words: L-Arginine, dietary, orthodontic tooth movement, nitric oxide, root resorption, osteoclast, nitric oxide synthase ..... (1984). Clinical application of prostaglandin E1 (PGE1) upon.

  9. Allevation of Oxidative Damages Induced by Salinity in Cress (Lepidium sativum by Pretreating with Arginine

    Directory of Open Access Journals (Sweden)

    E Asadi karam

    2015-05-01

    Full Text Available Salinity is one of the main stresses that have negative effectcs on seedling growth, and plant production. It inhibits growth of plants through disturbance of the balance between production of ROS and antioxidant defense mechanism which results in oxidative stress. Because, arginine is a vital regulator of physiological and developmental processes the effect of different concentrations of arginine pretreatment of the plant on alleviation of oxidative stress induced by salt 50 and 100Mm NaCl was investigated. Arginine pretreatment increased chlorophyll a, b, carotenoid and seedling growth under salinity condition. Results also showed that salt stress increased proline, protein, H2O2, soluble sugar and the activity of ascorbate peroxidase, guaiacol peroxidase and catalase. Pretreatment of plants with Arg reduced proline, soluble sugar, H2O2 and antioxidant enzymes activity content significantly. The conclusion is that in garden cress plants, pretreatment with concentration of 5 µM and 10 μM arginine may protect cress under salinity stress, probably through the contracting with ROS and or induction of anti-oxidative enzymes

  10. Arginine-vasopressin content of hippocampus and amygdala during passive avoidance behavior in rats

    NARCIS (Netherlands)

    Kloet, E.R. de; Laczi, F.; Gaffori, O.; Wied, D. de

    1983-01-01

    Arginine-vasopressin (AVP) is involved in memory processes. The memory effects of AVP are mediated by neuronal mechanisms taking place in limbic-midbrain structures. Therefore, immunoreactive AVP (IR-AVP) was measured in hippocampus and amygdala of male Wistar rats during acquisition and retention

  11. Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases

    NARCIS (Netherlands)

    T.B. van Dijk (Thamar); N. Gillemans (Nynke); C. Stein (Claudia); P. Fanis (Pavlos); J.A.A. Demmers (Jeroen); M.P.C. van de Corput (Mariëtte); J. Essers (Jeroen); F.G. Grosveld (Frank); U.M. Bauer (Uta-Maria); J.N.J. Philipsen (Sjaak)

    2010-01-01

    textabstractWe describe the isolation and characterization of Friend of Prmt1 (Fop), a novel chromatin target of protein arginine methyltransferases. Human Fop is encoded by C1orf77, a gene of previously unknown function. We show that Fop is tightly associated with chromatin, and that it is modified

  12. Pathogenesis of chronic cluster headache and bouts: role of tryptamine, arginine metabolism and α1-agonists.

    Science.gov (United States)

    D'Andrea, G; Bussone, G; Di Fiore, P; Perini, F; Gucciardi, A; Bolner, A; Aguggia, M; Saracco, G; Galloni, E; Giordano, G; Leon, A

    2017-05-01

    The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

  13. l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy

    DEFF Research Database (Denmark)

    Szabo, P; Lantos, J; Nagy, L

    2016-01-01

    lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range...

  14. Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases

    DEFF Research Database (Denmark)

    Knuhtsen, Astrid; Legrand, Baptiste; Van der Poorten, Olivier

    2016-01-01

    Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-pr...

  15. Nutritional supplementation with arginine protects radiation-induced effects: an experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Flavia Cristina Morone, E-mail: fcmorone@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Campos-Silva, Pamella; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Sampaio, Francisco Jose Barcellos [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil)

    2016-10-15

    Purpose: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. Methods: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. Results: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). Conclusions: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine. (author)

  16. Thermal, FT–IR and SHG efficiency studies of L-arginine doped KDP ...

    Indian Academy of Sciences (India)

    TECS

    The crystals were evaluated by the Krutz and Perry. (1968) powder technique using a Q-switched, mode locked. Nd : YAG laser. A micro-crystalline material of KDP, available at the Indian Institute of Science, was used for comparison in the SHG measurements. 3. Results and discussion. L-arginine is one of the amino acids ...

  17. Effects of glucose and oxygen on arginine metabolism by coagulase-negative staphylococci.

    Science.gov (United States)

    Sánchez Mainar, María; Matheuse, Fréderick; De Vuyst, Luc; Leroy, Frédéric

    2017-08-01

    Coagulase-negative staphylococci (CNS) are not only part of the desirable microbiota of fermented meat products but also commonly inhabit skin and flesh wounds. Their proliferation depends on the versatility to use energy sources and the adaptation to fluctuating environmental parameters. In this study, the conversion of the amino acid arginine by two strains with arginine deiminase (ADI) activity (Staphylococcus carnosus 833 and S. pasteuri αs3-13) and a strain with nitric oxide synthase (NOS) activity (S. haemolyticus G110) was modelled as a function of glucose and oxygen availability. Both factors moderately inhibited the ADI-based conversion kinetics, never leading to full repression. However, for NOS-driven conversion of arginine by S. haemolyticus G110, oxygen was an absolute requirement. When changing from microaerobic conditions to aerobiosis, a switch from homolactic fermentation to a combined formation of lactic acid, acetic acid, and acetoin was found in all cases, after which lactic acid and acetic acid were used as substrates. The kinetic model proposed provided a suitable description of the data of glucose and arginine co-metabolism as a function of oxygen levels and may serve as a tool to further analyse the behaviour of staphylococci in different ecosystems or when applying specific food processing conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Loss of the arginine methyltranserase PRMT7 causes syndromic intellectual disability with microcephaly and brachydactyly.

    Science.gov (United States)

    Kernohan, K D; McBride, A; Xi, Y; Martin, N; Schwartzentruber, J; Dyment, D A; Majewski, J; Blaser, S; Boycott, K M; Chitayat, D

    2017-05-01

    Post-translational protein modifications exponentially expand the functional complement of proteins encoded by the human genome. One such modification is the covalent addition of a methyl group to arginine or lysine residues, which is used to regulate a substantial proportion of the proteome. Arginine and lysine methylation are catalyzed by protein arginine methyltransferase (PRMTs) and protein lysine methyltransferase proteins (PKMTs), respectively; each methyltransferase has a specific set of target substrates. Here, we report a male with severe intellectual disability, facial dysmorphism, microcephaly, short stature, brachydactyly, cryptorchidism and seizures who was found to have a homozygous 15,309 bp deletion encompassing the transcription start site of PRMT7, which we confirmed is functionally a null allele. We show that the patient's cells have decreased levels of protein arginine methylation, and that affected proteins include the essential histones, H2B and H4. Finally, we demonstrate that patient cells have altered Wnt signaling, which may have contributed to the skeletal abnormalities. Our findings confirm the recent disease association of PRMT7, expand the phenotypic manifestations of this disorder and provide insight into the molecular pathogenesis of this new condition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Gas-phase salt bridge interactions between glutamic acid and arginine

    NARCIS (Netherlands)

    Jaeqx, S.; Oomens, J.; Rijs, A.M.

    2013-01-01

    The gas-phase side chain-side chain (SC-SC) interaction and possible proton transfer between glutamic acid (Glu) and arginine (Arg) residues are studied under low-temperature conditions in an overall neutral peptide. Conformation-specific IR spectra, obtained with the free electron laser FELIX, in

  20. Arginine and vitamin E improve the immune response after a Salmonella challenge in broiler chicks

    Science.gov (United States)

    Two experiments were conducted to evaluate the effects of arginine (ARG), vitamin E (VE), and mannanoligosaccharide (MOS) on the immune response and clearance of Salmonella in broiler chickens. In each experiment, chicks were randomly distributed into 4 groups: antibiotic-free diet (negative contro...

  1. Oral L-arginine supplementation and faecal calprotectin levels in very low birth weight neonates.

    Science.gov (United States)

    Polycarpou, E; Zachaki, S; Papaevangelou, V; Tsolia, M; Kyriacou, A; Kostalos, C; Kafetzis, D

    2013-02-01

    The objective of this study is to determine the potential effect of oral L-arginine supplementation on intestinal inflammation in very low birth weight (VLBW) neonates, as estimated by faecal calprotectin levels. The study enrolled 83 VLBW neonates with birth weight ≤1500 g and gestational age ≤34 weeks. In this double-blind study, 40 neonates received daily oral L-arginine supplementation of 1.5 mmol kg(-1) per day between the 3rd and 28th day of life, and 43 neonates placebo. Stool samples were collected on days 3, 14 and 28, and calprotectin was measured by enzyme-linked immunosorbent assay. Calprotectin values significantly decreased over time in both groups (P=0.032). No difference in faecal calprotectin values was recorded between neonates receiving arginine supplementation and neonates receiving placebo at days 3, 14 and 28. Faecal calprotectin values decrease with increasing postnatal age in VLBW infants, but this is not related to arginine supplementation.

  2. l-Arginine supplementation enhances antioxidant activity and erythrocyte integrity in sickle cell anaemia subjects.

    Science.gov (United States)

    Kehinde, M O; Ogungbemi, S I; Anigbogu, C N; Jaja, S I

    2015-09-01

    The effect of oral, low-dose l-arginine supplementation (1g/day for 6 weeks) on antioxidant activity, haematological parameters and osmotic fragility of red blood cells was investigated in sickle cell disease sufferers. Twenty eight sickle cell anaemia subjects were recruited for the study. Five millilitres of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), total antioxidant enzymes (TAE) activity, malondialdehyde concentration ([MDA]), RBC count, [Hb], PCV, MCHC, MCV, MCH, percent irreversibly sickled cells (%ISC)) and osmotic fragility of red blood cells in the subjects. l-arginine supplementation increased [R] (pSupplementation shifted the osmotic fragiligram to the right and reduced the concentrations of NaCl at which initial and complete lyses of erythrocytes occurred. Study showed that low-dose, oral l-arginine increased antioxidant activity, red blood cell resistance to osmotic lysis but reduced red cell density in SCD. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Synergistic Protection of L-Arginine and Vitamin E On Lipid Peroxidation of Asthenospermic Patients

    Directory of Open Access Journals (Sweden)

    Sudha Srivastava

    2008-01-01

    Full Text Available Background: Lipid peroxidation is known to cause various impairments to sperm cells and mayplay a major role in the etiology of male infertility. Asthenospermia is the main factor of maleinfertility and has significantly higher level of peroxidation than in normozoospermic males.Materials and Methods: Using thiobarbituric acid (TBA assay procedure, we have determinedthe level of lipid peroxidation as indicated by malondialdehyde (MDA in the spermatozoa obtainedfrom asthenospermic male semen.Results: An inverse correlation of MDA concentration with sperm motility is observed. Treatmentof cells with L-arginine and vitamin E significantly decreases the MDA concentration and improvesthe sperm motility as compared to that in case of control samples. A combination of L-arginine andvitamin E shows synergistic effect on sperm motility and prevention of lipid peroxidation.Conclusion: L-arginine and vitamin E protect the cells against the loss of sperm motility by lipidperoxidation. Therefore, supplementation of both L-arginine and vitamin E may improve spermmotility and increase the possibility of fertilization in asthenospermic subjects.

  4. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

    Directory of Open Access Journals (Sweden)

    Amal Abdussalam Ali A. Hmaid

    2018-03-01

    Full Text Available Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C or cold (4 ± 1 °C and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis. Keywords: Cardiomyocyte, Cardiac hypertrophy, l-Arginine, l-NAME, Myocardium

  5. Dietary L-arginine supplementation modulates lipopolysaccharide-induced systemic inflammatory response in broiler chickens

    Science.gov (United States)

    This study was conducted to evaluate whether dietary supplementation with L-arginine (Arg) could attenuate lipopolysaccharide (LPS)-induced systemic inflammatory response through LPS/TLR-4 signaling pathway in broilers. The experiment was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatm...

  6. Monitoring of L-Arginine and Endogenous Dimethylarginines in Survivor Septic Patients - A Pilot Study.

    Science.gov (United States)

    Németh, Balázs; Kiss, István; Péter, Iván; Ajtay, Zénó; Németh, Ádám; Márk, László; Csorba, Attila; Kőszegi, Tamás; Mühl, Diána; Kustán, Péter

    Nitric oxide (NO) pathway plays a major role in the development and advancement of inflammation. We aimed to design a study and investigate its feasibility to show the changes of L-arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), which are important regulators of the NO pathway. Concentrations of L-arginine, ADMA and SDMA were measured by liquid chromatography-tandem mass spectrometry. Seventeen septic survival patients were enrolled and blood samples were obtained on the first, third and fifth day after the diagnosis of sepsis. Sixteen non-septic matched controls were recruited. ADMA levels on admission correlated well with sequential organ failure assessment (SOFA) score. During the follow-up, L-arginine/ADMA ratio increased significantly from day 1 to day 3 (p=0.005), then decreased from day 3 to day 5 (p=0.023). This study design seems feasible to investigate changes of L-Arginine, ADMA and SDMA in sepsis survival patients. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction

    NARCIS (Netherlands)

    Maarsingh, H.; Bossenga, B. E.; Bos, I. S. T.; Volders, H. H.; Zaagsma, J.; Meurs, H.

    Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations.

  8. Dietary L-arginine supplementation attenuates lipopolysaccharide-induced inflammatory response in broiler chickens

    Science.gov (United States)

    Two experiments were conducted to investigate the effect of dietary L-arginine (Arg) supplementation on inflammatory response and innate immunity of broilers. Experiment 1 was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatment; 6 birds/cage) with 3 dietary Arg concentrations (1.05, 1.4...

  9. The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis

    DEFF Research Database (Denmark)

    Molnar, Tihamer; Pusch, Gabriella; Papp, Viktoria

    2014-01-01

    ) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy...... subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring. RESULTS: Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting......CRP. Concentrations of L-arginine and hsCRP at 72 poststroke hours, respectively, were independent predictors of poststroke infection. S100 B level measured within 6 hours after the onset of AIS and hsCRP at 72 poststroke hours were independent predictors of death. CONCLUSIONS: Metabolites of the L-arginine pathway...

  10. Growth and characterization of pure and doped NLO L-arginine ...

    Indian Academy of Sciences (India)

    Single crystals of pure, Cu2+ and Mg2+ doped L-arginine acetate (LAA) were grown successfully by slow evaporation technique. In order to improve the device characteristics of LAA crystals, metal dopants of Cu2+ and Mg2+ were incorporated into the parent crystals. The grown pure and doped crystals were confirmed by ...

  11. Arginine-Based Inhibitors of Nitric Oxide Synthase: Therapeutic Potential and Challenges

    Czech Academy of Sciences Publication Activity Database

    Víteček, J.; Lojek, Antonín; Valacchi, G.; Kubala, Lukáš

    2012-01-01

    Roč. 2012, č. 2012 (2012), ID 318087 ISSN 0962-9351 R&D Projects: GA ČR(CZ) GA524/08/1753 Institutional support: RVO:68081707 Keywords : METHYL-L- ARGININE * HIGHLY SELECTIVE INHIBITORS * CARDIOVASCULAR RISK-FACTOR Subject RIV: BO - Biophysics Impact factor: 3.882, year: 2012

  12. Chronic exercise reduces platelet activation in hypertension: upregulation of the L-arginine-nitric oxide pathway.

    Science.gov (United States)

    de Meirelles, L R; Mendes-Ribeiro, A C; Mendes, M A P; da Silva, M N S B; Ellory, J C John Clive; Mann, G E; Brunini, T M C

    2009-02-01

    Nitric oxide (NO) inhibits platelet function and plays a key role in the regulation of cardiovascular homeostasis. Essential hypertension is characterized by an increased risk of thrombus formation, and by an inhibition of intraplatelet NO bioactivity. We have previously shown that membrane transport of L-arginine is a rate-limiting step for platelet-derived NO synthesis. This study examined the effects of exercise on the platelet L-arginine-NO pathway and aggregation and systemic inflammation markers in 13 sedentary hypertensive patients subjected to 60 min of training activity (exercise group), predominantly aerobic, three times a week for a period of 12 weeks. Six sedentary hypertensive patients participated in the control group. After 12 weeks, L-arginine transport was significantly increased and associated with increased platelet NO synthase activity and cGMP levels and reduced platelet aggregation. Moreover, exercise training reduced plasma concentrations of fibrinogen and C-reactive protein and blood pressure. The control group did not change their previous intraplatelet L-arginine-NO results and systemic inflammatory markers levels. Thus, exercise training reduces inflammatory responses, restores NO synthesis in platelets and thereby contributes to the beneficial effects of exercise in hypertension. The present study adds exercise as a new tool to reduce morbidity and mortality associated with platelet activation in hypertension.

  13. Periodical low eggshell temperatures during incubation and post hatch dietary arginine supplementation

    NARCIS (Netherlands)

    Afsarian, O.; Shahir, M.H.; Akhlaghi, A.; Lotfolahian, H.; Hoseini, A.; Lourens, A.

    2016-01-01

    An experiment was conducted to evaluate the effects of a periodically low eggshell temperature exposure during incubation and dietary supplementation of arginine on performance, ascites incidence, and cold tolerance acquisition in broilers. A total of 2,400 hatching eggs were randomly assigned to

  14. Arginine supplementation does not alter nitrogen metabolism of beef steers during a lipopolysaccharide challenge

    Science.gov (United States)

    Demand for arginine (Arg) is reported to increase during immune challenges. This study evaluated effects of lipopolysaccharide (LPS) and abomasal Arg infusion on nitrogen (N) metabolism and immune response of 20 ruminally cannulated steers (369 ± 46 kg BW) in a randomized block design. Each block co...

  15. Guanidinium Cations Pair with Positively Charged Arginine Side Chains in Water

    Czech Academy of Sciences Publication Activity Database

    Kubíčková, A.; Křížek, T.; Coufal, P.; Wernersson, Erik; Heyda, Jan; Jungwirth, Pavel

    2011-01-01

    Roč. 2, č. 12 (2011), s. 1387-1389 ISSN 1948-7185 R&D Projects: GA ČR GA203/08/0114; GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : guanidinium * cations * arginine * electrophoresis * water Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 6.213, year: 2011

  16. Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers

    DEFF Research Database (Denmark)

    Lenz, Elisabeth; Löbmann, Korbinian; Rades, Thomas

    2017-01-01

    was evaluated. After a polymer screening via the solvent evaporation method, co-amorphous indomethacin-arginine was prepared by a melting-solvent extrusion process without and with copovidone. The obtained products were characterized with respect to their solid-state properties, non-sink dissolution behavior...

  17. [First fixed dose combination perindopril arginine-indapamide-amlodipine: new approach in combination therapy in hypertension].

    Science.gov (United States)

    Widimský, Jiří

    2014-09-01

    Use of fixed combination of antihypertensive drugs clearly improves compliance to the pharmacological therapy, control of hypertension and prognosis. Based on the current guidelines triple antihypertensive therapy with RAS-blocker, calcium channel blocker (CCB) and diuretic represents the standard and best option. The article introduces first and innovative fixed triple combination of perindopril arginine + indapamide + amlodipine (Triplixam®). This type of therapy is suitable for patients already treated with free combinations of three antihypertensive drugs or in those hypertensives with uncontrolled hypertension on two antihypertensive molecules (approx. 60% of all hypertensive population). Fixed combination of perindopril arginine + indapamid + amlodipin is indicated also in severe hypertension (approx. 30% of pts). Large clinical data from various morbidity-mortality studies related to each of these substances are discussed as well as basic pharmacological characteristics. Based on the results from ADVANCE-CCB study combination of perindopril arginine + indapamide + CCB decreases total mortality in hypertension by 28%. Another discussed study-PIANIST confirmed significant antihypertensive effect of Triplixam® on large sample of patients with various stages of hypertension. Triplixam® in addition to that has very good tolerance with low side effects profile, flexibility of the dosages and large body of evidence of positive impact on prognosis of hypertensive patients. Use of Triplixam® may improve control of hypertension in the Czech Republic.Key words: amlodipine - fixed combination - hypertension - indapamide - perindopril arginine - therapy.

  18. Effect of arginase inhibition on pulmonary L-arginine metabolism in murine Pseudomonas pneumonia.

    Directory of Open Access Journals (Sweden)

    Anne Mehl

    Full Text Available RATIONALE: Infection of the lung with Pseudomonas aeruginosa results in upregulation of nitric oxide synthases (NOS and arginase expression, and both enzymes compete for L-arginine as substrate. Nitric oxide (NO production may be regulated by arginase as it controls L-arginine availability for NOS. We here studied the effect of systemic arginase inhibition on pulmonary L-arginine metabolism in Pseudomonas pneumonia in the mouse. METHODS: Mice (C57BL/6, 8-10 weeks old, female underwent direct tracheal instillation of Pseudomonas (PAO-1-coated agar beads and were treated by repeated intra-peritoneal injections of the arginase inhibitor 2(S-amino-6-boronohexanoic acid (ABH or PBS until lungs were harvested on day 3 of the infection. L-arginine metabolites were quantified using liquid chromatography-tandem mass spectrometry, NO metabolites nitrate and nitrite by Griess reagent and cytokines by ELISA. RESULTS: NO metabolite concentrations (48.5±2.9 vs. 10.9±2.3 µM, p<0.0001, as well as L-ornithine (29.6±1.7 vs 2.3±0.4 µM, p<0.0001, the product of arginase activity, were increased in Pseudomonas infected lungs compared to naïve controls. Concentrations of the NOS inhibitor asymmetric dimethylarginine (ADMA were also increased (0.44±0.02 vs. 0.16±0.01 µM, p<0.0001. Arginase inhibition in the infected animals resulted in a significant decrease in L-ornithine (14.6±1.6 µM, p<0.0001 but increase in L-arginine concentration (p<0.001, L-arginine/ADMA ratio (p<0.001, L-arginine availability for NOS (p<0.001, and NO metabolite concentrations (67.3±5.7 µM, p<0.05. Arginase inhibitor treatment also resulted in an increase in NO metabolite levels in animals following intratracheal injection of LPS (p = 0.015. Arginase inhibition was not associated with an increase in inflammatory markers (IFN-γ, IL-1β, IL-6, MIP-2, KC or TNF-α in lung. Concentrations of the L-ornithine-dependent polyamines putrescine, spermidine and spermine were increased

  19. Energetics of arginine and lysine transport by whole cells and membrane vesicles of strain SR, a monensin-sensitive ruminal bacterium.

    OpenAIRE

    Van Kessel, J S; Russell, J B

    1992-01-01

    Strain SR, a monensin-sensitive, ammonia-producing ruminal bacterium, grew rapidly on arginine and lysine, but only if sodium was present. Arginine transport could be driven by either an electrical potential or a chemical gradient of sodium. Arginine was converted to ornithine, and it appeared that ornithine efflux created a sodium gradient which in turn drove arginine transport. There was a linear decline in arginine transport as pH was decreased from 7.5 to 5.5, and the cells did not grow a...

  20. Converting the Yeast Arginine Can1 Permease to a Lysine Permease*

    Science.gov (United States)

    Ghaddar, Kassem; Krammer, Eva-Maria; Mihajlovic, Natalija; Brohée, Sylvain; André, Bruno; Prévost, Martine

    2014-01-01

    Amino acid uptake in yeast cells is mediated by about 16 plasma membrane permeases, most of which belong to the amino acid-polyamine-organocation (APC) transporter family. These proteins display various substrate specificity ranges. For instance, the general amino acid permease Gap1 transports all amino acids, whereas Can1 and Lyp1 catalyze specific uptake of arginine and lysine, respectively. Although Can1 and Lyp1 have different narrow substrate specificities, they are close homologs. Here we investigated the molecular rules determining the substrate specificity of the H+-driven arginine-specific permease Can1. Using a Can1-Lyp1 sequence alignment as a guideline and a three-dimensional Can1 structural model based on the crystal structure of the bacterial APC family arginine/agmatine antiporter, we introduced amino acid substitutions liable to alter Can1 substrate specificity. We show that the single substitution T456S results in a Can1 variant transporting lysine in addition to arginine and that the combined substitutions T456S and S176N convert Can1 to a Lyp1-like permease. Replacement of a highly conserved glutamate in the Can1 binding site leads to variants (E184Q and E184A) incapable of any amino acid transport, pointing to a potential role for this glutamate in H+ coupling. Measurements of the kinetic parameters of arginine and lysine uptake by the wild-type and mutant Can1 permeases, together with docking calculations for each amino acid in their binding site, suggest a model in which residues at positions 176 and 456 confer substrate selectivity at the ligand-binding stage and/or in the course of conformational changes required for transport. PMID:24448798

  1. Arginine and lysine decarboxylases and the acid tolerance response of Salmonella Typhimurium.

    Science.gov (United States)

    Alvarez-Ordóñez, Avelino; Fernández, Ana; Bernardo, Ana; López, Mercedes

    2010-01-01

    Salmonella Typhimurium CECT 443 inactivation at pH 2.5 in Mineral Medium (MM) and MM supplemented with 0.01% (w/v) arginine, lysine or glutamic acid was studied using stationary-phase cells grown in buffered BHI pH 7.0 (non-acid adapted cells) and acidified BHI up to pH 4.5 with acetic, citric, lactic and hydrochloric acids (acid adapted cells). In all cases, acid adapted cells, with D-values ranging from 23.34 to 86.90 min, showed a significantly higher acid resistance than non-acid adapted cells, with D-values between 8.90 and 10.29 min. Whereas the conditions used for acid adaptation did not exert a significant effect on the acid resistance of the S. Typhimurium CECT 443 resulting cells, the inclusion of lysine and arginine in the challenge medium protected them against acid inactivation, reaching D-values of about 2 and 3 times higher, respectively, than those found in MM or MM supplemented with glutamic acid. None of these three amino acids significantly modified the acid resistance of non-acid adapted cells. The relative expression level of adiA (encoding the arginine decarboxylase), adiY (encoding the transcriptional activator of adiA), cadA (encoding the lysine decarboxylase) and cadB (encoding the lysine/cadaverine transport protein) was examined by quantitative PCR. Acid adapted cells showed higher relative expression levels for both systems, arginine decarboxylase and lysine decarboxylase, which demonstrates that the induction of specialized pH-homeostatic systems plays an important role in S. Typhimurium CECT 443 protection against acid stress. However, the increased acid resistance showed by acid adapted cells challenged in MM arginine or lysine free suggests the existence of other microbial survival strategies. 2009 Elsevier B.V. All rights reserved.

  2. EFFECTS OF ARGININE AND VITAMIN E SUPPLEMENTED DIETS ON THE IMMUNOLOGICAL RESPONSE OF BROILERS CHICKENS

    Directory of Open Access Journals (Sweden)

    David Jesús Chan Diaz

    2012-08-01

    Full Text Available In order to evaluate the effect of arginine and vitamin E supplementation in broiler chicken diets on the immune response during post-vaccine stress, a trial was conducted with 700 chicks (1 day-old which were distributed into 28 floor-pens and fed one of four dietary treatments (with 7 replicates randomly assigned: T1 = control diet (1.31 % of arginine and 10 IU of vitamin E/kg of feed; T2 = T1 + 0.3 % of arginine; T3 = T1 + 70 IU of vitamin E; T4 = T1 + 0.3 % of arginine + 70 IU of vitamin E. At 12 days of age, all birds were vaccinated against Newcastle disease virus (ND, infectious bronchitis, avian influenza (AI and fowl pox. The traits evaluated were: post-vaccine reaction at days 14, 16, 18, 21 and 23; antibody titers against ND and AI, and relative lymphoid organs weight at days 11, 19 and 26; and the performance were recorded weekly. Chickens fed T2, T4 (at day 16, and T3 (at day 21 had lesser (p≤0.05 post-vaccine reaction than birds fed T1. The antibody titers against ND (at day 11 was higher (p≤0.05 in chickens fed T4 (3.1, T3 (2.7 and T2 (2.7 compared to T1 (1.6; meanwhile, for AI titers no differences were found. There were no differences, neither for immune organs weight, nor for performance. In conclusion, arginine and vitamin E supplementation in broiler chicken diets reduced the post-vaccine stress and improved the immune response without affecting the performance.

  3. Supplemental arginine above the requirement during suckling causes obesity and insulin resistance in rats.

    Science.gov (United States)

    Otani, Lila; Mori, Tomomi; Koyama, Ayaka; Takahashi, Shin-Ichiro; Kato, Hisanori

    2016-06-01

    Nutrition in early life is important in determining susceptibility to adult obesity, and arginine may promote growth acceleration in infants. We hypothesized that maternal arginine supplementation may promote growth in their pups and contribute to obesity and alteration of the metabolic system in later life. Dams and pups of Wistar rats were given a normal diet (15% protein) as a control (CN) or a normal diet with 2% arginine (ARG). Altered profiles of free amino acids in breast milk were observed in that the concentrations of threonine and glycine were lower in the ARG dams compared with the CN dams. The offspring of the CN and ARG dams were further subdivided into normal-diet (CN-CN and ARG-CN) groups and a high fat-diet groups (CN-HF and ARG-HF). In response to the high fat-diet feeding, the visceral fat deposits were significantly increased in the ARG-HF group (although not compared with the CN-HF group); no difference was observed between the CN-CN and ARG-CN groups. The blood glucose and insulin levels after glucose loading were significantly higher in the ARG-HF group compared with the CN-HF group. The results suggest that the offspring of dams supplemented with arginine during lactation acquired increased susceptibility to a high-fat diet, resulting in visceral obesity and insulin resistance. The lower supply of threonine and glycine to pups may be one of the contributing causes to the programming of lifelong obesity risk in offspring. Our findings also indicated that maternal arginine supplementation during suckling causes obesity and insulin resistance in rats. Copyright © 2016. Published by Elsevier Inc.

  4. Glutamine, glutamate, and arginine-based acid resistance in Lactobacillus reuteri.

    Science.gov (United States)

    Teixeira, Januana S; Seeras, Arisha; Sanchez-Maldonado, Alma Fernanda; Zhang, Chonggang; Su, Marcia Shu-Wei; Gänzle, Michael G

    2014-09-01

    This study aimed to determine whether glutamine deamidation improves acid resistance of Lactobacillus reuteri, and to assess whether arginine, glutamine, and glutamate-mediated acid resistance are redundant or complementary mechanisms of acid resistance. Three putative glutaminase genes, gls1, gls2, and gls3, were identified in L. reuteri 100-23. All three genes were expressed during growth in mMRS and wheat sourdough. L. reuteri consistently over-expressed gls3 and the glutamate decarboxylase gadB. L. reuteri 100-23ΔgadB over-expressed gls3 and the arginine deiminase gene adi. Analysis of the survival of L. reuteri in acidic conditions revealed that arginine conversion is effective at pH of 3.5 while glutamine or glutamate conversion were effective at pH of 2.5. Arginine conversion increased the pHin but not ΔΨ; glutamate decarboxylation had only a minor effect on the pHin but increased the ΔΨ. This study demonstrates that glutamine deamidation increases the acid resistance of L. reuteri independent of glutamate decarboxylase activity. Arginine and glutamine/glutamate conversions confer resistance to lactate at pH of 3.5 and phosphate at pH of 2.5, respectively. Knowledge of L. reuteri's acid resistance improves the understanding of the adaptation of L. reuteri to intestinal ecosystems, and facilitates the selection of probiotic and starter cultures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Identification of a novel antimicrobial peptide from human hepatitis B virus core protein arginine-rich domain (ARD.

    Directory of Open Access Journals (Sweden)

    Heng-Li Chen

    Full Text Available The rise of multidrug-resistant (MDR pathogens causes an increasing challenge to public health. Antimicrobial peptides are considered a possible solution to this problem. HBV core protein (HBc contains an arginine-rich domain (ARD at its C-terminus, which consists of 16 arginine residues separated into four clusters (ARD I to IV. In this study, we demonstrated that the peptide containing the full-length ARD I-IV (HBc147-183 has a broad-spectrum antimicrobial activity at micro-molar concentrations, including some MDR and colistin (polymyxin E-resistant Acinetobacter baumannii. Furthermore, confocal fluorescence microscopy and SYTOX Green uptake assay indicated that this peptide killed Gram-negative and Gram-positive bacteria by membrane permeabilization or DNA binding. In addition, peptide ARD II-IV (HBc153-176 and ARD I-III (HBc147-167 were found to be necessary and sufficient for the activity against P. aeruginosa and K. peumoniae. The antimicrobial activity of HBc ARD peptides can be attenuated by the addition of LPS. HBc ARD peptide was shown to be capable of direct binding to the Lipid A of lipopolysaccharide (LPS in several in vitro binding assays. Peptide ARD I-IV (HBc147-183 had no detectable cytotoxicity in various tissue culture systems and a mouse animal model. In the mouse model by intraperitoneal (i.p. inoculation with Staphylococcus aureus, timely treatment by i.p. injection with ARD peptide resulted in 100-fold reduction of bacteria load in blood, liver and spleen, as well as 100% protection of inoculated animals from death. If peptide was injected when bacterial load in the blood reached its peak, the protection rate dropped to 40%. Similar results were observed in K. peumoniae using an IVIS imaging system. The finding of anti-microbial HBc ARD is discussed in the context of commensal gut microbiota, development of intrahepatic anti-viral immunity and establishment of chronic infection with HBV. Our current results suggested that

  6. Dietary arginine level and 3H-thymidine incorporation into DNA in normal and regenerating liver of weanling rats

    International Nuclear Information System (INIS)

    Zimber, A.; Elliott, T.S.; Visek, W.J.

    1986-01-01

    Male weanling Sprague-Dawley rats were fed graded amounts of arginine (0.25% - 2%) in a crystalline L-amino acid diet for 10 days. Feed intake was decreased only in the rats receiving 0.25% Arg in the diet. Weight gain and growth efficiency were lower in the rats receiving 0.25% and 0.5% dietary arginine. Orotic acid excretion was elevated 400 fold in the rats receiving less than 1% dietary arginine. Liver weights were not significantly different among groups. DNA concentration/g liver was 10% lower in the rats receiving 0.25% dietary arginine. Rats receiving less than 1% arginine had 17% less RNA/g liver and 77% less 3 H-thymidine incorporation into liver DNA. After partial hepatectomy (PH) 3 H-thymidine incorporation into liver DNA was increased by 23% on rats receiving 0.5 dietary arginine compared to sham operated controls (SOC) receiving the same diet. Incorporation of 3 H-thymidine was unchanged in PH rats as compared with SOC rats receiving 0.25% Arg. These data indicate that at least 1% of dietary arginine is required to maintain normal protein metabolism in growing male rats. There were no significant differences in any of the parameters measured when dietary Arg was 1% or 2% of the diet

  7. Transcriptome analysis shows activation of the arginine deiminase pathway in Lactococcus lactis as a response to ethanol stress.

    Science.gov (United States)

    Díez, Lorena; Solopova, Ana; Fernández-Pérez, Rocío; González, Miriam; Tenorio, Carmen; Kuipers, Oscar P; Ruiz-Larrea, Fernanda

    2017-09-18

    This paper describes the molecular response of Lactococcus lactis NZ9700 to ethanol. This strain is a well-known nisin producer and a lactic acid bacteria (LAB) model strain. Global transcriptome profiling using DNA microarrays demonstrated a bacterial adaptive response to the presence of 2% ethanol in the culture broth and differential expression of 67 genes. The highest up-regulation was detected for those genes involved in arginine degradation through the arginine deiminase (ADI) pathway (20-40 fold up-regulation). The metabolic responses to ethanol of wild type L. lactis strains were studied and compared to those of regulator-deletion mutants MG∆argR and MG∆ahrC. The results showed that in the presence of 2% ethanol those strains with an active ADI pathway reached higher growth rates when arginine was available in the culture broth than in absence of arginine. In a chemically defined medium strains with an active ADI pathway consumed arginine and produced ornithine in the presence of 2% ethanol, hence corroborating that arginine catabolism is involved in the bacterial response to ethanol. This is the first study of the L. lactis response to ethanol stress to demonstrate the relevance of arginine catabolism for bacterial adaptation and survival in an ethanol containing medium. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. A study on the effect of surface lysine to arginine mutagenesis on protein stability and structure using green fluorescent protein.

    Science.gov (United States)

    Sokalingam, Sriram; Raghunathan, Govindan; Soundrarajan, Nagasundarapandian; Lee, Sun-Gu

    2012-01-01

    Two positively charged basic amino acids, arginine and lysine, are mostly exposed to protein surface, and play important roles in protein stability by forming electrostatic interactions. In particular, the guanidinium group of arginine allows interactions in three possible directions, which enables arginine to form a larger number of electrostatic interactions compared to lysine. The higher pKa of the basic residue in arginine may also generate more stable ionic interactions than lysine. This paper reports an investigation whether the advantageous properties of arginine over lysine can be utilized to enhance protein stability. A variant of green fluorescent protein (GFP) was created by mutating the maximum possible number of lysine residues on the surface to arginines while retaining the activity. When the stability of the variant was examined under a range of denaturing conditions, the variant was relatively more stable compared to control GFP in the presence of chemical denaturants such as urea, alkaline pH and ionic detergents, but the thermal stability of the protein was not changed. The modeled structure of the variant indicated putative new salt bridges and hydrogen bond interactions that help improve the rigidity of the protein against different chemical denaturants. Structural analyses of the electrostatic interactions also confirmed that the geometric properties of the guanidinium group in arginine had such effects. On the other hand, the altered electrostatic interactions induced by the mutagenesis of surface lysines to arginines adversely affected protein folding, which decreased the productivity of the functional form of the variant. These results suggest that the surface lysine mutagenesis to arginines can be considered one of the parameters in protein stability engineering.

  9. Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine.

    Science.gov (United States)

    Madeira, Marta Sofia Morgado Dos Santos; Rolo, Eva Sofia Alves; Pires, Virgínia Maria Rico; Alfaia, Cristina Maria Riscado Pereira Mateus; Coelho, Diogo Francisco Maurício; Lopes, Paula Alexandra Antunes Brás; Martins, Susana Isabel Vargas; Pinto, Rui Manuel Amaro; Prates, José António Mestre

    2017-05-30

    In the present study, the effect of arginine and leucine supplementation, and dietary protein level, were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid sensitive factors. The experiment was conducted on fifty-four entire male pigs (Duroc × Pietrain × Large White × Landrace crossbred) from 59 to 92 kg of live weight. Each pig was randomly assigned to one of six experimental treatments (n = 9). The treatments followed a 2 × 3 factorial arrangement, providing two levels of arginine supplementation (0 vs. 1%) and three levels of basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet with 2% of leucine, RPDL). Significant interactions between arginine supplementation and protein level were observed across plasma lipids. While dietary arginine increased total lipids, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and triacylglycerols in NPD, the inverse effect was observed in RPD. Overall, dietary treatments had a minor impact on hepatic fatty acid composition. RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid. Arginine supplementation increased the gene expression of FABP1, which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content. RPD, with or without leucine addition, upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1. Arginine supplementation was responsible for a modulated effect on plasma lipids, which is dependent on dietary protein level. It consistently increased lipaemia in NPD, while reducing the correspondent metabolites in RPD. In contrast, arginine had no major impact, neither on hepatic fatty acids content nor on fatty acid composition. Likewise, leucine supplementation of RPD, regardless the presence of arginine, promoted no changes on total fatty acids in

  10. Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania (Leishmania) amazonensis wild type and arginase knockout mutants under arginine starvation.

    Science.gov (United States)

    Castilho-Martins, Emerson A; Canuto, Gisele A B; Muxel, Sandra Marcia; da Silva, Maria Fernanda Laranjeira; Floeter-Winter, Lucile Maria; Del Aguila, Carmen; López-Gonzálvez, Ángeles; Barbas, Coral

    2015-07-23

    L-arginine is an essential amino acid in Leishmania (Leishmania) amazonensis metabolism. A key enzyme for parasite L-arginine metabolism is arginase (ARG) that uses arginine to produce urea and ornithine, a precursor of polyamine pathway guaranteeing parasite replication in both insect and mammal hosts. There is an alternative pathway to produce ornithine via L-proline and glutamate, but this mechanism is not described in Leishmania. In the mammal host, two enzymes can use L-arginine as substrate, the host ARG and the induced nitric oxide synthase (iNOS) that produces nitric oxide (NO). The competition between iNOS and both parasite and host ARG can favor the success of the infection or its control. Here, we established the metabolomic profile of the polyamine pathway of wild type (WT) L. (L.) amazonensis, submitted or not to L-arginine starvation, and compared to the ARG knockout mutant (arg - ). Our results indicated that arginine starvation induces a decrease in arginine, ornithine and putrescine, but we could not detect significative level changes of spermidine, spermidine or agmatine. However, the absence of ARG on the arg- mutant induced an increase of arginine and citrulline levels, but decreased the levels of ornithine and putrescine. Similarly to the WT arginine-starved parasites, the arg-parasites presented lower levels of proline when compared to the WT. This could be indicative of an alternative pathway to surpass the enzyme or its substrate absence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis.

    Science.gov (United States)

    Chen, Juncao; Gong, Xiaoyuan; Chen, Pingyang; Luo, Kaiju; Zhang, Xiuquan

    2016-08-16

    Intrauterine growth restriction (IUGR) is associated with perinatal morbidity and mortality. Several clinical trials have reported L-arginine and sildenafil citrate had effect on intrauterine growth restriction fetuses. A meta-analysis of available randomized controlled trials (RCTs) was conducted to investigate the effects of L-arginine and sildenafil citrate on major clinical outcomes of IUGR fetuses. Systematically searched Medline, Embase, the Cochrane Library, and Clinical Trials, references of retrieved articles, and conference proceedings from 1960 to 2015. We included randomized controlled trials assessing the effects of L-arginine and sildenafil citrate on IUGR. Outcomes analyzed were the birth weight, gestational age at labor, Apgar score at 1and 5 min, the ratio of NRDS, the ratio of ICH and neonatal death, etc. Ten trials were included. Nine trials (576 patients) compared L-arginine with either placebo or no intervention. In the L-arginine treatment groups of the L-arginine trials, there was a significant increase in fetal birth weight (SMD 0.41, 95 % CI [0.24,0.58]), gestational age (SMD 0.30, 95 % CI [0.07,0.54]); L-arginine treatment group have a significant reduction in the ratio of neonatal respiratory distress syndrome (P = 0.009), intracranial hemorrhage of fetuses (P = 0.002), but the number of included studies and people on these outcomes are small. As only one trial (41 patients) compared sildenafil citrate with placebo, it was too small for reliable conclusions about possible differential effects could be drawn. The results of this meta-analysis showed that L-arginine increased birth weight and prolonged gestational age at labor of IUGR fetuses. However, further large-scale RCTs are needed to adequately assess the effect of L-arginine and Sildenafil citrate on clinical outcomes, because the number of study may be small.

  12. The prolonged intake of L-arginine-L-aspartate reduces blood lactate accumulation and oxygen consumption during submaximal exercise.

    Science.gov (United States)

    Burtscher, Martin; Brunner, Fritz; Faulhaber, Martin; Hotter, Barbara; Likar, Rudolf

    2005-09-01

    L-arginine-L-aspartate is widely used by athletes for its potentially ergogenic properties. However, only little information on its real efficacy is available from controlled studies. Therefore, we evaluated the effects of prolonged supplementation with L-arginine-L-aspartate on metabolic and cardiorespiratory responses to submaximal exercise in healthy athletes by a double blind placebo-controlled trial. Sixteen healthy male volunteers (22 ± 3 years) performed incremental cycle spiroergometry up to 150 watts before and after intake of L-arginine-L-aspartate (3 grams per day) or placebo for a period of 3 weeks. After intake of L-arginine-L-aspartate, blood lactate at 150 watts dropped from 2.8 ± 0.8 to 2.0 ± 0.9 mmol·l(-1) (p L-arginine-L-aspartate supplementation effected an increased fat utilisation at 50 watts. L-arginine and L-aspartate seem to have induced synergistic metabolic effects. L-arginine might have reduced lactic acid production by the inhibition of glycolysis and L-aspartate may have favoured fatty acid oxidation. Besides, the results indicate improved work efficiency after L-arginine-L-aspartate intake. The resulting increases of submaximal work capacity and exercise tolerance may have important implications for athletes as well as patients. Key PointsAmino acids are among the most common nutritional supplements taken by athletes. They are involved in numerous metabolic pathways that affect exercise metabolism.Three weeks of L-arginine-L-aspartate supplementation resulted in lower blood lactate concentrations and oxygen consumption, diminished glucose and enhanced fat oxidation, and reduced heart rate and ventilation during submaximal cycle exercise.This implies increased submaximal work capacity and exercise tolerance, which may have important implications for both athletes as well as patients.

  13. Vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries in vitro and increased optic disc blood flow in vivo.

    Science.gov (United States)

    Chuman, Hideki; Sugimoto, Takako; Nao-I, Nobuhisa

    2017-12-01

    This study aimed to clarify the vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries (PCAs) and to investigate changes in optic disc blood flow after an infusion of L-arginine in vivo. Vascular ring segments were mounted on a double myograph system. After obtaining maximal contraction following administration of high-K solution, L-arginine was administrated. Six volunteers received an intravenous drip infusion of 100 ml of L-arginine or saline. Changes in optic disc blood flow were measured by laser speckle flowgraphy. L-arginine relaxed high-K solution-induced contracted rabbit PCAs. Carboxy-PTIO (nitric oxide scavenger) and L-NAME (nitric oxide synthase inhibitor) inhibited L-arginine-induced relaxation in rabbit PCAs. After removal of the endothelium of the rabbit PCAs, L-arginine still relaxed rabbit PCAs. L-arginine relaxed human PCAs, despite the lack of nitric oxide production. In the L-arginine infusion group, the mean blur rate was significantly greater than that of the control group in vivo. L-arginine has both nitric oxide-dependent and independent vasodilatory effect on high K- induced contractions in isolated rabbit and human PCAs. L-arginine increased optic disc blood flow in vivo.

  14. Pb II

    African Journals Online (AJOL)

    Windows User

    ., 2009) biomaterials. However, the ..... reported for various microorganisms by various researchers (Gong et al., 2005). At biomass ... the increase in initial Pb (II) was also observed for removal of Pb (II) by loofa sponge immobilized Aspergillus.

  15. An unexpected location of the arginine catabolic mobile element (ACME in a USA300-related MRSA strain.

    Directory of Open Access Journals (Sweden)

    Mette Damkjær Bartels

    Full Text Available In methicillin resistant Staphylococcus aureus (MRSA, the arginine catabolic mobile element (ACME was initially described in USA300 (t008-ST8 where it is located downstream of the staphylococcal cassette chromosome mec (SCCmec. A common health-care associated MRSA in Copenhagen, Denmark (t024-ST8 is clonally related to USA300 and is frequently PCR positive for the ACME specific arcA-gene. This study is the first to describe an ACME element upstream of the SCCmec in MRSA. By traditional SCCmec typing schemes, the SCCmec of t024-ST8 strain M1 carries SCCmec IVa, but full sequencing of the cassette revealed that the entire J3 region had no homology to published SCCmec IVa. Within the J3 region of M1 was a 1705 bp sequence only similar to a sequence in S. haemolyticus strain JCSC1435 and 2941 bps with no homology found in GenBank. In addition to the usual direct repeats (DR at each extremity of SCCmec, M1 had two new DR between the orfX gene and the J3 region of the SCCmec. The region between the orfX DR (DR1 and DR2 contained the ccrAB4 genes. An ACME II-like element was located between DR2 and DR3. The entire 26,468 bp sequence between DR1 and DR3 was highly similar to parts of the ACME composite island of S. epidermidis strain ATCC12228. Sequencing of an ACME negative t024-ST8 strain (M299 showed that DR1 and the sequence between DR1 and DR3 was missing. The finding of a mobile ACME II-like element inserted downstream of orfX and upstream of SCCmec indicates a novel recombination between staphylococcal species.

  16. Fluorescence histochemistry of peptide hormone-producing cells: observations on the phenanthrenequinone method for the demonstration of arginine residues.

    Science.gov (United States)

    Sundler, F; Håkanson, R

    1978-07-12

    Phenanthrenequinone is a sensitive and specific fluorescence histochemical reagent for monosubstituted guanidines. It is probable that it selectively demonstrates the guanidino group of arginine residues of proteins and peptides. Phenanthrenequinone induces moderate to intense fluorescence in gastric chief cells, parenchymal cells of the pancreas, and certain peptide hormone-producing cell types such as the GH cells of the adenohypophysis and the glucagon cells of the pancreatic islets. Similar fluorescence spectra were obtained from an arginine-containing peptide in a histochemical model and from the GH cells of the adenohypophysis following exposure to phenanthrenequinone. We conclude that the cells demonstrated with this reagent store peptides or proteins rich in arginine.

  17. Inversion of allosteric effect of arginine on N-acetylglutamate synthase, a molecular marker for evolution of tetrapods

    Directory of Open Access Journals (Sweden)

    Cabrera-Luque Juan

    2008-09-01

    Full Text Available Abstract Background The efficient conversion of ammonia, a potent neurotoxin, into non-toxic metabolites was an essential adaptation that allowed animals to move from the aquatic to terrestrial biosphere. The urea cycle converts ammonia into urea in mammals, amphibians, turtles, snails, worms and many aquatic animals and requires N-acetylglutamate (NAG, an essential allosteric activator of carbamylphosphate synthetase I (CPSI in mammals and amphibians, and carbamylphosphate synthetase III (CPSIII in fish and invertebrates. NAG-dependent CPSI and CPSIII catalyze the formation of carbamylphosphate in the first and rate limiting step of ureagenesis. NAG is produced enzymatically by N-acetylglutamate synthase (NAGS, which is also found in bacteria and plants as the first enzyme of arginine biosynthesis. Arginine is an allosteric inhibitor of microbial and plant NAGS, and allosteric activator of mammalian NAGS. Results Information from mutagenesis studies of E. coli and P. aeruginosa NAGS was combined with structural information from the related bacterial N-acetylglutamate kinases to identify four residues in mammalian NAGS that interact with arginine. Substitutions of these four residues were engineered in mouse NAGS and into the vertebrate-like N-acetylglutamate synthase-kinase (NAGS-K of Xanthomonas campestris, which is inhibited by arginine. All mutations resulted in arginine losing the ability to activate mouse NAGS, and inhibit X. campestris NAGS-K. To examine at what point in evolution inversion of arginine effect on NAGS occur, we cloned NAGS from fish and frogs and examined the arginine response of their corresponding proteins. Fish NAGS were partially inhibited by arginine and frog NAGS were activated by arginine. Conclusion Difference in arginine effect on bacterial and mammalian NAGS most likely stems from the difference in the type of conformational change triggered by arginine binding to these proteins. The change from arginine

  18. The Hydrophobic Region of the DmsA Twin-Arginine Leader Peptide Determines Specificity with Chaperone DmsD

    OpenAIRE

    Winstone, Tara M. L.; Tran, Vy A.; Turner, Raymond J.

    2013-01-01

    The system specific chaperone DmsD plays a role in the maturation of the catalytic subunit of dimethyl sulfoxide (DMSO) reductase, DmsA. Pre-DmsA contains a 45-amino acid twin-arginine leader peptide that is important for targeting and translocation of folded and cofactor-loaded DmsA by the twin-arginine translocase. DmsD has previously been shown to interact with the complete twin-arginine leader peptide of DmsA. In this study, isothermal titration calorimetry was used to investigate the the...

  19. A randomized pilot study of L-arginine infusion in severe falciparum malaria: preliminary safety, efficacy and pharmacokinetics.

    Directory of Open Access Journals (Sweden)

    Tsin W Yeo

    Full Text Available Decreased nitric oxide (NO and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed.In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study, patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT] were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM.Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP and diastolic blood pressure (DBP or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n = 4 showed L-arginine concentrations 40% lower than predicted from models developed in MSM.In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine.ClinicalTrials.gov NCT00616304.

  20. A Randomized Pilot Study of L-Arginine Infusion in Severe Falciparum Malaria: Preliminary Safety, Efficacy and Pharmacokinetics

    Science.gov (United States)

    Yeo, Tsin W.; Lampah, Daniel A.; Rooslamiati, Indri; Gitawati, Retno; Tjitra, Emiliana; Kenangalem, Enny; Price, Ric N.; Duffull, Stephen B.; Anstey, Nicholas M.

    2013-01-01

    Background Decreased nitric oxide (NO) and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM) without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed. Methods In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study), patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine) and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT]) were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM. Results Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP) and diastolic blood pressure (DBP) or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n = 4) showed L-arginine concentrations 40% lower than predicted from models developed in MSM. Conclusion In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine. Trial

  1. Atomic force microscopy studies on growth mechanisms of LAP crystals grown in solution containing excessive amount of L-arginine

    International Nuclear Information System (INIS)

    Geng, Y.L.; Xu, D.; Sun, D.L.; Du, W.; Liu, H.Y.; Zhang, G.H.; Wang, X.Q.

    2005-01-01

    Atomic force microscopy (AFM) has been used to investigate the growth mechanisms of the L-arginine phosphate monohydrate (LAP) crystal grown from the aqueous solution containing excessive amount of L-arginine molecules. Under this condition, the LAP crystals grow by both 2D nucleation mechanism and spiral dislocation mechanism. 2D nucleation growth is the intrinsical growth mechanism owing to the crystal structure of LAP. The spiral growth mechanism probably results from the distortion of the crystal lattices produced by the LA n P unit or separated L-arginine molecule. Pinning points of impurities and curved step type induced by them are also explored

  2. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  3. Maintenance of cytosolic calcium is crucial to extend l-arginine therapeutic benefits during continuous dosing.

    Science.gov (United States)

    Mohan, Srinidi; Harding, Lisa

    2016-10-01

    The therapeutic benefits associated with short-term l-arginine supplementation are lost during continuous dosing. AMP-activated protein kinase (AMPK) functional modulation has been correlated with l-arginine therapeutic effectiveness, and with tolerance development during continuous supplementation. However, the metabolic link that is responsible for AMPK functional modulation during continuous l-arginine exposure is currently not known. To explore this, we incubated HUVECs for 7 days with 100 μmol/L l-arginine, in the presence or absence of other agents; and monitored their effects for eNOS function, and on tolerance sparing effects (viz, cellular glucose accumulation, and oxidative stress). HUVEC co-incubation with 100 μmol/L l-arginine and ≤1200 mg/mL calcium (Ca 2+ ) for 7 days avoided tolerance development, with an at least 1-fold increase in the eNOS and AMPK functional activity; and an 1-fold increase in overall cellular glucose uptake. The overall cellular cytosolic Ca 2+ was below 200 nmol/L, with no change in cellular glucose and superoxide/peroxynitrite (O 2 •- /ONOO - ) level from control. However, tolerance sparing effects of at least 70% decrease in eNOS and AMPK functional response, with an 1-fold reduction in glucose uptake, and at least 2-fold increase in O 2 •- /ONOO - were observed in cells exposed for 7 days to 100 μmol/L l-arginine at Ca 2+ co-incubation concentration of >1200 mg/mL. The >1200 mg/mL Ca2+ co-incubation condition, also improved the overall cellular Ca 2+ to >200 nmol/L. Similar tolerance response was observed in cells co-treated with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ in the presence of Ca 2+ influx inhibitor (20 μmol/L 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid), or eNOS activity inhibitor (30 μmol/L l-N G -nitroarginine methyl ester). No tolerance response was seen in cells incubated for 7 days with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ ; even in the presence of the inhibitor for

  4. Arginine-based cationic liposomes for efficient in vitro plasmid DNA delivery with low cytotoxicity

    Directory of Open Access Journals (Sweden)

    Sarker SR

    2013-04-01

    Full Text Available Satya Ranjan Sarker, Yumiko Aoshima, Ryosuke Hokama, Takafumi Inoue, Keitaro Sou, Shinji Takeoka Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Tokyo, Japan Background: Currently available gene delivery vehicles have many limitations such as low gene delivery efficiency and high cytotoxicity. To overcome these drawbacks, we designed and synthesized two cationic lipids comprised of n-tetradecyl alcohol as the hydrophobic moiety, 3-hydrocarbon chain as the spacer, and different counterions (eg, hydrogen chloride [HCl] salt or trifluoroacetic acid [TFA] salt in the arginine head group. Methods: Cationic lipids were hydrated in 4-(2-hydroxyethyl-1-piperazineethanesulfonic acid (HEPES buffer to prepare cationic liposomes and characterized in terms of their size, zeta potential, phase transition temperature, and morphology. Lipoplexes were then prepared and characterized in terms of their size and zeta potential in the absence or presence of serum. The morphology of the lipoplexes was determined using transmission electron microscopy and atomic force microscopy. The gene delivery efficiency was evaluated in neuronal cells and HeLa cells and compared with that of lysine-based cationic assemblies and Lipofectamine™ 2000. The cytotoxicity level of the cationic lipids was investigated and compared with that of Lipofectamine™ 2000. Results: We synthesized arginine-based cationic lipids having different counterions (ie, HCl-salt or TFA-salt that formed cationic liposomes of around 100 nm in size. In the absence of serum, lipoplexes prepared from the arginine-based cationic liposomes and plasmid (p DNA formed large aggregates and attained a positive zeta potential. However, in the presence of serum, the lipoplexes were smaller in size and negative in zeta potential. The morphology of the lipoplexes was vesicular. Arginine-based cationic liposomes with HCl-salt showed the

  5. Anti-stress and Adaptogenic Activity of l-Arginine Supplementation

    Directory of Open Access Journals (Sweden)

    Vanita Gupta

    2005-01-01

    Full Text Available In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C–hypoxia (428 mmHg–restraint (C-H-R animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C during C-H-R exposure and its recovery to Trec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining Trec 23°C and Trec 37°C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining Trec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA, blood lactate dehydrogenase (LDH and a decrease in blood catalase (CAT and plasma testosterone levels. On recovery (Trec 37°C of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD, CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2% on attaining Trec 23°C during C-H-R exposure and on recovery to Trec 37°C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.

  6. Arginine-rich cell-penetrating peptide-modified extracellular vesicles for active macropinocytosis induction and efficient intracellular delivery.

    Science.gov (United States)

    Nakase, Ikuhiko; Noguchi, Kosuke; Aoki, Ayako; Takatani-Nakase, Tomoka; Fujii, Ikuo; Futaki, Shiroh

    2017-05-16

    Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency. Consequently, the ribosome-inactivating protein saporin-encapsulated EVs modified with hexadeca-arginine (R16) peptide effectively attained anti-cancer activity.

  7. Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Molnar, Tihamer; Pusch, Gabriella; Nagy, Lajos

    2016-01-01

    BACKGROUND: Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive...... and independent associations to outcome. METHODS: Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed...... as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. RESULTS: Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most...

  8. How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

    Science.gov (United States)

    Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

    2017-12-01

    The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

  9. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Ralph, Anna P.; Waramori, Govert; Pontororing, Gysje J.; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja; Lolong, Dina B.; Yeo, Tsin W.; Chatfield, Mark D.; Soemanto, Retno K.; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P.; Eisman, John; Price, Ric N.; Morris, Peter S.; Kelly, Paul M.; Anstey, Nicholas M.

    2013-01-01

    Background Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). Methods In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. Results 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Conclusion Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained

  10. L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Anna P Ralph

    Full Text Available Vitamin D (vitD and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB.In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis. All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339.200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture and 167 (clinical score participants. Sputum culture conversion was achieved by week 4 in 48/76 (63% participants in the active L-arginine versus 48/79 (61% in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%, and in 44/75 (59% in the active vitD versus 52/80 (65% in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%. The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes.Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes

  11. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine.

    Science.gov (United States)

    Mah, Eunice; Noh, Sang K; Ballard, Kevin D; Matos, Manuel E; Volek, Jeff S; Bruno, Richard S

    2011-11-01

    Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function.

  12. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction.

    Science.gov (United States)

    Ranjbar, Kamal; Rahmani-Nia, Farhad; Shahabpour, Elham

    2016-09-01

    Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-β and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-β and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11-25, 26-50, 51-75, and 76-150 μm), TGF-β, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11-25 and 26-50 μm diameters parallel to TGF-β overexpression. In gastrocnemius muscle, the number of arterioles/mm(2) was only increased in the 11 to 25 μm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-β and downregulation of angiostatin in MI rats.

  13. THE PROLONGED INTAKE OF L-ARGININE-L-ASPARTATE REDUCES BLOOD LACTATE ACCUMULATION AND OXYGEN CONSUMPTION DURING SUBMAXIMAL EXERCISE

    Directory of Open Access Journals (Sweden)

    Martin Burtscher

    2005-09-01

    Full Text Available L-arginine-L-aspartate is widely used by athletes for its potentially ergogenic properties. However, only little information on its real efficacy is available from controlled studies. Therefore, we evaluated the effects of prolonged supplementation with L-arginine-L-aspartate on metabolic and cardiorespiratory responses to submaximal exercise in healthy athletes by a double blind placebo-controlled trial. Sixteen healthy male volunteers (22 ± 3 years performed incremental cycle spiroergometry up to 150 watts before and after intake of L-arginine-L-aspartate (3 grams per day or placebo for a period of 3 weeks. After intake of L-arginine-L-aspartate, blood lactate at 150 watts dropped from 2.8 ± 0.8 to 2.0 ± 0.9 mmol·l-1 (p < 0.001 and total oxygen consumption during the 3-min period at 150 watts from 6.32 ± 0.51 to 5.95 ± 0.40 l (p = 0.04 compared to placebo (2.7 ± 1.1 to 2.7 ± 1.4 mmol·l-1; p = 0.9 and 6.07 ± 0.51 to 5.91 ± 0.50 l; p = 0.3. Additionally, L-arginine-L-aspartate supplementation effected an increased fat utilisation at 50 watts. L-arginine and L-aspartate seem to have induced synergistic metabolic effects. L-arginine might have reduced lactic acid production by the inhibition of glycolysis and L-aspartate may have favoured fatty acid oxidation. Besides, the results indicate improved work efficiency after L-arginine-L-aspartate intake. The resulting increases of submaximal work capacity and exercise tolerance may have important implications for athletes as well as patients

  14. Effect of l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine on ischemic heart disease risk: A Mendelian randomization study.

    Science.gov (United States)

    Au Yeung, Shiu Lun; Lin, Shi Lin; Lam, Hung San Hugh Simon; Schooling, Catherine Mary

    2016-12-01

    l-arginine is a commonly consumed dietary conditional essential amino acid found in food items and supplements, which is closely related to asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). l-arginine is thought to increase nitric oxide and be cardioprotective, whereas ADMA and SDMA may inhibit nitric oxide synthesis and increase cardiovascular disease risk. Unexpectedly, l-arginine increased mortality in a small trial. To clarify the effects of these potential targets of intervention, we assessed the risk of ischemic heart disease (IHD) by genetically determined l-arginine, ADMA, and SDMA. Single nucleotide polymorphisms (SNPs) contributing to l-arginine, ADMA, and SDMA, at genome-wide significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes-based genome-wide association study IHD case (n=60,801, ~70% myocardial infarction)-control (n=123,504) study. We obtained unconfounded estimates using instrumental variable analysis by combining the Wald estimators for each SNP, taking into account any correlation between SNPs using weighted generalized linear regression. Higher l-arginine was associated with higher risk of IHD (odds ratio [OR] 1.18 per SD increase, 95% CI 1.03-1.36) and of myocardial infarction (OR 1.29, 95% CI 1.10-1.51), based on 2 SNPs from MED23. Symmetric dimethylarginine had an OR of 1.07 per SD (95% CI 0.99-1.17) for IHD based on 5 SNPs from AGXT2. Asymmetric dimethylarginine had and OR of 1.08 per SD (95% CI 0.99-1.19) for IHD based on 4 SNPs from DDAH1. l-arginine could possibly cause IHD. Given that l-arginine occurs in many common dietary items, investigation of its health effect is required. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. L-Arginine attenuates the ethylene glycol induced urolithiasis in ininephrectomized hypertensive rats: role of KIM-1, NGAL, and NOs.

    Science.gov (United States)

    Kandhare, Amit D; Patil, Mithun V K; Bodhankar, Subhash L

    2015-05-01

    Ethylene glycol (EG) exposure caused formation of calcium oxalate crystal that led to renal failure, which is associated with higher prevalence of hypertension. L-Arginine is known to have an antioxidant and nephro-protective potential. To evaluate the effect of L-arginine against EG-induced urolithiasis in uninephrectomized hypertensive rats. Uninephrectomized male Wistar rats (180-200 g) were used to induce urinary calculi through oral administration of EG (0.75%) in distilled water. Rats were treated with either distilled water (10 mg/kg, p.o.) or telmisartan (10 mg/kg, p.o.) or Cystone (500 mg/kg, p.o.) or L-arginine (250, 500, and 1000 mg/kg, p.o.) for 28 days. Various hemodynamic, biochemical, molecular, and histological parameters were assessed in kidney and heart. Rats treated with L-arginine (500 and 1000 mg/kg) significantly restored altered relative organ weight, urine output, urine density, urinary pH, and water intake. EG-induced alterations in electrocardiographic (QRS interval, HR, and ST height) and hemodynamic (SBP, DBP, MABP, and LVEDP) abnormalities were significantly restored by L-arginine (500 and 1000 mg/kg) treatment. It also significantly restored alteration in serum and urine biochemical parameters induced by EG. The elevated oxido-nitrosative stress was also significantly decreased by L-arginine (500 and 1000 mg/kg) treatment. It also significantly down-regulated EG-induced up-regulated renal KIM-1, NGAL, eNOS, and iNOs mRNA expressions. Histological aberrations induced in the renal and cardiac tissues were also ameliorated by l-arginine treatment. L-Arginine exerts its nephro- and cardio-protective potential in EG-induced urolithiasis in uninephrectomized hypertensive rats via modulation of KIM-1, NGAL, eNOS, and iNOs mRNA expression.

  16. Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men

    OpenAIRE

    Wax Benjamin; Kavazis Andreas N; Webb Heather E; Brown Stanley P

    2012-01-01

    Abstract Background Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG) muscular strength and endurance in resistance trained and untrained men. Methods Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol...

  17. The Prolonged Intake of L-Arginine-L-Aspartate Reduces Blood Lactate Accumulation and Oxygen Consumption During Submaximal Exercise

    OpenAIRE

    Burtscher, Martin; Brunner, Fritz; Faulhaber, Martin; Hotter, Barbara; Likar, Rudolf

    2005-01-01

    L-arginine-L-aspartate is widely used by athletes for its potentially ergogenic properties. However, only little information on its real efficacy is available from controlled studies. Therefore, we evaluated the effects of prolonged supplementation with L-arginine-L-aspartate on metabolic and cardiorespiratory responses to submaximal exercise in healthy athletes by a double blind placebo-controlled trial. Sixteen healthy male volunteers (22 ± 3 years) performed incremental cycle spiroergometr...

  18. Monomeric Corynebacterium glutamicum N-acetyl glutamate kinase maintains sensitivity to L-arginine but has a lower intrinsic catalytic activity.

    Science.gov (United States)

    Huang, Yuanyuan; Li, Cheng; Zhang, Hao; Liang, Shuli; Han, Shuangyan; Lin, Ying; Yang, Xiaorong; Zheng, Suiping

    2016-02-01

    N-acetyl glutamate kinase (NAGK) is a key enzyme in the synthesis of L-arginine, and L-arginine-sensitive NAGK typically has hexameric architecture. Defining the relationship between this architecture and L-arginine inhibition can provide a foundation to identify the key amino acids involved in the allosteric regulation network of L-arginine. In the present study, the key amino acids in the N-terminal helix (N-helix) of Corynebacterium glutamicum (Cg) NAGK required for hexamer formation were determined using structural homology modeling and site-directed mutagenesis. It was also verified that hexameric architecture is required for the positive cooperativity of inhibition by L-arginine and for efficient catalysis, but that it is not the determinant of inhibition by L-arginine. Monomeric mutants retained a similar sensitivity to L-arginine as the hexameric form, indicating that monomers contain an independent, sensitive signal transduction network of L-arginine to mediate allosteric regulation. Mutation studies of CgNAGKs also revealed that amino acid residues 18-23 of the N-helix are required for inhibition by L-arginine, and that E19 may be an essential amino acid influencing the apparent affinity of L-arginine. Collectively, these studies may illuminate the basic mechanism of metabolic homeostasis of C. glutamicum.

  19. Cardio-protective effects of combined l-arginine and insulin: Mechanism and therapeutic actions in myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Venardos, Kylie M; Rajapakse, Niwanthi W; Williams, David; Hoe, Louise S; Peart, Jason N; Kaye, David M

    2015-12-15

    Reduced nitric oxide (NO) bioavailability plays a central role in the pathogenesis of myocardial ischemia-reperfusion injury (I-R), and reduced l-arginine transport via cationic amino acid transporter-1 is a key contributor to the reduced NO levels. Insulin can increase NO levels by increasing the transport of its substrate l-arginine but insulin alone exerts minimal cardiac protection in I-R. We hypothesized that combined insulin and l-arginine may provide cardioprotective effects in the setting of myocardial I-R. The effect of supplemental insulin, l-arginine and the combination was examined in cardiomyocytes exposed to hypoxia/reoxygenation and in isolated perfused mouse hearts undergoing ischemia/reperfusion. When compared to controls, cardiomyocytes treated upon reoxygenation with 1nM insulin+1mM l-arginine exhibited significant (all Pl-arginine uptake following hypoxia-reoxygenation (Pl-arginine-insulin treatment upon reperfusion significantly (all Pl-arginine or insulin treatment alone. In isolated cardiomyocytes (n=3-5), 1nM insulin caused cationic amino acid transporter-1 to redistribute to the cellular membrane from the cytosol and the effects of insulin on l-arginine uptake were partially dependent on the PI3K/Akt pathway. l-arginine-insulin treatment may be a novel strategy to ameliorate I-R injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Selective small-chemical inhibitors of protein arginine methyltransferase 5 with anti-lung cancer activity.

    Directory of Open Access Journals (Sweden)

    Gui-Mei Kong

    Full Text Available Protein arginine methyltransferase 5 (PRMT5 plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation. Oral administration of the inhibitor demonstrated antitumor activity in a lung tumor xenograft model. Thus, identified PRMT5-specific small-molecule inhibitors would help elucidate the biological roles of PRMT5 and serve as lead compounds for future drug development.

  1. Social rank modulates brain arginine vasotocin immunoreactivity in false clown anemonefish (Amphiprion ocellaris).

    Science.gov (United States)

    Iwata, Eri; Nagai, Yukiko; Sasaki, Hideaki

    2010-09-01

    The brain nanopeptide arginine vasotocin (AVT) and its mammalian homolog arginine vasopressin are involved in the regulation of social and reproductive behavior. We investigated the relationship between social rank formation and the brain AVT system in the false clown anemonefish (Amphiprion ocellaris), which forms a social rank that leads to sex differentiation in higher-ranked individuals. Tanks of three sexually immature fish were kept for 90 days and each fish's behavior was observed once a month. The social rank of each individual was distinguishable by behavior, but gonadosomatic index (GSI) did not differ significantly. The number of AVT neurons in the magnocellular layer in the preoptic area (POA) increased in subordinate individuals and declined with increasing hierarchical dominance. These results suggest that social rank formation modulates AVT production in the brain of the clown anemonefish and may influence their later sex differentiation.

  2. Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest

    DEFF Research Database (Denmark)

    Sylvestersen, Kathrine B; Horn, Heiko; Jungmichel, Stephanie

    2014-01-01

    mono-methylation (MMA) sites. We thereby identify 1,027 site-specific MMA sites on 494 human proteins, discovering numerous novel mono-methylation targets and confirming the majority of currently known MMA substrates. Nuclear RNA-binding proteins involved in RNA processing, RNA localization......, transcription, and chromatin remodeling are predominantly found modified with MMA. Despite this, MMA sites prominently are located outside RNA-binding domains as compared to the proteome-wide distribution of arginine residues. Quantification of arginine methylation in cells treated with Actinomycin D uncovers...... strong site-specific regulation of MMA sites during transcriptional arrest. Interestingly, several MMA sites are down-regulated after a few hours of transcriptional arrest. In contrast, the corresponding di-methylation or protein expression level is not altered in expression, confirming that MMA sites...

  3. Immune-modulating enteral formulations: optimum components, appropriate patients, and controversial use of arginine in sepsis.

    Science.gov (United States)

    Zhou, Minhao; Martindale, Robert G

    2007-08-01

    Nutrients have traditionally been viewed as a means to provide basic calories to sustain homeostasis. However, critically ill, surgical, and trauma patients are in a constant dynamic state between systemic inflammatory response (SIRS) and compensatory anti-inflammatory response (CARS). Results from ongoing research strongly support the use of specific nutrients to modulate the immune and/or metabolic response. These agents can now be considered therapeutic tools in the management of complex hypermetabolic diseases. The principle of using nutrients as a therapeutic strategy rather than just as "nutritional support" requires a shift in the current dogma. The most common nutrients found in currently available enteral immune-modulating formulas are omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid), antioxidants, nucleotides, glutamine, and arginine. Multiple individual reports and at least five meta-analyses using combinations of immune-modulating nutrients have reported almost uniform beneficial results. However, certain conflicting hypotheses continue to revolve around the use of arginine in septic patients.

  4. Dietary L-arginine supplementation protects weanling pigs from deoxynivalenol-induced toxicity.

    Science.gov (United States)

    Wu, Li; Liao, Peng; He, Liuqin; Feng, Zemeng; Ren, Wenkai; Yin, Jie; Duan, Jielin; Li, Tiejun; Yin, Yulong

    2015-04-15

    This study was conducted to determine the positive effects of dietary supplementation with L-arginine (Arg) on piglets fed a deoxynivalenol (DON)-contaminated diet. A total of eighteen, 28-day-old healthy weanling pigs were randomly assigned into one of three groups: uncontaminated basal diet (control group), 6 mg/kg DON-contaminated diet (DON group) and 6 mg/kg DON + 1% L-arginine (DON + ARG group). After 21 days of Arg supplementation, piglets in the DON and DON + ARG groups were challenged by feeding 6 mg/kg DON-contaminated diet for seven days. The results showed that DON resulted in damage to piglets. However, clinical parameters, including jejunal morphology, amino acid concentrations in the serum, jejunum and ileum, were improved by Arg (p supplementation with Arg exerts a protective role in pigs fed DON-contaminated diets.

  5. Growth and characterization of L-arginine sulphate: A new nanocrystal with non linear optical behaviour

    Science.gov (United States)

    Khandpekar, M. M.; Patil, Smita S.

    2013-06-01

    L-arginine combines with a variety of salts and acids to form a potential non-linear optical material. Nano crystals of L-arginine-Sulphate (LAS) have been grown from solution by the slow evaporation technique for the first time. The single phase formation has been verified by XRD studies. TEM studies confirm the formation of nanocrystallites of particle size of about 34nm. The optical absorption studies shows presence of a sharp UV cut-off region at 239.57nm. Further the presence of wide transparency window in the entire visible region shows its use for optoelectronic applications. Energy Dispersive X-ray Analysis (EDAX) confirms the presence of potassium and sulphur in the grown nanocrystal of LAS. Fungus growth has been avoided by subjecting the solution to pre-heat treatment. Preliminary studies indicate presence of non-linear optical (NLO) response.

  6. Synthesis and characterization of nonlinear optical L-arginine semi-oxalate single crystal

    Science.gov (United States)

    Vasudevan, P.; Gokul Raj, S.; Sankar, S.

    2013-04-01

    L-arginine semi-oxalate single crystals have been synthesized by slow evaporation method at room temperature. Single crystal and powder X-ray diffraction analyses has been made to confirm the triclinic structure with non-centrosymmetric space group P1. The presence of functional groups of L-arginine semi-oxalate crystals was identified and confirmed by using the Fourier transform infrared spectroscopy. Molecular structure of the grown crystal was analyzed by 1H NMR and 13C NMR studies. Optical absorption studies carried out in wavelength range from 250 nm to 1200 nm have revealed that the material is completely transparent for the entire wavelength range studied. Thermal characterization using thermogravimetric analysis and differential scanning calorimetry studies show that the crystal is thermally stable up to 146 °C. The presence of second harmonic generation of the grown crystal was tested and its efficiency was determined by using Kurtz and Perry powder technique.

  7. Synthesis and characterization of bis(thiourea)zinc chloride doped with L-arginine

    Energy Technology Data Exchange (ETDEWEB)

    Moitra, Sweta [Department of Materials Science, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032 (India); Kar, Tanusree, E-mail: mstk@iacs.res.in [Department of Materials Science, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032 (India)

    2009-09-15

    Single crystals of bis(thiourea)zinc chloride (BTZC) doped with basic amino acid L-arginine were grown successfully by slow evaporation method at ambient temperature. The doped crystals are optically better and more transparent than the pure ones having wide transmission spectra lying between 280 and 2000 nm. The comparative study of solubility curve shows a slight reduction in the solubility of the doped crystals. There is a drastic change in morphology due to doping which is also reflected in the X-ray diffraction pattern. The Fourier transform infrared spectroscopy study confirms the incorporation of L-arginine into BTZC crystal, as there is a deepening of the absorption peak at around 3200 cm{sup -1}. The second harmonic generation efficiency of the pure and the doped samples are almost same, which is equivalent to potassium dihydrogen phosphate. The doped crystals are harder than the pure one.

  8. L-arginine reduces exercise-induced increase in plasma lactate and ammonia.

    Science.gov (United States)

    Schaefer, A; Piquard, F; Geny, B; Doutreleau, S; Lampert, E; Mettauer, B; Lonsdorfer, J

    2002-08-01

    To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p L-arginine-nitric oxide (NO) pathway during exercise.

  9. Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    María R. Alberto

    2012-03-01

    Full Text Available The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC, found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively. ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

  10. Arginine Coordination in Enzymatic Phosphoryl Transfer: Evaluation of the Effect of Arg166 Mutations in Escherichia Coli Alkaline Phosphatase

    International Nuclear Information System (INIS)

    O'Brien, P.J.; Lassila, J.K.; Fenn, T.D.; Zalatan, J.G.; Herschlag, D.

    2008-01-01

    Arginine residues are commonly found in the active sites of enzymes catalyzing phosphoryl transfer reactions. Numerous site-directed mutagenesis experiments establish the importance of these residues for efficient catalysis, but their role in catalysis is not clear. To examine the role of arginine residues in the phosphoryl transfer reaction, we have measured the consequences of mutations to arginine 166 in Escherichia coli alkaline phosphatase on hydrolysis of ethyl phosphate, on individual reaction steps in the hydrolysis of the covalent enzyme-phosphoryl intermediate, and on thio substitution effects. The results show that the role of the arginine side chain extends beyond its positive charge, as the Arg166Lys mutant is as compromised in activity as Arg166Ser. Through measurement of individual reaction steps, we construct a free energy profile for the hydrolysis of the enzyme-phosphate intermediate. This analysis indicates that the arginine side chain strengthens binding by ∼3 kcal/mol and provides an additional 1-2 kcal/mol stabilization of the chemical transition state. A 2.1 (angstrom) X-ray diffraction structure of Arg166Ser AP is presented, which shows little difference in enzyme structure compared to the wild-type enzyme but shows a significant reorientation of the bound phosphate. Altogether, these results support a model in which the arginine contributes to catalysis through binding interactions and through additional transition state stabilization that may arise from complementarity of the guanidinum group to the geometry of the trigonal bipyramidal transition state

  11. Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

    Science.gov (United States)

    Andrade, Maria Emília Rabelo; Santos, Rosana das Graças Carvalho Dos; Soares, Anne Danieli Nascimento; Costa, Kátia Anunciação; Fernandes, Simone Odília Antunes; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Souza, Adna Luciana; Faria, Ana Maria Caetano; Cardoso, Valbert Nascimento

    2016-11-01

    Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). The Col group showed increased intestinal permeability (C vs Col: P supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Arginine attenuates weight loss and BT in mice with colitis. © 2015 American Society for Parenteral and Enteral Nutrition.

  12. Supplementation with L-arginine does not influence arterial blood pressure in healthy people: a randomized, double blind, trial.

    Science.gov (United States)

    Ast, J; Cieślewicz, A R; Korzeniowska, K; Bogdański, P; Kazmierczak, E; Olszewski, J; Skołuda, A; Jabłecka, A

    2011-12-01

    It cannot be excluded that supplementation with L-arginine, by improving function of endothelium and hypotensive effect, can be advantegeous in prevention of cardiovascular diseases in healthy people. However, reports about hypotensive effect of L-arginine in healthy people are unclear. Moreover, no research including ambulatory blood pressure measurement (ABPM) has been conducted so far. Therefore, the aim of our study was to show if 4-week supplementation of healthy people with L-arginine influences blood pressure measured with ABPM. The study was carried out on 19 healthy people randomized to 6 g/24-hour, 12 g/24-hours of L-arginine or placebo. ABPM was carried out 4 times: before randomization, after 2 and 4 weeks of supplementation and 2 weeks after finishing supplementation. It was found that 4 weeks of supplementation of healthy people with L-arginine (6 or 12 g/24-hour) led to nonsignificant decrease of systolic and diastolic blood pressure; the decrease was greater during night. These findings showed that supplementation with L-arginine is not necessarily advantageous in healthy people.

  13. Reverse Transcriptase-Containing Particles Induced in Rous Sarcoma Virus-Transformed Rat Cells by Arginine Deprivation

    Science.gov (United States)

    Kotler, Moshe; Weinberg, Eynat; Haspel, Osnat; Becker, Yechiel

    1972-01-01

    Incubation of rat cells transformed by Rous sarcoma virus (RSV) in an arginine-deficient medium resulted in accumulation of particles in the culture medium. Such particles did not appear when the transformed rat cells were incubated in a complete medium nor in the medium of primary rat cells which were incubated either in arginine-deficient or complete media. The particles which were released from the arginine-deprived transformed rat cells resemble C-type particles in their properties. These particles band in sucrose gradients at a density of 1.16 g/ml and contain 35S ribonucleic acid (RNA) molecules and a reverse transcriptase activity. Analysis of the cytoplasm of transformed and primary rat cells, deprived and undeprived of arginine, revealed the presence of reverse transcriptase-containing particles which banded in sucrose gradients at a density of 1.14 g/ml. These particles differed from the particles released into the medium by the arginine-deprived RSV-transformed rat cells. The deoxyribonucleic acid (DNA) molecules synthesized in vitro by the reverse transcriptase present in the particles isolated from the medium of arginine-deprived cells hybridized to RSV RNA, whereas the DNA synthesized by the cell-bound enzyme had no homology to RSV RNA. PMID:4116137

  14. The effects of infusions of arginine vasopressin or 1-deamino-8-D-arginine vasopressin on common carotid vascular resistance in conscious, Long Evans rats.

    Science.gov (United States)

    Gardiner, S M; Compton, A M; Bennett, T

    1989-05-01

    1. Intravenous infusions of arginine vasopressin or 1-deamino-8-D-arginine vasopressin (DDAVP) were given to conscious, Long Evans rats chronically instrumented with bilateral, common carotid, pulsed Doppler probes and intravascular catheters. 2. During infusion of vasopressin at 0.3 nmol min-1 there was an increase in common carotid vascular resistance with no change in mean blood pressure or heart rate. Following infusion there was a common carotid vasodilatation. 3. During infusion of vasopressin at 3.0 nmol min-1 there were increases in mean arterial blood pressure and in common carotid vascular resistances, accompanied by bilateral reductions in flow and in heart rate. Administration of (+)-(CH2)5Tyr(Et)DAVP (a V1-receptor antagonist), during the continued infusion of vasopressin, reversed the effects of the latter on mean blood pressure and heart rate; under these conditions there were increases in common carotid blood flows above baseline, in company with bilateral vasodilatations. The latter effects persisted after cessation of vasopressin infusion. 4. Infusions of DDAVP were without significant effects on any measured cardiovascular variable. 5. The results do not provide straightforward support for the claim that vasopressin acts to promote cerebral perfusion, at least when V1-receptor effects are unopposed. Furthermore, it seems likely tha the vasodilator influence of vasopressin on the common carotid vascular bed is not due to stimulation of V2-receptors.

  15. Association of arginine vasopressin receptor 1a gene polymorphisms with hepatorenal syndrome

    International Nuclear Information System (INIS)

    Wang, C.; Luo, X.; Ye, J.; Liu, S.; Miu, L.; Bao, J.; Wang, F.; Yu, Z.

    2017-01-01

    To assess the association of arginine vasopressin receptor 1a gene single nucleotide polymorphisms with type I hepatorenal syndrome. Methods: The case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou, China, from January 2012 to June 2014, and comprised patients with type I hepatorenal syndrome and individuals with cirrhosis who acted as the control group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide polymorphisms were analysed by high-resolution melting methods. Statistical analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%) were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age was 42.21+-11.30years in the hepatorenal syndrome group and 43.69+-12.60 in the control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity levels were 154.76+-51.58, 49.30+-24.67 and 33.42+-3.69 in the hepatorenal syndrome group compared to 181.26+-64.46, 41.78+-17.52 and 32.98+-4.81 among controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were found in the distributions of arginine vasopressin receptor 1a gene rs113481894 locus T allele between type I hepatorenal syndrome patients and the control group (odds ratio= 2.230; p= 0.040). Conclusion: T allele located at arginine vasopressin receptor 1a receptor promoter rs113481894 locus may be associated with the pathogenesis of type I hepatorenal syndrome. (author)

  16. [Congenital hyperlysin-arginin-ornithinuria in a mentally retarded child (author's transl)].

    Science.gov (United States)

    Plöchl, E; Jarosch, E

    1977-10-01

    Congenital hyperdibasicaminoaciduria without cystinuria was detected in a mentally but not physically retarded boy. Plasma lysine and arginine were normal, whereas plasma ornithine was decreased. Although oral or intravenous loading tests could not be performed, the history without vomiting or diarrhea, and the normal physical development indicated an unimpaired intestinal transport of basic aminoacids. Our case could be a further mutant of this transport defect which concerns the renal tubuli only.

  17. Probing the disparate effects of arginine and lysine residues on antimicrobial peptide/bilayer association.

    Science.gov (United States)

    Rice, A; Wereszczynski, J

    2017-10-01

    Antimicrobial peptides (AMPs) are key components of the innate immune response and represent promising templates for the development of broad-spectrum alternatives to conventional antibiotics. Most AMPs are short, cationic peptides that interact more strongly with negatively charged prokaryotic membranes than net neutral eukaryotic ones. Both AMPs and synthetic analogues with arginine-like side chains are more active against bacteria than those with lysine-like amine groups, though the atomistic mechanism for this increase in potency remains unclear. To examine this, we conducted comparative molecular dynamics simulations of a model negatively-charged membrane system interacting with two mutants of the AMP KR-12: one with lysine residues mutated to arginines (R-KR12) and one with arginine residues mutated to lysine (K-KR12). Simulations show that both partition analogously to the bilayer and display similar preferences for hydrogen bonding with the anionic POPGs. However, R-KR12 binds stronger to the bilayer than K-KR12 and forms significantly more hydrogen bonds, leading to considerably longer interaction times. Additional simulations with methylated R-KR12 and charge-modified K-KR12 mutants show that the extensive interaction seen in the R-KR12 system is partly due to arginine's strong atomic charge distribution, rather than being purely an effect of the greater number of hydrogen bond donors. Finally, free energy simulations reveal that both peptides are disordered in solution but form an amphipathic α-helix when inserted into the bilayer headgroup region. Overall, these results highlight the role of charge and hydrogen bond strength in peptide bilayer insertion, and offer potential insights for designing more potent analogues in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Degradation of Arginine and Other Amino Acids by Eubacterium nodatum ATCC 33099

    OpenAIRE

    Uematsu, H.; Hoshino, E.

    2011-01-01

    The utilisation of a total of 20 amino acids by Eubacterium nodatum, a predominant asaccharolytic anaerobe isolated from human periodontal pockets, was studied. Washed cells of the microorganism produced substantial amounts of acetate, butyrate and ammonia from lysine, and butyrate and ammonia from arginine as main products under anaerobic conditions. They also produced a small amount of formate from histidine. Metabolic products were not detected from any of the other 17 amino acids. These r...

  19. Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test.

    Science.gov (United States)

    Tschuor, F; Zini, E; Schellenberg, S; Wenger, M; Kaufmann, K; Furrer, D; Lutz, T A; Reusch, C E

    2011-01-01

    Cats with diabetes mellitus frequently achieve clinical remission, suggesting residual β-cell function. Responsiveness of β-cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. Diabetic cats with and without remission will have different arginine-induced insulin or glucagon response. Seventeen cats with diabetes, 7 healthy cats. Blood samples collected on admission and during subsequent IVAST. Glucose, insulin, and glucagon were measured. Response to IVAST was assessed by calculating the insulin and glucagon area under the curve (AUC) and the AUC glucagon-to-insulin ratio. Diabetic cats were treated with insulin and were followed for 18 weeks. Remission was defined as normoglycemia and disappearance of clinical signs of diabetes for ≥4 weeks, without requiring insulin. Seven diabetic cats (41%) achieved remission. On admission, blood glucose concentration was significantly lower in cats with remission (median, 389 mg/dL; range, 342-536 mg/dL) than in those without remission (median, 506 mg/dL; range, 266-738 mg/dL). After IVAST, diabetic cats with remission had higher AUC glucagon-to-insulin ratios (median, 61; range, 34-852) than did cats without remission (median, 26; range, 20-498); glucose, insulin, and glucagon AUCs were not different. Diabetic cats had lower insulin AUC than did healthy cats but comparable glucagon AUC. Diabetic cats with and without remission have similar arginine-stimulated insulin secretion on admission. Although cats with remission had lower blood glucose concentrations and higher AUC glucagon-to-insulin ratios, large overlap between groups prevents use of these parameters in clinical practice. Copyright © 2010 by the American College of Veterinary Internal Medicine.

  20. Modulating short tryptophan- and arginine-rich peptides activity by substitution with histidine.

    Science.gov (United States)

    Bacalum, Mihaela; Janosi, Lorant; Zorila, Florina; Tepes, Ana-Maria; Ionescu, Cristina; Bogdan, Elena; Hadade, Niculina; Craciun, Liviu; Grosu, Ion; Turcu, Ioan; Radu, Mihai

    2017-07-01

    High antimicrobial efficacy of short tryptophan-and arginine-rich peptides makes them good candidates in the fight against pathogens. Substitution of tryptophan and arginine by histidine could be used to modulate the peptides efficacy by optimizing their structures. The peptide (RRWWRWWRR), reported to showed good antimicrobial efficacy, was used as template, seven new analogs being designed substituting tryptophan or arginine with histidine. The peptides' efficacy was tested against E. coli, B. subtilis and S. aureus. The cytotoxicity and hemolytic effect were evaluated and the therapeutic index was inferred for each peptide. Atomic force microscopy and molecular simulation were used to analyze the effects of peptides on bacterial membrane. The substitution of tryptophan by histidine proved to strongly modulate the antimicrobial activity, mainly by changing the peptide-to-membrane binding energy. The substitution of arginine has low effect on the antimicrobial efficacy. The presence of histidine residue reduced the cytotoxic and hemolytic activity of the peptides in some cases maintaining the same efficacy against bacteria. The peptides' antimicrobial activity was correlated to the 3D-hydrophobic moment and to a simple structure-based packing parameter. The results show that some of these peptides have the potential to become good candidates to fight against bacteria. The substitution by histidine proved to fine tune the therapeutic index allowing the optimization of the peptide structure mainly by changing its binding energy and 3D-hydrophobic moment. The short tryptophan reach peptides therapeutic index can be maximized using the histidine substitution to optimize their structure. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Calendula officinalis ameliorates l-arginine-induced acute necrotizing pancreatitis in rats.

    Science.gov (United States)

    Kaur, Jagdeep; Sidhu, Shabir; Chopra, Kanwaljit; Khan, M U

    2016-12-01

    Calendula officinalis L. (Asteraceae) has been traditionally used in treating inflammation of internal organs, gastrointestinal tract ulcers and wound healing. The present study investigates the effect of ethanol extract (95%) of Calendula officinalis flowers in l-arginine induced acute necrotizing pancreatitis in rats. Rats were divided into four groups: normal control, l-arginine control, Calendula officinalis extract (COE) treated and melatonin treated (positive control), which were further divided into subgroups (24 h, day 3 and 14) according to time points. Two injections of l-arginine 2 g/kg i.p. at 1 h intervals were administered in l-arginine control, COE and melatonin-treated groups to produce acute necrotizing pancreatitis. Biochemical parameters [serum amylase, lipase, pancreatic amylase, nucleic acid content, total proteins, transforming growth factor-β1 (TGF-β1), collagen content, lipid peroxidation, reduced glutathione and nitrite/nitrate] and histopathological studies were carried out. COE treatment (400 mg/kg p.o.) was found to be beneficial. This was evidenced by significantly lowered histopathological scores (2 at day 14). Nucleic acid content (DNA 21.1 and RNA 5.44 mg/g pancreas), total proteins (0.66 mg/mL pancreas) and pancreatic amylase (1031.3 100 SU/g pancreas) were significantly improved. Marked reduction in pancreatic oxidative and nitrosative stress; collagen (122 μmoles/100 mg pancreas) and TGF-β1 (118.56 pg/mL) levels were noted. Results obtained were comparable to those of positive control. The beneficial effect of COE may be attributed to its antioxidant, antinitrosative and antifibrotic actions. Hence, the study concludes that COE promotes spontaneous repair and regeneration of the pancreas.

  2. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

    Science.gov (United States)

    Kim, P A; Voskresenskaya, O G; Kamensky, A A

    2009-06-01

    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  3. Low dose vitamin C, vitamin E or L-arginine supplementation and ...

    African Journals Online (AJOL)

    The effect of chronic low-dose supplementation with vitamin C (300mg/day for 6 weeks in adults or 100mg/day for 6 weeks in children) or vitamin E (100 IU/day for 6 weeks in adults) or L-Arginine (1g/day for 6 weeks in adults) in ameliorating the pathophysiology and combating the deleterious effects of sickle cell disease in ...

  4. Camphorquinone-10-sulfonic acid and derivatives: Convenient reagents for reversible modification of arginine residues

    OpenAIRE

    Pande, Chandra S.; Pelzig, Michal; Glass, John D.

    1980-01-01

    Camphorquinone-10-sulfonic acid hydrate was prepared by the action of selenous acid on camphor-10-sulfonic acid. Camphorquinone-10-sulfonylnorleucine was prepared either from the sulfonic acid via the sulfonyl chloride or by selenous acid oxidation of camphor-10-sulfonylnorleucine. These reagents are useful for specific, reversible modification of the guanidino groups of arginine residues. Camphorquinonesulfonic acid is a crystalline water-soluble reagent that is especially suitable for use w...

  5. Three consecutive arginines are important for the mycobacterial peptide deformylase enzyme activity.

    Science.gov (United States)

    Saxena, Rahul; Kanudia, Pavitra; Datt, Manish; Dar, Haider Hussain; Karthikeyan, Subramanian; Singh, Balvinder; Chakraborti, Pradip K

    2008-08-29

    Genes encoding the peptide deformylase enzyme (def) are present in all eubacteria and are involved in the deformylation of the N-formyl group of newly synthesized polypeptides during protein synthesis. We compared the amino acid sequences of this enzyme in different mycobacterial species and found that they are highly conserved (76% homology with 62% identity); however, when this comparison was extended to other eubacterial homologs, it emerged that the mycobacterial proteins have an insertion region containing three consecutive arginine residues (residues 77-79 in Mycobacterium tuberculosis peptide deformylase (mPDF)). Here, we demonstrate that these three arginines are important for the activity of mPDF. Circular dichroism studies of wild-type mPDF and of mPDF containing individual conservative substitutions (R77K, R78K, or R79K) or combined substitutions incorporated into a triple mutant (R77K/R78K/R79K) indicate that such mutations cause mPDF to undergo structural alterations. Molecular modeling of mPDF suggests that the three arginines are distal to the active site. Molecular dynamics simulations of wild-type and mutant mPDF structures indicate that the arginines may be involved in the stabilization of substrate binding pocket residues for their proper interaction with peptide(s). Treatment with 5'-phosphothiorate-modified antisense oligodeoxyribonucleotides directed against different regions of def from M. tuberculosis inhibits growth of Mycobacterium smegmatis in culture. Taken together, these results hold out the possibility of future design of novel mycobacteria-specific PDF inhibitors.

  6. Assay of L-Arginine in rat blood by enzymatic method

    Directory of Open Access Journals (Sweden)

    Галина Зуфарівна Гайда

    2015-11-01

    Full Text Available The study of enzymatic-chemical method of L-Arginine (Arg assay on the real samples of rat blood was done. The developed method is based on the usage of recombinant arginase I and 2,3-butandion monooxim. Urea, the final product of the reaction, is detected by fluorometry. The new method was shown to be suitable for Arg assay in biological liquids of mammalians

  7. Transient Kinetics Define a Complete Kinetic Model for Protein Arginine Methyltransferase 1*

    Science.gov (United States)

    Hu, Hao; Luo, Cheng; Zheng, Y. George

    2016-01-01

    Protein arginine methyltransferases (PRMTs) are the enzymes responsible for posttranslational methylation of protein arginine residues in eukaryotic cells, particularly within the histone tails. A detailed mechanistic model of PRMT-catalyzed methylation is currently lacking, but it is essential for understanding the functions of PRMTs in various cellular pathways and for efficient design of PRMT inhibitors as potential treatments for a range of human diseases. In this work, we used stopped-flow fluorescence in combination with global kinetic simulation to dissect the transient kinetics of PRMT1, the predominant type I arginine methyltransferase. Several important mechanistic insights were revealed. The cofactor and the peptide substrate bound to PRMT1 in a random manner and then followed a kinetically preferred pathway to generate the catalytic enzyme-cofactor-substrate ternary complex. Product release proceeded in an ordered fashion, with peptide dissociation followed by release of the byproduct S-adenosylhomocysteine. Importantly, the dissociation rate of the monomethylated intermediate from the ternary complex was much faster than the methyl transfer. Such a result provided direct evidence for distributive arginine dimethylation, which means the monomethylated substrate has to be released to solution and rebind with PRMT1 before it undergoes further methylation. In addition, cofactor binding involved a conformational transition, likely an open-to-closed conversion of the active site pocket. Further, the histone H4 peptide bound to the two active sites of the PRMT1 homodimer with differential affinities, suggesting a negative cooperativity mechanism of substrate binding. These findings provide a new mechanistic understanding of how PRMTs interact with their substrates and transfer methyl groups. PMID:27834681

  8. Study on mutual interactions and electronic structures of hyaluronan with Lysine, 6-Aminocaproic acid and Arginine.

    Science.gov (United States)

    Chytil, Martin; Trojan, Martin; Kovalenko, Alexander

    2016-05-20

    Interactions between polyelectrolytes and oppositely charged surfactants have been in a great interest for several decades, yet the conventional surfactants may cause a problem in medical applications. Interactivity between polysaccharide hyaluronan (HA) and amino acids Lysine, 6-Aminocaproic acid (6-AcA), and Arginine as an alternative system is reported. The interactions were investigated by means of rheology and electric conductance and the electronic structures were explored by the density functional theory (DFT). Lysine exhibits the strongest interaction of all, which was manifested, e.g. by nearly 6-time drop of the initial viscosity comparing with only 1.3-time lower value in the case of 6-AcA. Arginine interaction with HA was surprisingly weaker in terms of viscosity than that of Lysine due to a lower and delocalized charge density on its guanidine group. According to the DFT calculations, the binding of Lysine to HA was found to be more flexible, while Arginine creates more rigid structure with HA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Functional and Evolutionary Relationship between Arginine Biosynthesis and Prokaryotic Lysine Biosynthesis through α-Aminoadipate

    Science.gov (United States)

    Miyazaki, Junichi; Kobashi, Nobuyuki; Nishiyama, Makoto; Yamane, Hisakazu

    2001-01-01

    Our previous studies revealed that lysine is synthesized through α-aminoadipate in an extremely thermophilic bacterium, Thermus thermophilus HB27. Sequence analysis of a gene cluster involved in the lysine biosynthesis of this microorganism suggested that the conversion from α-aminoadipate to lysine proceeds in a way similar to that of arginine biosynthesis. In the present study, we cloned an argD homolog of T. thermophilus HB27 which was not included in the previously cloned lysine biosynthetic gene cluster and determined the nucleotide sequence. A knockout of the argD-like gene, now termed lysJ, in T. thermophilus HB27 showed that this gene is essential for lysine biosynthesis in this bacterium. The lysJ gene was cloned into a plasmid and overexpressed in Escherichia coli, and the LysJ protein was purified to homogeneity. When the catalytic activity of LysJ was analyzed in a reverse reaction in the putative pathway, LysJ was found to transfer the ɛ-amino group of N2-acetyllysine, a putative intermediate in lysine biosynthesis, to 2-oxoglutarate. When N2-acetylornithine, a substrate for arginine biosynthesis, was used as the substrate for the reaction, LysJ transferred the δ-amino group of N2-acetylornithine to 2-oxoglutarate 16 times more efficiently than when N2-acetyllysine was the amino donor. All these results suggest that lysine biosynthesis in T. thermophilus HB27 is functionally and evolutionarily related to arginine biosynthesis. PMID:11489859

  10. Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.

    Science.gov (United States)

    Bremang, Michael; Cuomo, Alessandro; Agresta, Anna Maria; Stugiewicz, Magdalena; Spadotto, Valeria; Bonaldi, Tiziana

    2013-09-01

    Protein methylation is a post-translational modification (PTM) by which a variable number of methyl groups are transferred to lysine and arginine residues within proteins. Despite increased interest in this modification due to its reversible nature and its emerging role in a diverse set of biological pathways beyond chromatin, global identification of protein methylation has remained an unachieved goal. To characterise sites of lysine and arginine methylation beyond histones, we employed an approach that combines heavy methyl stable isotope labelling by amino acids in cell culture (hmSILAC) with high-resolution mass spectrometry-based proteomics. Through a broad evaluation of immuno-affinity enrichment and the application of two classical protein separation techniques prior to mass spectrometry, to nucleosolic and cytosolic fractions separately, we identified a total of 501 different methylation types, on 397 distinct lysine and arginine sites, present on 139 unique proteins. Our results considerably extend the number of known in vivo methylation sites and indicate their significant presence on several protein complexes involved at all stages of gene expression, from chromatin remodelling and transcription to splicing and translation. In addition, we describe the potential of the hmSILAC approach for accurate relative quantification of methylation levels between distinct functional states.

  11. Acute hormonal response to glucose, lipids and arginine infusion