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Sample records for aminopropionic acid-beta

  1. Metabolic engineering of Escherichia coli for the production of 3-aminopropionic acid.

    Science.gov (United States)

    Song, Chan Woo; Lee, Joungmin; Ko, Yoo-Sung; Lee, Sang Yup

    2015-07-01

    A novel metabolic pathway was designed for the production of 3-aminopropionic acid (3-AP), an important platform chemical for manufacturing acrylamide and acrylonitrile. Using a fumaric acid producing Escherichia coli strain as a host, the Corynebacterium glutamicum panD gene (encoding L-aspartate-α-decarboxylase) was overexpressed and the native promoter of the aspA gene was replaced with the strong trc promoter, which allowed aspartic acid production through the aspartase-catalyzed reaction. Additional overexpression of aspA and ppc genes, and supplementation of ammonium sulfate in the medium allowed production of 3.49 g/L 3-AP. The 3-AP titer was further increased to 3.94 g/L by optimizing the expression level of PPC using synthetic promoters and RBS sequences. Finally, native promoter of the acs gene was replaced with strong trc promoter to reduce acetic acid accumulation. Fed-batch culture of the final strain allowed production of 32.3 g/L 3-AP in 39 h.

  2. Crystallization and Preliminary X-ray analysis of Human Recombinant Acid beta-glucocerebrosidase, a treatment for Gaucher's Disease

    Science.gov (United States)

    Roeber, Dana F.; Achari, Aniruddha; Manavalan, Partha; Edmunds, Tim; Scott, David L.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Acid beta-glucocerebrosidase (N-acylsphingosyl - O - beta-D - glucoside:glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme(R) (Genzyme Corporation, Cambridge, MA) is a partially deglycosylated form of recombinant human acid beta-glucocerebrosidase that is commercially available for the treatment of Gaucher patients. Although acid beta-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. We report the crystallization and the initial diffraction analysis of Cerezyme(R). The crystals are C-centered orthorhombic, with unit-cell parameters of a = 285.0 A, b = 110.2 A, and c = 91.7 A. A 99.9 A complete data set has been collected to 2.75 A with an R(sub sym) of 8.8 %.

  3. Crystallization and preliminary X-ray analysis of recombinant human acid beta-glucocerebrosidase, a treatment for Gaucher's disease

    Science.gov (United States)

    Roeber, Dana; Achari, Aniruddha; Manavalan, Partha; Edmunds, Tim; Scott, David L.

    2003-01-01

    Acid beta-glucocerebrosidase (N-acylsphingosyl-1-O-beta-D-glucoside:glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme (Genzyme Corporation, Cambridge, MA, USA) is a partially deglycosylated form of recombinant human acid beta-glucocerebrosidase that is used in the treatment of Gaucher patients. Although acid beta-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. Here, the crystallization and the initial diffraction analysis of Cerezyme are reported. The crystals are C-centered orthorhombic, with unit-cell parameters a = 285.0, b = 110.2, c = 91.7 A. A 99.9% complete data set has been collected to 2.75 A with an R(sym) of 8.8%.

  4. Poly (γ-glutamic acid)/beta-TCP nanocomposites via in situ copolymerization: Preparation and characterization.

    Science.gov (United States)

    Shu, Xiu-Lin; Shi, Qing-Shan; Feng, Jin; Yang, Yun-Hua; Zhou, Gang; Li, Wen-Ru

    2016-07-01

    A series biodegradable poly (γ-glutamic acid)/beta-tricalcium phosphate (γ-PGA/TCP) nanocomposites were prepared which were composed of poly-γ-glutamic acid polymerized in situ with β-tricalcium phosphate and physiochemically characterized as bone graft substitutes. The particle size via dynamic light scattering, the direct morphological characterization via transmission electron microscopy and field emission scanning electron microscope, which showed that γ-PGA and β-TCP were combined compactly at 80℃, and the γ-PGA/TCP nanocomposites had homogenous and nano-sized grains with narrow particle size distributions. The water uptake and retention abilities, in vitro degradation properties, cytotoxicity in the simulated medium, and protein release of these novel γ-PGA/TCP composites were investigated. Cell proliferation in composites was nearly twice than β-TCP when checked in vitro using MC3T3 cell line. We also envision the potential use of γ-PGA/TCP systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering applications. These observations suggest that the γ-PGA/TCP are novel nanocomposites with great potential for application in the field of bone tissue engineering.

  5. Quantification of syntrophic fatty acid-beta-oxidizing bacteria in a mesophilic biogas reactor by oligonucleotide probe hybridization

    DEFF Research Database (Denmark)

    Hansen, K.W.; Ahring, Birgitte Kiær; Raskin, L.

    1999-01-01

    Small-subunit rRNA sequences were obtained for two saturated fatty acid-beta-oxidizing syntrophic bacteria, Syntrophomonas sapovorans and Syntrophomonas wolfei LYE, and sequence analysis confirmed their classification as members of the family Syntrophomonadaceae. S, wolfei LYE was closely related...... to S. wolfei subsp. wolfei, but S. sapovorans did not cluster with the other members of the genus Syntrophomonas, Five oligonucleotide probes targeting the small-subunit rRNA of different groups within the family Syntrophomonadaceae, which contains all currently known saturated fatty acid...... fatty acid-beta-oxidizing syntrophic bacteria in methanogenic environments, the microbial community structure of a sample from a full-scale biogas plant was determined. Hybridization results with probes for syntrophic bacteria-and methanogens were compared to specific methanogenic activities...

  6. The fatty acid beta-oxidation pathway is important for decidualization of endometrial stromal cells in both humans and mice.

    Science.gov (United States)

    Tsai, Jui-He; Chi, Maggie M-Y; Schulte, Maureen B; Moley, Kelle H

    2014-02-01

    Embryo implantation and development requires the endometrial stromal cells (ESCs) to undergo decidualization. This differentiation process requires glucose utilization, and blockade of the pentose phosphate pathway inhibits decidualization of ESCs both in vitro and in vivo. Glucose and fatty acids are energy substrates for many cell types, and fatty acid beta-oxidation is critical for embryo implantation. Here, we investigated whether beta-oxidation is required for decidualization of ESCs. As assessed by marker gene expression, decidualization of human primary ESCs was blocked by reducing activity of carnitine calmitoyltransferase I, the rate-limiting enzyme in beta-oxidation, either by short hairpin RNA-mediated silencing or by treatment with the inhibitor etomoxir. Ranolazine (RAN), a partial beta-oxidation inhibitor, blocked early decidualization of a human ESC line. However, decidualization resumed after several days, most likely due to a compensatory up-regulation of GLUT1 expression and an increase in glucose metabolism. Simultaneous inhibition of the beta-oxidation pathway with RAN and the pentose phosphate pathway with glucosamine (GlcN) impaired in vitro decidualization of human ESCs more strongly than inhibition of either pathway alone. These findings were confirmed in murine ESCs in vitro, and exposure to RAN plus GlcN inhibited decidualization in vivo in a deciduoma model. Finally, intrauterine implantation of time-release RAN and GlcN pellets reduced pup number. Importantly, pup number returned to normal after the end of the pellet-active period. This work indicates that both fatty acids and glucose metabolism pathways are important for ESC decidualization, and suggests novel pathways to target for the design of future nonhormonal contraceptives.

  7. In vivo and ex vivo evaluation of L-type calcium channel blockers on acid beta-glucosidase in Gaucher disease mouse models.

    Directory of Open Access Journals (Sweden)

    Ying Sun

    Full Text Available Gaucher disease is a lysosomal storage disease caused by mutations in acid beta-glucosidase (GCase leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC blockers-verapamil and diltiazem-have been reported to modulate endoplasmic reticulum (ER folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT, V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50-200 mg/kg/d intraperitoneally had minor effects on increasing GCase activity in brain and liver (1.2-fold. Diltiazem treatment (10 mg/kg/d had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses.

  8. Properties of a fluorescent bezafibrate derivative (DNS-X). A new tool to study peroxisome proliferation and fatty acid beta-oxidation.

    Science.gov (United States)

    Berlot, J P; Lutz, T; Cherkaoui Malki, M; Nicolas-Frances, V; Jannin, B; Latruffe, N

    2000-12-01

    The first peroxisome proliferator-activated receptor (PPAR) was cloned in 1990 by Issemann and Green. Many studies have reported the importance of this receptor in the control of gene expression of enzymes involved in lipid metabolic pathways including mitochondrial and peroxisomal fatty acid beta-oxidation, lipoprotein structure [apolipoprotein (apo) A2, apo CIII], and fatty acid synthase. By using radiolabeled molecules, it was shown that peroxisome proliferators bind and activate PPAR. As an alternative method, we developed a fluorescent dansyl (1-dimethylaminonaphthalene-5-sulfonyl) derivative peroxisome proliferator from bezafibrate (DNS-X), a hypolipidemic agent that exhibits an in vitro peroxisome proliferative activity on rat Fao-hepatic derived cultured cells. However, until now, the effect of this new compound on the liver of animals and subcellular localization was unknown. In addition to in vivo rat studies, we present a more efficient large-scale technique of DNS-X purification. Treating rats (DNS-X in the diet at 0.3% w/w) for 6 d leads to a hepatomegaly and a marked increase in liver peroxisomal palmitoyl-CoA oxidase activity. We also developed a method to localize and quantify DNS-X in tissues or cell compartment organelles. The primarily cytosolic distribution of DNS-X was confirmed by direct visualization using fluorescence microscopy of cultured Fao cells. Finally, transfection assay demonstrated that DNS-X enhanced the PPAR alpha activity as well as other peroxisome proliferators do.

  9. Binding of 3,4,5,6-Tetrahydroxyazepanes to the Acid-[beta]-glucosidase Active Site: Implications for Pharmacological Chaperone Design for Gaucher Disease

    Energy Technology Data Exchange (ETDEWEB)

    Orwig, Susan D.; Tan, Yun Lei; Grimster, Neil P.; Yu, Zhanqian; Powers, Evan T.; Kelly, Jeffery W.; Lieberman, Raquel L. (Scripps); (GIT)

    2013-03-07

    Pharmacologic chaperoning is a therapeutic strategy being developed to improve the cellular folding and trafficking defects associated with Gaucher disease, a lysosomal storage disorder caused by point mutations in the gene encoding acid-{beta}-glucosidase (GCase). In this approach, small molecules bind to and stabilize mutant folded or nearly folded GCase in the endoplasmic reticulum (ER), increasing the concentration of folded, functional GCase trafficked to the lysosome where the mutant enzyme can hydrolyze the accumulated substrate. To date, the pharmacologic chaperone (PC) candidates that have been investigated largely have been active site-directed inhibitors of GCase, usually containing five- or six-membered rings, such as modified azasugars. Here we show that a seven-membered, nitrogen-containing heterocycle (3,4,5,6-tetrahydroxyazepane) scaffold is also promising for generating PCs for GCase. Crystal structures reveal that the core azepane stabilizes GCase in a variation of its proposed active conformation, whereas binding of an analogue with an N-linked hydroxyethyl tail stabilizes GCase in a conformation in which the active site is covered, also utilizing a loop conformation not seen previously. Although both compounds preferentially stabilize GCase to thermal denaturation at pH 7.4, reflective of the pH in the ER, only the core azepane, which is a mid-micromolar competitive inhibitor, elicits a modest increase in enzyme activity for the neuronopathic G202R and the non-neuronopathic N370S mutant GCase in an intact cell assay. Our results emphasize the importance of the conformational variability of the GCase active site in the design of competitive inhibitors as PCs for Gaucher disease.

  10. Gaucher disease: A G[sup +1][yields]A[sup +1] IVS2 splice donor site mutation causing exon 2 skipping in the acid [beta]-glucosidase mRNA

    Energy Technology Data Exchange (ETDEWEB)

    He, Guo-Shun (Mount Siani School of Medicine, New York, NY (United States)); Grabowski, G.A. (Children' s Hospital Medical Center, Cincinnati, OH (United States))

    1992-10-01

    Gaucher disease is the most frequent lysosomal storage disease and the most prevalent Jewish genetic disease. About 30 identified missense mutations are causal to the defective activity of acid [beta]-glucosidase in this disease. cDNAs were characterized from a moderately affected 9-year-old Ashkenazi Jewish Gaucher disease type 1 patient whose 80-years-old, enzyme-deficient, 1226G (Asn[sup 370][yields]Ser [N370S]) homozygous grandfather was nearly asymptomatic. Sequence analyses revealed four populations of cDNAs with either the 1226G mutation, an exact exon 2 ([Delta] EX2) deletion, a deletion of exon 2 and the first 115 bp of exon 3 ([Delta] EX2-3), or a completely normal sequence. About 50% of the cDNAs were the [Delta] EX2, the [Delta] EX2-3, and the normal cDNAs, in a ratio of 6:3:1. Specific amplification and characterization of exon 2 and 5[prime] and 3[prime] intronic flanking sequences from the structural gene demonstrated clones with either the normal sequence or with a G[sup +1][yields]A[sup +1] transition at the exon 2/intron 2 boundary. This mutation destroyed the splice donor consensus site (U1 binding site) for mRNA processing. This transition also was present at the corresponding exon/intron boundary of the highly homologous pseudogene. This new mutation, termed [open quotes]IVS2 G[sup +1],[close quotes] is the first in the Ashkenazi Jewish population. The occurrence of this [open quotes]pseudogene[close quotes]-type mutation in the structural gene indicates the role of acid [beta]-glucosidase pseudogene and structural gene rearrangements in the pathogenesis of this disease. 33 refs., 8 figs., 1 tab.

  11. Relationship between aged-rat brain fatty acid composition and fatty acid beta-oxidation%老年大鼠脑脂肪酸含量与脂肪酸β-氧化的关系

    Institute of Scientific and Technical Information of China (English)

    杨磊; 石如玲; 张煜; 赵春澎; 付云; 黄艳梅

    2011-01-01

    目的 比较老年及青年大鼠脑脂肪酸含量、肝脏脂肪酸β-氧化关键酶表达水平的不同,探讨衰老时脂肪酸含量的变化与脂肪酸β-氧化功能的关系.方法 老年组和青年组大鼠各10只,用气相色谱法分析脑皮质脂肪酸含量,用反转录聚合酶链反应(RT-PCR)方法测定过氧化物酶体β-氧化关键酶脂酰辅酶A氧化酶(AOX1)、线粒体β-氧化关键酶肉碱脂酰转移酶1( CPT1)及过氧化物酶体增殖剂激活受体α(PPARα) mRNA的表达水平,用游离脂肪酸试剂盒测定血清游离脂肪酸(FFA)含量.结果 与青年组相比,老年组大鼠脑内C18∶0、C20∶4、C22∶6含量降低(P<0.05或P<0.01),脑内C16∶1、C18∶1、C20∶0、C20∶1、C22∶1、C24∶0、C24∶1含量升高(P<0.05或P<0.01),肝脏AOX1、CPT1、PPARα mRNA水平降低(P<0.05),血清总FFA含量降低(P<0.05).结论 衰老时大鼠脑脂肪酸含量变化的原因可能由线粒体和过氧化物酶体β-氧化功能降低所致.%Objective To analyze the differences of brain fatty acid content and liver fatty acid beta-oxidation enzyme expression between aged and young rats, and to explore the relationship between aged brain fatty acid composition and fatty acid beta-oxidation. Methods Old (22 months) and young (3 months) male rats were used in this experiment. Every ten mice in old group and young group. Fatty acid composition and contents of cerebral cortex were detected by gas chromatography analysis. The mRNA levels of acyl-CoA oxidase 1 (AOX1) ,camitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-ac-tivated receptor-a (PPARa) in liver were detected by reverse transcription-polymerase chain reaction (RT-PCR). Serum free fatty acid (FFA) level was measured by the assay kit. Results Compared with the young group, C18 : 0.C20 : 4 and C22 : 6 levels decreased( P<0.05 or P<0.01), while C16 : 1.C18 : l,C20 :0,C20 : 1,C22 : 1,C24 : 0 and C24 : 1 levels increased (P< 0.05 orP<0

  12. Phylogenomic evidence for a myxococcal contribution to the mitochondrial fatty acid beta-oxidation.

    Directory of Open Access Journals (Sweden)

    Agatha Schlüter

    Full Text Available BACKGROUND: The origin of eukaryotes remains a fundamental question in evolutionary biology. Although it is clear that eukaryotic genomes are a chimeric combination of genes of eubacterial and archaebacterial ancestry, the specific ancestry of most eubacterial genes is still unknown. The growing availability of microbial genomes offers the possibility of analyzing the ancestry of eukaryotic genomes and testing previous hypotheses on their origins. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have applied a phylogenomic analysis to investigate a possible contribution of the Myxococcales to the first eukaryotes. We conducted a conservative pipeline with homologous sequence searches against a genomic sampling of 40 eukaryotic and 357 prokaryotic genomes. The phylogenetic reconstruction showed that several eukaryotic proteins traced to Myxococcales. Most of these proteins were associated with mitochondrial lipid intermediate pathways, particularly enzymes generating reducing equivalents with pivotal roles in fatty acid β-oxidation metabolism. Our data suggest that myxococcal species with the ability to oxidize fatty acids transferred several genes to eubacteria that eventually gave rise to the mitochondrial ancestor. Later, the eukaryotic nucleocytoplasmic lineage acquired those metabolic genes through endosymbiotic gene transfer. CONCLUSIONS/SIGNIFICANCE: Our results support a prokaryotic origin, different from α-proteobacteria, for several mitochondrial genes. Our data reinforce a fluid prokaryotic chromosome model in which the mitochondrion appears to be an important entry point for myxococcal genes to enter eukaryotes.

  13. Dynamic simulations on the mitochondrial fatty acid Beta-oxidation network

    Directory of Open Access Journals (Sweden)

    Weinberger Klaus M

    2009-01-01

    Full Text Available Abstract Background The oxidation of fatty acids in mitochondria plays an important role in energy metabolism and genetic disorders of this pathway may cause metabolic diseases. Enzyme deficiencies can block the metabolism at defined reactions in the mitochondrion and lead to accumulation of specific substrates causing severe clinical manifestations. Ten of the disorders directly affecting mitochondrial fatty acid oxidation have been well-defined, implicating episodic hypoketotic hypoglycemia provoked by catabolic stress, multiple organ failure, muscle weakness, or hypertrophic cardiomyopathy. Additionally, syndromes of severe maternal illness (HELLP syndrome and AFLP have been associated with pregnancies carrying a fetus affected by fatty acid oxidation deficiencies. However, little is known about fatty acids kinetics, especially during fasting or exercise when the demand for fatty acid oxidation is increased (catabolic stress. Results A computational kinetic network of 64 reactions with 91 compounds and 301 parameters was constructed to study dynamic properties of mitochondrial fatty acid β-oxidation. Various deficiencies of acyl-CoA dehydrogenase were simulated and verified with measured concentrations of indicative metabolites of screened newborns in Middle Europe and South Australia. The simulated accumulation of specific acyl-CoAs according to the investigated enzyme deficiencies are in agreement with experimental data and findings in literature. Investigation of the dynamic properties of the fatty acid β-oxidation reveals that the formation of acetyl-CoA – substrate for energy production – is highly impaired within the first hours of fasting corresponding to the rapid progress to coma within 1–2 hours. LCAD deficiency exhibits the highest accumulation of fatty acids along with marked increase of these substrates during catabolic stress and the lowest production rate of acetyl-CoA. These findings might confirm gestational loss to be the explanation that no human cases of LCAD deficiency have been described. Conclusion In summary, this work provides a detailed kinetic model of mitochondrial metabolism with specific focus on fatty acid β-oxidation to simulate and predict the dynamic response of that metabolic network in the context of human disease. Our findings offer insight into the disease process (e.g. rapid progress to coma and might confirm new explanations (no human cases of LCAD deficiency, which can hardly be obtained from experimental data alone.

  14. Profiling the Changes in Signaling Pathways in Ascorbic Acid/beta-Glycerophosphate-Induced Osteoblastic Differentiation

    NARCIS (Netherlands)

    Chaves Neto, Antonio Hernandes; Queiroz, Karla Cristiana; Milani, Renato; Paredes-Gamero, Edgar Julian; Justo, Giselle Zenker; Peppelenbosch, Maikel P.; Ferreira, Carmen Verissima

    2011-01-01

    Despite numerous reports on the ability of ascorbic acid and beta-glycerophosphate (AA/beta-GP) to induce osteoblast differentiation, little is known about the molecular mechanisms involved in this phenomenon. In this work, we used a peptide array containing specific consensus sequences (potential s

  15. 蚊虫驱避剂驱蚊酯的合成及应用%Synthesis and Application of Mosquito Repellent 3-[N-butyl-N-acetyl]-aminopropionic Acid, Ethyl Ester

    Institute of Scientific and Technical Information of China (English)

    危利红; 董琳; 王玉洁; 刘林森; 李昌杰

    2014-01-01

    以丙烯酸乙酯、正丁胺、乙酰氯为原料制备驱蚊酯,收率85%,纯度99.6%;其结构经红外光谱确证;按照GB/T17322.10-1998对产品的驱蚊效果进行了检测,效果理想.

  16. Synthesis and antitumor activity of camptothecin-20-O-β-aminopropionates%喜树碱20-O-β-胺基丙酸酯类衍生物的合成及抗肿瘤活性

    Institute of Scientific and Technical Information of China (English)

    李玉艳; 尤启冬; 陈晟; 王磊; 陈晓光; 李燕; 李洪燕

    2009-01-01

    目的:研究Topo Ⅰ抑制剂喜树碱β-胺基酸酯类衍生物的合成、抗肿瘤活性和血液稳定性,寻找高效低毒的肿瘤治疗药物.方法:通过喜树碱、9-硝基喜树碱和7-乙基喜树碱的20位羟基与丙烯酰氯反应得化合物1a~3a,然后与仲胺进行Michael加成,产物与盐酸成盐分别制得目标化合物1b~1e,2b~2e,3b~3e.采用MTT法对上述化合物进行4个瘤株KB,HT-29,HCT-8,Bel 7402的抗肿瘤活性测定.以化合物1b和1e为代表检测了目标化合物在人血液中的稳定性.结果:合成了12个新的化合物,其结构经IR、1H NMR、MS等确证.所有目标化合物都有较好的抗肿瘤活性,其中7个化合物1b,3b,1c,3c,3d,2e和3e的抗肿瘤活性强于羟基喜树碱,化合物1c,3b和3d的抗肿瘤活性与喜树碱相当.与喜树碱相比,化合物1b和1e的血液稳定性从5.2%增加到66.6%和55.1%.结论:Topo Ⅰ抑制剂喜树碱β-氨基酸酯类衍生物有较好的抗肿瘤活性,20位成酯增加在血液中的稳定性,且有利于降低毒性.化合物1c,3b和3d的活性较强,值得进一步研究.

  17. Acid-beta-glycerophosphatase reaction products in the central nervous system mitochondria following x-ray irradiation.

    Science.gov (United States)

    Roizin, L; Orlovskaja, D; Liu, J C; Carsten, A L

    1975-06-01

    A survey of the literature to date on the enzyme histochemistry of intracellular organelles has not yielded any reference to the presence of acid phosphatase reaction products in the mammalian mitochondria of the central nervous system. A combination of Gomori's acid phosphatase mehtod, however, with standard electron microscopy has disclosed the presence of enzyme reaction products in the mitochondria of the central nervous system of rats from 2 hr to 22 weeks after x-ray irradiation, as well as in a cerebral biopsy performed on a patient affected by Huntington's chorea. No enzyme reaction products, on the other hand, were observed in serial sections that had been incubated in substrates either containing sodium fluoride or lacking in beta-glycerophosphate. The abnormal mitochondrial enzyme reaction (chemical lesion) is considered to be the consequenco of the pathologic process affecting the ultrastructural-chemical organization of the organelle.

  18. Ascorbic acid Beta-Carotene and Amino acids in Capsicum (Capsicum annuum during fruit development in Himalayan Hills

    Directory of Open Access Journals (Sweden)

    P. C. Pant

    1984-04-01

    Full Text Available Capsicum varieties viz HC-201 & HC-202 developed at ARU, Almora took 35 days from fruit set to ripening. Results showed significant positive correlation for ascorbic acid and Beta-carotene with days to maturity. Out of eight ninhydrin positive products, only seven could be identified viz, hydroxyproline, proline, lysine, 5-alanine, arginine, threonine and methionine, at the later stages of the fruit development. All amino acids except methionine were found either absent or in traces at the earlier stages of fruit development.

  19. Genetic defects in fatty acid beta-oxidation and acyl-CoA dehydrogenases. Molecular pathogenesis and genotype-phenotype relationships

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter; Andresen, Brage S

    2004-01-01

    , stability and kinetic properties for this variant enzyme will be discussed in detail and used as a paradigm for the study of other mis-sense variant proteins. We conclude that the total effect of mis-sense sequence variations may comprise an invariable--sequence variation specific--effect on the catalytic...... parameters and a conditional effect, which is dependent on cellular, physiological and genetic factors other than the sequence variation itself....

  20. The cycad neurotoxic amino acid, beta-N-methylamino-L-alanine (BMAA), elevates intracellular calcium levels in dissociated rat brain cells.

    Science.gov (United States)

    Brownson, Delia M; Mabry, Tom J; Leslie, Steven W

    2002-10-01

    Seeds of the Guam cycad Cycas micronesica K.D. Hill (Cycadaceae), which contain ss-methylamino-L-alanine (BMAA), have been implicated in the etiology of the devastating neurodisease ALS-PDC that is found among the native Chamorros on Guam. The disease also occurs in the native populations on Irian Jaya and the Kii Peninsula of Japan, and in all three areas the cycad seeds are used either dietarily or medically. ALS-PDC is a complex of amyotrophic lateral sclerosis and parkinsonism dementia complex with additional symptoms of Alzheimer's. It is well known that Ca(2+) elevations in brain cells can lead to cell death and neurodiseases. Therefore, we evaluated the ability of the cycad toxin BMAA to elevate the intracellular calcium concentration ([Ca(2+)](i)) in dissociated newborn rat brain cells loaded with fura-2 dye. BMAA produced an increase in intracellular calcium levels in a concentration-dependent manner. The increases were dependent not only on extracellular calcium concentrations, but also significantly on the presence of bicarbonate ion. Increasing concentrations of sodium bicarbonate resulted in a potentiation of the BMAA-induced [Ca(2+)](i) elevation. The bicarbonate dependence did not result from the increased sodium concentration or alkalinization of the buffer. Our results support the hypothesis that the neurotoxicity of BMAA is due to an excitotoxic mechanism, involving elevated intracellular calcium levels and bicarbonate. Furthermore, since BMAA alone produced no increase in Ca(2+) levels, these results suggest the involvement of a product of BMAA and CO(2), namely a beta-carbamate, which has a structure similar to other excitatory amino acids (EAA) such as glutamate; thus, the causative agent for ALS-PDC on Guam and elsewhere may be the beta-carbamate of BMAA. These findings support the theory that some forms of other neurodiseases may also involve environmental toxins.

  1. Importance of the Long-Chain Fatty Acid Beta-Hydroxylating Cytochrome P450 Enzyme YbdT for Lipopeptide Biosynthesis in Bacillus subtilis Strain OKB105

    Science.gov (United States)

    Youssef, Noha H.; Wofford, Neil; McInerney, Michael J.

    2011-01-01

    Bacillus species produce extracellular, surface-active lipopeptides such as surfactin that have wide applications in industry and medicine. The steps involved in the synthesis of 3-hydroxyacyl-coenzyme A (CoA) substrates needed for surfactin biosynthesis are not understood. Cell-free extracts of Bacillus subtilis strain OKB105 synthesized lipopeptide biosurfactants in presence of l-amino acids, myristic acid, coenzyme A, ATP, and H2O2, which suggested that 3-hydroxylation occurs prior to CoA ligation of the long chain fatty acids (LCFAs). We hypothesized that YbdT, a cytochrome P450 enzyme known to beta-hydroxylate LCFAs, functions to form 3-hydroxy fatty acids for lipopeptide biosynthesis. An in-frame mutation of ybdT was constructed and the resulting mutant strain (NHY1) produced predominantly non-hydroxylated lipopeptide with diminished biosurfactant and beta-hemolytic activities. Mass spectrometry showed that 95.6% of the fatty acids in the NHY1 biosurfactant were non-hydroxylated compared to only ∼61% in the OKB105 biosurfactant. Cell-free extracts of the NHY1 synthesized surfactin containing 3-hydroxymyristic acid from 3-hydroxymyristoyl-CoA at a specific activity similar to that of the wild type (17 ± 2 versus 17.4 ± 6 ng biosurfactant min−1·ng·protein−1, respectively). These results showed that the mutation did not affect any function needed to synthesize surfactin once the 3-hydroxyacyl-CoA substrate was formed and that YbdT functions to supply 3-hydroxy fatty acid for surfactin biosynthesis. The fact that YbdT is a peroxidase could explain why biosurfactant production is rarely observed in anaerobically grown Bacillus species. Manipulation of LCFA specificity of YbdT could provide a new route to produce biosurfactants with activities tailored to specific functions. PMID:21673922

  2. [The effect of fenofibrate on expression of genes involved in fatty acids beta-oxidation and associated free-radical processes].

    Science.gov (United States)

    Gureev, A P; Shmatkova, M L; Bashmakov, V Yu; Starkov, A A; Popov, V N

    2016-05-01

    Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b-oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria. Enhancement of oxidative processes caused a 2-fold increase in the rate of reactive oxygen species (ROS) production, as evidenced by determination of the level of lipid peroxidation (LPO) products in the liver. Mitochondrial antioxidant systems are more sensitive to elevated ROS production, as they respond by increased expression of SOD2 and PRDX3 genes, than cytoplasmic and peroxisomal antioxidant systems, where expression of CAT1, SOD1, PRDX5 genes remained unaltered.

  3. The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results.

    Science.gov (United States)

    Wanders, Ronald J A; Ruiter, Jos P N; IJLst, Lodewijk; Waterham, Hans R; Houten, Sander M

    2010-10-01

    Oxidation of fatty acids in mitochondria is a key physiological process in higher eukaryotes including humans. The importance of the mitochondrial beta-oxidation system in humans is exemplified by the existence of a group of genetic diseases in man caused by an impairment in the mitochondrial oxidation of fatty acids. Identification of patients with a defect in mitochondrial beta-oxidation has long remained notoriously difficult, but the introduction of tandem-mass spectrometry in laboratories for genetic metabolic diseases has revolutionalized the field by allowing the rapid and sensitive analysis of acylcarnitines. Equally important is that much progress has been made with respect to the development of specific enzyme assays to identify the enzyme defect in patients subsequently followed by genetic analysis. In this review, we will describe the current state of knowledge in the field of fatty acid oxidation enzymology and its application to the follow-up analysis of positive neonatal screening results.

  4. Importance of the Long-Chain Fatty Acid Beta-Hydroxylating Cytochrome P450 Enzyme YbdT for Lipopeptide Biosynthesis in Bacillus subtilis Strain OKB105

    Directory of Open Access Journals (Sweden)

    Michael J. McInerney

    2011-03-01

    Full Text Available Bacillus species produce extracellular, surface-active lipopeptides such as surfactin that have wide applications in industry and medicine. The steps involved in the synthesis of 3-hydroxyacyl-coenzyme A (CoA substrates needed for surfactin biosynthesis are not understood. Cell-free extracts of Bacillus subtilis strain OKB105 synthesized lipopeptide biosurfactants in presence of L-amino acids, myristic acid, coenzyme A, ATP, and H2O2, which suggested that 3-hydroxylation occurs prior to CoA ligation of the long chain fatty acids (LCFAs. We hypothesized that YbdT, a cytochrome P450 enzyme known to beta-hydroxylate LCFAs, functions to form 3-hydroxy fatty acids for lipopeptide biosynthesis. An in-frame mutation of ybdT was constructed and the resulting mutant strain (NHY1 produced predominantly non-hydroxylated lipopeptide with diminished biosurfactant and beta-hemolytic activities. Mass spectrometry showed that 95.6% of the fatty acids in the NHY1 biosurfactant were non-hydroxylated compared to only ~61% in the OKB105 biosurfactant. Cell-free extracts of the NHY1 synthesized surfactin containing 3-hydroxymyristic acid from 3-hydroxymyristoyl-CoA at a specific activity similar to that of the wild type (17 ± 2 versus 17.4 ± 6 ng biosurfactant min−1·ng·protein−1, respectively. These results showed that the mutation did not affect any function needed to synthesize surfactin once the 3-hydroxyacyl-CoA substrate was formed and that YbdT functions to supply 3-hydroxy fatty acid for surfactin biosynthesis. The fact that YbdT is a peroxidase could explain why biosurfactant production is rarely observed in anaerobically grown Bacillus species. Manipulation of LCFA specificity of YbdT could provide a new route to produce biosurfactants with activities tailored to specific functions.

  5. Peroxisomal very long-chain fatty acid [beta]-oxidation in human skin fibroblasts: activity in Zellweger syndrome and other peroxisomal disorders

    NARCIS (Netherlands)

    Wanders, R.J.A.; Roermund, C.W.T. van; Wijland, M.J.A. van; Heikoop, J.; Schutgens, R.B.H.; Schram, A.W.; Tager, J.M.; Bosch, H. van den; Poll-Thé, B.T.; Saudubray, J.M.; Moser, H.W.; Moser, A.B.

    1987-01-01

    Since very long-chain fatty acids with a chain length of 24 carbons or more are known to accumulate in tissues and body fluids from patients with the cerebro-hepato-renal (Zellweger) syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and X-linked adrenoleukodystrophy, we studied very

  6. Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet.

    Directory of Open Access Journals (Sweden)

    Gaetano Serviddio

    Full Text Available There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH. The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I, the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.

  7. EST Table: DC548736 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available milar to Glucosylceramidase precursor (Beta-glucocerebrosidase) (Acid beta-glucosidase) (D-glucosyl-N-acylsp...ucosylceramidase precursor (Beta-glucocerebrosidase) (Acid beta-glucosidase) (D-g....1| PREDICTED: similar to Glucosylceramidase precursor (Beta-glucocerebrosidase) (Acid beta-glucosidase) (D-

  8. Triangular prism-shaped β-peptoid helices as unique biomimetic scaffolds

    DEFF Research Database (Denmark)

    Laursen, Jonas Striegler; Harris, Pernille; Fristrup, Peter;

    2015-01-01

    β-Peptoids are peptidomimetics based on N-alkylated β-aminopropionic acid residues (or N-alkyl-β-alanines). This type of peptide mimic has previously been incorporated in biologically active ligands and has been hypothesized to be able to exhibit foldamer properties. Here we show, for the first...... time, that β-peptoids can be tuned to fold into stable helical structures. We provide high-resolution X-ray crystal structures of homomeric β-peptoid hexamers, which reveal right-handed helical conformations with exactly three residues per turn and a helical pitch of 9.6-9.8 Å between turns...

  9. Inhibition of ultraviolet B (UVB) induced apoptosis in A431 cells by mimosine is not dependent on cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Cliche, D.O.; Girouard, S.; Bissonnette, N.; Hunting, D.J. [CIHR Group in the Radiation Sciences, Faculte de Medecine, Univ. de Sherbrooke, Sherbrooke, Quebec (Canada)

    2002-07-01

    Ultraviolet (UV) radiation is a strong apoptotic trigger in many cell types. We have. previously reported that a plant amino acid, mimosine ({beta}-[N-(3-hydroxy-4-pyridone)]-{alpha}-aminopropionic acid), with a well-known reversible G1 cell cycle arrest activity can inhibit apoptosis induced by UV irradiation and RNA polymerase II blockage in human A431 cells. Here, apoptosis was measured with a fluorimetric caspase activation assay. Interestingly, the protective state was effective up to 24 h following removal of mimosine from the culture medium while cells were progressing in the cell cycle. Our results demonstrate that the protective effect of mimosine against UV-induced apoptosis can be dissociated from its G1 cell-cycle arrest activity. (author)

  10. Effects of mimosine on Wolbachia in mosquito cells: cell cycle suppression reduces bacterial abundance.

    Science.gov (United States)

    Fallon, Ann M

    2015-10-01

    The plant allelochemical L-mimosine (β-[N-(3-hydroxy-4-pyridone)]-α-aminopropionic acid; leucenol) resembles the nonessential amino acid, tyrosine. Because the obligate intracellular alphaproteobacterium, Wolbachia pipientis, metabolizes amino acids derived from host cells, the effects of mimosine on infected and uninfected mosquito cells were investigated. The EC50 for mimosine was 6-7 μM with Aedes albopictus C7-10 and C/wStr cell lines, and was not influenced by infection status. Mosquito cells responded to concentrations of mimosine substantially lower than those used to synchronize the mammalian cell cycle; at concentrations of 30-35 μM, mimosine reversibly arrested the mosquito cell cycle at the G1/S boundary and inhibited growth of Wolbachia strain wStr. Although lower concentrations of mimosine slightly increased wStr abundance, concentrations that suppressed the cell cycle reduced Wolbachia levels.

  11. Secondary metabolites from the sponge Tedania anhelans: Isolation and characterization of two novel pyrazole acids and other metabolites

    Digital Repository Service at National Institute of Oceanography (India)

    Parameswaran, P; Naik, C.G.; Hegde, V.R.

    as natural products. The other compounds isolated were p-hydroxybenzaldehyde, phenylacetamide, 3-phenylpropionic acid, 3-(p-hydroxyphenyl) propionic acid, 3-(p-methoxyphenyl) propionic acid beta -carboline (norharman) (1), and the four diketopiperazines pro...

  12. AcEST: DK962771 [AcEST

    Lifescience Database Archive (English)

    Full Text Available TN Threonine aldolase OS=Thermoanaerobacter ... 199 2e-49 tr|B7R6Z2|B7R6Z2_9THEO Beta-eliminating lyase supe...|B0K216|B0K216_THEPX Aromatic amino acid beta-eliminating lyas... 196 1e-48 tr|B0KDB4|B0KDB4_THEP3 Aromatic amino acid beta-eliminati...ng lyas... 195 2e-48 tr|Q9K7S6|Q9K7S6_BACHD L-allo-threo

  13. The Chemistry and Biological Activities of Mimosine: A Review.

    Science.gov (United States)

    Nguyen, Binh Cao Quan; Tawata, Shinkichi

    2016-08-01

    Mimosine [β-[N-(3-hydroxy-4-oxypyridyl)]-α-aminopropionic acid] is a non-protein amino acid found in the members of Mimosoideae family. There are a considerable number of reports available on the chemistry, methods for estimation, biosynthesis, regulation, and degradation of this secondary metabolite. On the other hand, over the past years of active research, mimosine has been found to have various biological activities such as anti-cancer, antiinflammation, anti-fibrosis, anti-influenza, anti-virus, herbicidal and insecticidal activities, and others. Mimosine is a leading compound of interest for use in the development of RAC/CDC42-activated kinase 1 (PAK1)-specific inhibitors for the treatment of various diseases/disorders, because PAK1 is not essential for the growth of normal cells. Interestingly, the new roles of mimosine in malignant glioma treatment, regenerative dentistry, and phytoremediation are being emerged. These identified properties indicate an exciting future for this amino acid. The present review is focused on the chemistry and recognized biological activities of mimosine in an attempt to draw a link between these two characteristics. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Repellent efficacy of DEET, Icaridin, and EBAAP against Ixodes ricinus and Ixodes scapularis nymphs (Acari, Ixodidae).

    Science.gov (United States)

    Büchel, Kerstin; Bendin, Juliane; Gharbi, Amina; Rahlenbeck, Sibylle; Dautel, Hans

    2015-06-01

    Repellent efficacy of 10% EBAAP (3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester) and 10% Icaridin ((2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester)) were evaluated against 20% DEET (N,N-diethyl-3-methylbenzamide) in human subject trials against ticks. Responses of host-seeking nymphs of the European castor bean tick (Ixodes ricinus L.; Acari: Ixodidae) and the North American blacklegged tick (I. scapularis Say; Acari: Ixodidae) were compared. Tests were carried out according to the US-EPA standard protocol with ethanolic solutions of the active ingredients of repellents being applied to the forearm of 10 volunteers. The upward movement of ticks was monitored until repellent failure taking up to 12.5 h. Application of 20% DEET resulted in median complete protection times (CPT; Kaplan-Meier median) between 4 and 4.5 h, while 10% EBAAP yielded CPTs of 3.5-4h. No significant differences were found between the efficacies of two repellents nor between the two species tested. The median of the CPT of a 10% Icaridin solution was 5h in nymphs of I. scapularis, but 8h in those of I. ricinus (Prepellent activity against nymphs of the two Ixodes ticks with Icaridin demonstrating particularly promising results against I. ricinus. Future research should investigate whether similar results occur when adult Ixodes ticks or other tick species are tested.

  15. Infodisruption of inducible anti-predator defenses through commercial insect repellents?

    Science.gov (United States)

    von Elert, Eric; Preuss, Katja; Fink, Patrick

    2016-03-01

    Commercial insect repellents like DEET (N,N-diethyl-m-toluamide), EBAAP (IR3535(®), (3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester)) or Icaridine (picaridin, Bayrepel, 1-piperidinecarboxylic acid, 2-(2-hydroxyethyl), 1-methylpropyl ester) are used worldwide to protect against biting insects and ticks. The detection of these repellents in surface waters in concentrations up to several μg/L levels has caused concern that these substances might affect non-target organisms in freshwaters. Daphnia sp., a keystone organism in lakes and ponds, is known for diel vertical migration (DVM) and life-history changes (LHCs) as inducible defenses against predation by fish. Here we test whether (i) environmentally relevant concentrations of DEET, EBAPP or Icaridine have repellent effects on Daphnia magna and (ii) if these repellents are infodisruptors for DVM and LHCs. Using concentrations of up to 44 μg/L, the repellents neither had effects on juvenile somatic growth nor on clutch size. In thermally stratified water columns with a repellent-free hypolimnion, no repellent effects of the test compounds on D. magna were observed. The presence of fish-born infochemicals induced LHCs, which are characterized by a reduced size at first reproduction, and DVM in D. magna. These effects were not affected by the presence of either repellent. Hence no evidences for infodisruption of the chemical communication of fish and Daphnia by DEET, EBAAP or Icaridine were found.

  16. Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity

    DEFF Research Database (Denmark)

    Andersen, G; Wegner, L; Yanagisawa, K

    2005-01-01

    Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1......alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation, and hepatic gluconeogenesis....

  17. EST Table: FS840242 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available l|Amel|GB10584-PA 10/09/10 47 %/128 aa gi|91087383|ref|XP_975651.1| PREDICTED: similar to Glucosylceramidase precursor (Beta-glucocer...ebrosidase) (Acid beta-glucosidase) (D-glucosyl-N-acylsphingosine glucohydrolase) [Tribolium castaneum] FS796494 fner ...

  18. Synthesis of a tetrasaccharide fragment of hyaluronic acid having a glucuronic acid at the reducing end

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Slaghek, T.M.; Hyppönen, T.K.; Ogawa, T.; Kamerling, J.P.

    1993-01-01

    A stereocontrolled synthesis of a tetrasaccharide fragment of hyaluronic acid, beta-p-methoxyphenyl glycoside of beta-D-GlcNAc-(1¨4)-beta-D-GlcNAc-(1¨3)-beta-D-GlcNAc-(1¨4)-D-GlcA, is presented.

  19. Carnitine-dependent transport of acetyl coenzyme A in Candida albicans is essential for growth on nonfermentable carbon sources and contributes to biofilm formation

    NARCIS (Netherlands)

    Strijbis, Karin; van Roermund, Carlo W. T.; Visser, Wouter F.; Mol, Els C.; van den Burg, Janny; MacCallum, Donna M.; Odds, Frank C.; Paramonova, Ekaterina; Krom, Bastiaan P.; Distel, Ben

    2008-01-01

    In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid beta-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate

  20. Protein (Cyanobacteria): 190006 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06307237.1 1117:3784 1161:1065 1162:185 77021:737 77022:737 533240:737 Aromatic amino acid beta-eliminati...ng lyase/threonine aldolase Cylindrospermopsis raciborskii CS-505 MQIYLDYSATTPTRPEA

  1. Sequence Classification: 254890 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|71906303|ref|YP_283890.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase:Aminotransferase, class I and II || http://www.ncbi.nlm.nih.gov/protein/71906303 ...

  2. Protein (Cyanobacteria): 190018 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_01628438.1 1117:3784 1161:1065 1162:185 159191:587 70799:587 313624:587 Aromatic amino acid beta-eliminat...ing lyase/threonine aldolase Nodularia spumigena CCY9414 MSIIYLDNNATTKVDPEVLEAMLPYL

  3. Sequence Classification: 67600 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|75909050|ref|YP_323346.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/75909050 ...

  4. Protein (Cyanobacteria): 118161 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06309882.1 1117:2318 1161:1932 1162:2207 77021:2257 77022:2257 533240:2257 Aromatic amino acid beta-elimi...nating lyase/threonine aldolase Cylindrospermopsis raciborskii CS-505 MVANPTYRQISTE

  5. Protein (Cyanobacteria): 190016 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_01628991.1 1117:3784 1161:1065 1162:185 159191:587 70799:587 313624:587 Aromatic amino acid beta-eliminat...ing lyase/threonine aldolase Nodularia spumigena CCY9414 MQIYLDYSATTPTRPEAIAAIQTVLN

  6. Sequence Classification: 65212 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|75906662|ref|YP_320958.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/75906662 ...

  7. Protein (Cyanobacteria): 190017 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_01629460.1 1117:3784 1161:1065 1162:185 159191:587 70799:587 313624:587 Aromatic amino acid beta-eliminat...ing lyase/threonine aldolase Nodularia spumigena CCY9414 MSIRPIYLDGHATTPVDERVLAAMIP

  8. Sequence Classification: 68993 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|75910443|ref|YP_324739.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/75910443 ...

  9. Protein (Cyanobacteria): 190008 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06309414.1 1117:3784 1161:1065 1162:185 77021:737 77022:737 533240:737 Aromatic amino acid beta-eliminati...ng lyase/threonine aldolase Cylindrospermopsis raciborskii CS-505 MSEMLKNCIYLDNNATT

  10. Sequence Classification: 67524 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|75908974|ref|YP_323270.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/75908974 ...

  11. Sequence Classification: 465954 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|72383087|ref|YP_292442.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/72383087 ...

  12. Sequence Classification: 69701 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|75911151|ref|YP_325447.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/75911151 ...

  13. Protein (Cyanobacteria): 190009 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06304476.1 1117:3784 1161:1065 1162:185 244599:857 668331:857 533247:857 Aromatic amino acid beta-elimina...ting lyase/threonine aldolase Raphidiopsis brookii D9 MSIRPIYLDSHATTPLDERVLNAMIPYFT

  14. Protein (Cyanobacteria): 118162 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06304180.1 1117:2318 1161:1932 1162:2207 244599:657 668331:657 533247:657 Aromatic amino acid beta-elimin...ating lyase/threonine aldolase Raphidiopsis brookii D9 MVANPTYRQISTETTPSLGEFVRRHIGP

  15. Protein (Cyanobacteria): 190007 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06309064.1 1117:3784 1161:1065 1162:185 77021:737 77022:737 533240:737 Aromatic amino acid beta-eliminati...ng lyase/threonine aldolase Cylindrospermopsis raciborskii CS-505 MSIRPIYLDSHATTPLD

  16. Sequence Classification: 68668 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|75910118|ref|YP_324414.1| Aromatic amino acid beta-elimi...nating lyase/threonine aldolase || http://www.ncbi.nlm.nih.gov/protein/75910118 ...

  17. Protein (Cyanobacteria): 132359 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available YP_001865079.1 1117:2589 1161:2767 1162:3127 1177:2248 272131:1413 63737:1413 aromatic amino acid beta-elimi...nating lyase/threonine aldolase Nostoc punctiforme PCC 73102 MSSNLEQFASDNSSGICPEALE

  18. Protein (Cyanobacteria): 190010 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ZP_06305932.1 1117:3784 1161:1065 1162:185 244599:857 668331:857 533247:857 Aromatic amino acid beta-elimina...ting lyase/threonine aldolase Raphidiopsis brookii D9 MCYYKTTQHFPPTNNANAMQIYLDYSATT

  19. Disease: H00123 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ransplantation Chemical chaperone therapy; N-octyl-4-epi-beta-valienamine (NOEV) ...i Y Chemical chaperone therapy for GM1-gangliosidosis. Cell Mol Life Sci 65:351-3 (2008) ... ...ons affecting the catalytic site of acid beta-galactosidase. Hum Mutat 30:1214-21 (2009) PMID:18202827 Suzuk

  20. SwissProt search result: AK071889 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071889 J013047P08 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 4e-37 ...

  1. SwissProt search result: AK101250 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101250 J033032E23 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 9e-30 ...

  2. SwissProt search result: AK121115 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121115 J023073M23 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 4e-49 ...

  3. SwissProt search result: AK063953 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK063953 001-123-F10 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 3e-69 ...

  4. SwissProt search result: AK105972 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105972 001-205-F03 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 1e-67 ...

  5. SwissProt search result: AK102185 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102185 J033086N13 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 4e-51 ...

  6. SwissProt search result: AK073663 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073663 J033046A21 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 5e-53 ...

  7. SwissProt search result: AK058571 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK058571 001-017-E08 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 8e-52 ...

  8. SwissProt search result: AK119902 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119902 002-181-D04 (Q01412) Glucan endo-1,3-beta-glucosidase A precursor (EC 3.2.1.39) ((1->3)-beta-gluca...n endohydrolase A) ((1->3)-beta-glucanase A) (Acidic beta-1,3-glucanase) (Beta-1,3-endoglucanase A) E13A_LYCES 4e-72 ...

  9. Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men

    DEFF Research Database (Denmark)

    Ribel-Madsen, Amalie; Ribel-Madsen, Rasmus; Brøns, Charlotte;

    2016-01-01

    measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5‐day high‐fat, high‐calorie diet. We demonstrated that LBW men had higher C2 and C4‐OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta...

  10. Isolation of octapeptin D (studies on antibiotics from the genus Bacillus. XXVII).

    Science.gov (United States)

    Shoji, J; Sakazaki, R; Wakisaka, Y; Koizumi, K; Matsuura, S; Miwa, H; Mayama, M

    1980-02-01

    A new peptide antibiotic complex, named octapeptin D, was isolated from culture broth of a microorganism belonging to the genus Bacillus. The trihydrochloride of the antibiotic was obtained as a colorless powder, soluble in water and methanol. The empirical formula, C47H88N12O11.3HCl.H2O, was indicated by elemental analysis. Amino acid analysis on the acid hydrolyzate demonstrated the presence of 2,4-diaminobutyric acid (4 moles), serine (1 mole) and leucine (3 moles). Gas chromatographic analysis with the methylated product of the ethereal extract of the acid hydrolyzate revealed the presence of beta-hydroxy isodecanoic acid, beta-hydroxy decanoic acid, beta-hydroxy isoundecanoic acid and beta-hydroxyanteisoundecanoic acid. Octapeptin D is active against Gram-negative and Gram-positive bacteria in vitro and in vivo.

  11. Unusual fatty acid substitution in lipids and lipopolysaccharides of Helicobacter pylori.

    OpenAIRE

    Geis, G; Leying, H; Suerbaum, S; Opferkuch, W

    1990-01-01

    Cellular fatty acids, phospholipid fatty acids, and lipopolysaccharide fatty acids of four strains of Helicobacter pylori were analyzed by gas-liquid chromatography. The presence of myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, 19-carbon cyclopropane fatty acid, beta-hydroxypalmitic acid, and beta-hydroxystearic acid was confirmed. In phospholipids, myristic acid and 19-carbon cyclopropane fatty acid were the major fatty acids. Hydroxy fatty acids and unsaturated fatt...

  12. Bioactive phytochemicals and antioxidant activity in fresh and dried lychee fractions1

    OpenAIRE

    2015-01-01

    Fruit of the lychee cv. Bengal are approximately 50% peel and seeds, which are discarded. These by-products have antioxidant compounds which are capable of blocking the harmful effects of free radicals in the body. Bioactive compounds (ascorbic acid, beta-carotene, lycopene and phenols) and antioxidant activity were evaluated in different extracts, both fresh and dried at 45 °C, of the skin, pulp and seeds of the lychee, which were subjected to principal component analysis to clarify which of...

  13. Hydrophobic Zeolites for Applications in Adsorption and Catalysis

    OpenAIRE

    Huang, Zige; Cordon, Michael; Gounder, Rajamani

    2016-01-01

    Lewis acidic zeolites such as Sn-Beta are commonly studied for use as selective catalysts for glucose isomerization to fructose in liquid water. Glucose to fructose isomerization is a critical reaction for lignocellulosic biomass upgrading, which converts abundant and renewable feedstocks into commercially desirable fuels and chemicals. Industrial applications require catalysts that maintain optimal reactivity over long time scales, yet at typical reaction temperatures, Lewis acidic Beta z...

  14. Mutations in LPIN1 Cause Recurrent Acute Myoglobinuria in Childhood

    OpenAIRE

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H.; Hindi, Tareq; De Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M.; Pines, Ophry; Elpeleg, Orly

    2009-01-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2–7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-spec...

  15. Mutations in LPIN1 Cause Recurrent Acute Myoglobinuria in Childhood

    OpenAIRE

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H.; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M.; Pines, Ophry; Elpeleg, Orly

    2008-01-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2–7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-spec...

  16. Environ: E00343 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00343 Boswellia gum substance Crude drug alpha-Boswellic acid, beta-Boswellic acid...11391], beta-Phellandrene [CPD:C09877 C11392] Boswellia carterii, Boswellia bhaw-dajiana, Boswellia neglecta [TAX:246345], Boswell...ia [TAX:80276] Burseraceae (frankincense family) Boswellia ...oil-bearing gum Alpha,beta-Boswellic acid in the component might exist as condensed type. Crude drugs [BR:br...08305] Dicot plants: rosids Burseraceae (frankincense family) E00343 Boswellia gum substance ...

  17. [A new eremophilane derivative from Senecio dianthus].

    Science.gov (United States)

    Han, He-Dong; Hu, Hai-Qing; Li, Yan; Wang, Xiao-Ling

    2013-10-01

    A new eremophilane derivative, 4,5,11-trimethyl-9( 10), 7 ( 11) -eremophiladien-8-keto-12-carboxylic acid-beta-D-glucopyranoside( which named dianthuside A) 1 and four known compounds, 5,7,4'-trihydroxy-flavonone-3-0-beta-D-glucoside (2), quercetin-3-0-beta-D-glucoside(3) ,hyperin(4) and rutin(5) have been isolated from the aerial part of Senecio dianthus. Their structures were elucidated by physicochemical properties and spectroscopic data analysis. Compounds 2, 4 and 5 were isolated from this plant for the first time.

  18. Neurotoxic flying foxes as dietary items for the Chamorro people, Marianas Islands.

    Science.gov (United States)

    Banack, Sandra Anne; Murch, Susan J; Cox, Paul Alan

    2006-06-15

    Fanihi -- flying foxes (Pteropus mariannus mariannus, Pteropodidae) -- are a highly salient component of the traditional Chamorro diet. A neurotoxic, non-protein amino acid, beta-methylamino-l-alanine (BMAA) accumulates in flying foxes, which forage on the seeds of Cycas micronesica (Cycadaceae) in Guam's forests. BMAA occurs throughout flying fox tissues both as a free amino acid and in a protein-bound form. It is not destroyed by cooking. Protein-bound BMAA also remains in cycad flour which has been washed and prepared by the Chamorro people as tortillas, dumplings, and thickened soups. Other animals that forage on cycad seeds may also provide BMAA inputs into the traditional Chamorro diet.

  19. Genetic heterogeneity in Gaucher disease: physicokinetic and immunologic studies of the residual enzyme in cultured fibroblasts from non-neuronopathic and neuronopathic patients.

    Science.gov (United States)

    Grabowski, G A; Goldblatt, J; Dinur, T; Kruse, J; Svennerholm, L; Gatt, S; Desnick, R J

    1985-07-01

    To elucidate the genetic heterogeneity in the three major phenotypic subtypes of Gaucher disease, the residual acid beta-glucosidase in fibroblasts from patients with all three subtypes from different ethnic and demographic groups was investigated by comparative kinetic, thermostability, and immunotitration studies. The kinetic studies delineated three distinct groups (designated A, B, and C) of residual activities with characteristic responses to the enzyme modifiers, taurocholate (or phosphatidylserine), and glucosyl sphingosine (or N-hexyl glucosyl sphingosine); Group A residual enzymes responded normally to these modifiers. All neuronopathic patients (types 2 and 3) and most non-Jewish, non-neuronopathic patients (type 1) had group A residual activities and thus could not be distinguished by their kinetic properties. Group B residual enzymes had markedly abnormal responses to these modifiers. All Ashkenazi and only two non-Jewish type 1 patients had group B residual activities. Group C residual activity had an intermediate response to all modifiers and represented a single Afrikaner type 1 patient. Pedigree studies indicated that this patient was a genetic compound for the group A (type 2) and group B (type 1) mutations. Thermostability studies showed additional heterogeneity of the residual activities within the three kinetic groups. Group A (type 2) and group B (type 1) enzymes had similarly decreased thermostabilities. In contrast, group A (type 1) residual activities were heterogeneous; three classes of thermostabilities were found among these enzymes: normal, decreased, and increased. Immunotitration of equal amounts of the normal or Gaucher disease beta-glucosidase activities with monospecific IgG indicated that the enzyme proteins from most Gaucher disease patients were antigenically altered and/or that large amounts of catalytically abnormal or inactive antigen were present. A decreased amount of antigenically and catalytically normal enzyme was present

  20. A theoretical study on C-COOH homolytic bond dissociation enthalpies.

    Science.gov (United States)

    Shi, Jing; Huang, Xiong-Yi; Wang, Jun-Peng; Li, Run

    2010-06-01

    The knowledge of C-COOH homolytic bond dissociation enthalpies (BDEs) is of great importance in understanding various chemical and biochemical processes involving the decarboxylation reaction. In the present study, the density functional theory (DFT method), B3P86/6-311++G(2df,2p)//B3LYP/6-31+G(d), is found to be reliable to predict the C-COOH BDE of various structurally unrelated carboxylic acids. The mean absolute deviation (MAD) and root-mean-square deviation (rmsd) of this optimal method are equal to 2.0 and 2.5 kcal/mol, respectively. With the authorized theoretical protocol in hand, an extensive C-COOH BDE scale containing over 100 carboxylic acids has been established. The availability of this body of data enabled a detailed investigation of remote substituent effect on four types of carboxylic acids, including para-substituted benzoic acid, beta-substituted cis-propenoic acid, beta-substituted trans-propenoic acid, and substituted propiolic acid. Also with the C-COOH BDE data obtained in this work, an excellent linear relationship has been found between the C-COOH BDE of carboxylic acids and the C-H BDE of their hydrocarbon analogues. After comparing the energy barrier of the Pd-catalyzed decarboxylation reaction (DeltaG(decarboxylation)++) with the related C-COOH BDE, a negative correlation between the DeltaG(decarboxylation)++ and the C-COOH BDE was found.

  1. Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase.

    Science.gov (United States)

    Clark-Taylor, Tonya; Clark-Taylor, Benjamin E

    2004-01-01

    Long chain acyl-CoA dehydrogenase (LCAD) has recently been shown to be the mitochondrial enzyme responsible for the beta-oxidation of branched chain and unsaturated fatty acids [Biochim. Biophys. Acta 1393 (1998) 35; Biochim. Biophys. Acta 1485 (2000) 121]. Whilst disorders of short, medium and very long chain acyl dehydrogenases are known, there is no known disorder of LCAD deficiency in humans. Experimental LCAD deficiency in mice shows an acyl-carnitine profile with prominent elevations of unsaturated fatty acid metabolites C14:1 and C14:2 [Hum. Mol. Genet. 10 (2001) 2069]. A child with autism whose acyl-carnitine profile also shows these abnormalities is presented, and it is hypothesized that the child may have LCAD deficiency. Additional metabolic abnormalities seen in this patient include alterations of TCA energy production, ammonia detoxification, reduced synthesis of omega-3 DHA, and abnormal cholesterol metabolism. These metabolic changes are also seen as secondary abnormalities in dysfunction of fatty acid beta-oxidation, and have also been reported in autism. It is hypothesized that LCAD deficiency may be a cause of autism. Similarities between metabolic disturbances in autism, and those of disorders of fatty acid beta-oxidation are discussed.

  2. Bioactive phytochemicals and antioxidant activity in fresh and dried lychee fractions1

    Directory of Open Access Journals (Sweden)

    Estela de Rezende Queiroz

    Full Text Available Fruit of the lychee cv. Bengal are approximately 50% peel and seeds, which are discarded. These by-products have antioxidant compounds which are capable of blocking the harmful effects of free radicals in the body. Bioactive compounds (ascorbic acid, beta-carotene, lycopene and phenols and antioxidant activity were evaluated in different extracts, both fresh and dried at 45 °C, of the skin, pulp and seeds of the lychee, which were subjected to principal component analysis to clarify which of the compounds are responsible for this activity. Principal component analysis explained 82.90% of the variance of the antioxidant profile of the lychee. The peel displayed higher levels of phenols, ascorbic acid, beta-carotene and antioxidant activity, while the seeds stood out due to their levels of lycopene. With drying, there was a decrease in the levels of ascorbic acid and beta-carotene and in antioxidant activity, with an increase in the levels of phenols and lycopene. The antioxidant activity found in the peel and seeds of the lychee is high, and is mainly due to ascorbic acid and beta-carotene, as demonstrated by principal component analysis, allowing the use of these fractions as sources of natural antioxidants.

  3. A study of fluorescence properties of citrinin in {beta}-cyclodextrin aqueous solution and different solvents

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Youxiang [Institute of Quality Standard and Testing Technology for Agro-products, Hubei Academy of Agricultural Sciences, Wuhan, Hubei Province 430064 (China); Chen Jianbiao; Dong Lina; Lu Liang [College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province 430070 (China); Chen Fusheng [College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province 430070 (China); Key Laboratory of Food Safety Evaluation of the Ministry of Agriculture, Wuhan, Hubei Province 430070 (China); National Key Laboratory of Agro-microbiology, Wuhan, Hubei Province 430070 (China); Hu Dingjin [Institute of Quality Standard and Testing Technology for Agro-products, Hubei Academy of Agricultural Sciences, Wuhan, Hubei Province 430064 (China); Wang Xiaohong, E-mail: wxh@mail.hzau.edu.cn [College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province 430070 (China); Key Laboratory of Food Safety Evaluation of the Ministry of Agriculture, Wuhan, Hubei Province 430070 (China)

    2012-06-15

    Citrinin (CIT) is a nephrotoxic mycotoxin initially isolated from filamentous fungus Penicilliu citrinum. It was later isolated from several other species, such as Aspergillus and Monascus. It has a conjugated, planar structure that gives it a natural fluorescence ability, which can be used to develop sensitive methods for detecting CIT in food. In this paper, we used the spectrofluorescence technique to study the effects of pH value, {beta}-cyclodextrin ({beta}-CD) and organic solvents on the CIT fluorescence intensity. The results show that lower pH value, aceitc acid, {beta}-CD and acetonitrile can induce a higher fluorescence intensity of CIT, but methanol or H{sub 2}O has a decreasing effect on the fluorescence intensity of CIT. Findings in this study provide a theoretical basis for development of a high sensitivity fluorescence-based trace analysis for CIT detection. - Highlights: Black-Right-Pointing-Pointer The effects of pH, solvents and {beta}-CD on the fluorescence of citrinin are analyzed. Black-Right-Pointing-Pointer [H]{sup +}, acetic acid, {beta}-CD and acetonitrile can induce CIT fluorescence enhancement. Black-Right-Pointing-Pointer Methanol and H{sub 2}O can induce CIT fluorescence reduction. Black-Right-Pointing-Pointer The 1:1 inclusion complex of CIT/{beta}-CD can form in acidic phosphate solution.

  4. Heterocyclyl linked anilines and benzaldehydes as precursors for biologically significant new chemical entities

    Indian Academy of Sciences (India)

    Raman K Verma; Vijay Kumar; Prithwish Ghosh; Lalit K Wadhwa

    2012-09-01

    Benzylidene and benzyl thiazolidinediones, oxazolidinediones, isoxazolidinediones and their acyclic analogs like alpha alkylthio/alkoxy phenylpropanoic acids, beta-keto esters and tyrosine-based compounds possess broad therapeutic potential in general and as Peroxisome Proliferator Activated Receptors (PPARs) agonists in particular in the management of hyperglycemia and hyperlipidaemia for the treatment of Type 2 Diabetes (T2D). We have synthesised and characterized some novel and suitably substituted heterocyclyl linked benzaldehydes and anilines, which can be easily and very readily derivatized to all the above mentioned classes to generate new chemical entities of broader biological significance. Synthesis of their benzylidene thiazolidinedione and diethyl malonate and also benzyl diethyl malonate and alpha-bromoesters derivatives is reported in some of the cases in the present work.

  5. Supplements and sports.

    Science.gov (United States)

    Jenkinson, David M; Harbert, Allison J

    2008-11-01

    Use of performance-enhancing supplements occurs at all levels of sports, from professional athletes to junior high school students. Although some supplements do enhance athletic performance, many have no proven benefits and have serious adverse effects. Anabolic steroids and ephedrine have life-threatening adverse effects and are prohibited by the International Olympic Committee and the National Collegiate Athletic Association for use in competition. Blood transfusions, androstenedione, and dehydroepiandrosterone are also prohibited in competition. Caffeine, creatine, and sodium bicarbonate have been shown to enhance performance in certain contexts and have few adverse effects. No performance benefit has been shown with amino acids, beta-hydroxy-beta-methylbutyrate, chromium, human growth hormone, and iron. Carbohydrate-electrolyte beverages have no serious adverse effects and can aid performance when used for fluid replacement. Given the widespread use of performance-enhancing supplements, physicians should be prepared to counsel athletes of all ages about their effectiveness, safety, and legality.

  6. Preparative separation and identification of derivatized beta-methylphenylalanine enantiomers by chiral SFC, HPLC and NMR for development of new peptide ligand mimetics in drug discovery.

    Science.gov (United States)

    Nogle, Lisa M; Mann, Charles W; Watts, William L; Zhang, Yingru

    2006-03-03

    A direct preparative purification of all four isomers of the unnatural amino acid beta-methylphenylalanine was achieved using supercritical fluid chromatography (SFC) with stacked-injection. Final purification of the Cbz-methyl ester derived isomers was performed on a Daicel Chiralpak AD-H column (20 mm x 250 mm), using 50:50 methanol/ethanol as the organic modifier and resulted in purification of over 3.4 g of material in 6.25 h with >90% total recovery. The absolute stereochemical assignment of the purified amino acids was determined through a combination of chiral HPLC, NMR and optical rotation studies. To our knowledge, this is the first reported preparative approach that has yielded all four compounds in a single chromatographic run.

  7. Adult type 3 Gaucher disease as manifestation of R463C/Rec Nci I mutation: first reported case in the world literature.

    Science.gov (United States)

    Chauhan, V; Kumar, R V; Mahesh, D M; Kashyap, R; Thakur, S

    2013-05-01

    Gaucher disease is the most common lysosomal storage disorder. It is autosomal recessive in nature and results from mutations in the GBA gene coding for acid beta glucosidase. It is classified into three types based on CNS involvement and its severity. Type 3, or chronic neuronopathic Gaucher disease, generally has an onset in childhood and by definition, includes all patients with any form of neurologic involvement who have survived the first few years of life. Here we present a 36 year old male patient presenting with hip pain showing bilateral avascular necrosis of femoral head with massive splenomegaly and on evaluation, showed mental retardation, seizures, bilateral vertical and horizontal gaze palsies and eventually turned out to be type 3b Gaucher disease. This is the first case of Type 3 Gaucher disease being reported from India with mutation analysis and only case of Type 3 Gaucher disease in world literature showing R463C/Rec Nci I mutation.

  8. Two glucosylated abscisic acid derivates from avocado seeds (Persea americana Mill. Lauraceae cv. Hass).

    Science.gov (United States)

    del Refugio Ramos, María; Jerz, Gerold; Villanueva, Socorro; López-Dellamary, Fernando; Waibel, Reiner; Winterhalter, Peter

    2004-04-01

    Phytochemical investigation of avocado seed material (Persea americana Mill., Lauraceae) resulted in the isolation of two glucosylated abscisic acid derivates. One of these was not known as a natural product and can be regarded as a potential 'missing link' in abscisic acid metabolism in plants. After fractionation by high-speed countercurrent chromatography, and multiple steps of column chromatography, structures were elucidated by 1D-, 2D-NMR, electrospray-MS to be the novel beta-d-glucoside of (1'S,6'R)-8'-hydroxyabscisic acid, and (1'R,3'R,5'R,8'S)-epi-dihydrophaseic acid beta-d-glucoside. Absolute configuration was determined by circulardichroism, optical rotation, and by NOE experiments.

  9. Novel lipid constituents identified in seeds of Nigella sativa (Linn)

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, B.K.; Verma, Manjul; Gupta, Meenal [Vikram University (India). School of Studies in Chemistry and Biochemistry]. E-mail: bkmehta11@yahoo.com

    2008-07-01

    Novel lipids were isolated from the unsaponifiable matter extracted from seeds of Nigella sativa Linn by using n-hexane. The new dienoate and two monoesters were the new lipids identified by spectral (IR, {sup 1}H- and {sup 13}C-NMR spectra, mass spectrum, elemental analysis) and chemical analysis. The dienoate (1) was identified as methylnonadeca-15,17-dienoate and two monoesters were identified as pentyl hexadec-12-enoate (2) and pentyl pentadec-11-enoate (3). Linoleic acid, oleic acid, {beta}-sitosterol and stigmasterol were identified as part of the lipid structures. All compounds exhibited moderate activity against Staphylococcus aureus and poor activity against shigella spp, and Klebsiella pneumoniae. (author)

  10. Some aspects of the mitochondrial oxidative metabolism in human atrial tissue during cardiopulmonary by-pass.

    Science.gov (United States)

    Corbucci, G G; Gasparetto, A; Antonelli, M; Bufi, M; De Blasi, R A

    1987-01-01

    Following previous research on the hypoxic cell in human circulatory shock, the present work has investigated some mitochondrial oxidative aspects in atrial biopsies taken during cardiopulmonary by-pass. Cardioplegic solution and hypothermia were administered to 10 patients and the atrial samples were collected before and after aortic clamping. The results show a cellular protective effect of cardioplegia and hypothermia on the electron-transport chain, even if the enzymes with high KmO2 appear to be more sensitive to ischaemia. The results suggest a metabolic injury rather than an oxidative damage due to the induced ischaemia, alterations to fatty-acid beta-oxidation being especially notable. Because of the unchanged oxidative capacities, the oxyradical generation and the peroxidative damage appear to be irrelevant in the ischaemic period and during the course of reperfusion. Further studies are needed to elucidate the metabolic damage and the therapeutic implications due to the induced ischaemia in the myocardial cell during the aortic clamping.

  11. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

    Science.gov (United States)

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M; Pines, Ophry; Elpeleg, Orly

    2008-10-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy.

  12. Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Gene-Targeted Mice.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Medium-chain acyl-CoA dehydrogenase (MCAD deficiency is the most common inherited disorder of mitochondrial fatty acid beta-oxidation in humans. To better understand the pathogenesis of this disease, we developed a mouse model for MCAD deficiency (MCAD by gene targeting in embryonic stem (ES cells. The MCAD mice developed an organic aciduria and fatty liver, and showed profound cold intolerance at 4 degrees C with prior fasting. The sporadic cardiac lesions seen in MCAD mice have not been reported in human MCAD patients. There was significant neonatal mortality of MCAD pups demonstrating similarities to patterns of clinical episodes and mortality in MCAD-deficient patients. The MCAD-deficient mouse reproduced important aspects of human MCAD deficiency and is a valuable model for further analysis of the roles of fatty acid oxidation and pathogenesis of human diseases involving fatty acid oxidation.

  13. Acetogenesis does not replace ketogenesis in fasting piglets infused with hexanoate.

    Science.gov (United States)

    Adams, S H; Odle, J

    1998-06-01

    The current studies were performed to better understand the physiological relevance of acetate in the poorly ketogenic piglet and to determine if endogenous acetogenesis rises with increased mitochondrial fatty acid beta-oxidation, analogous to ketogenesis. Plasma acetate concentration values in newborn, fasted, or suckled piglets (230-343 microM) were at least 10-fold higher than the ketone bodies, a pattern opposite to that in 24- to 48-h suckled rats (77-175 microM). Employing continuous infusion techniques with sodium [3H]acetate tracer in fasting approximately 40-h-old piglets, acetate rate of appearance (Ra) was found to be 34 +/- 4 micromol . min-1 . kg body wt-1. This basal Ra was double that observed in animals coinfused with sodium [1-14C]hexanoate (P ketogenesis in vivo.

  14. Antimutagenic activity of some naturally occurring compounds towards cigarette-smoke condensate and benzo(a)pyrene in the Salmonella/microsome assay

    Energy Technology Data Exchange (ETDEWEB)

    Terwel, L.; van der Hoeven, J.C.

    1985-10-01

    Several compounds, occurring in food, were tested for antimutagenic activity towards cigarette-smoke condensate (CSC) and benzo(a)pyrene (BaP). Antimutagenicity was determined in the Salmonella/microsome test, with tester strain TA98, in the presence of rat-liver homogenate. Dose-response curves did show reduction of CSC- and BaP-induced mutagenicity by ellagic acid, riboflavin and chlorophyllin. Chlorophyll a and chlorophyll b, although less distinct, also inhibited CSC- and BaP-induced mutagenicity. Ascorbic acid, beta-carotene, tocopherol acetate, chlorogenic acid and butyl hydroxyanisole did not have any influence on the mutagenicity of CSC and BaP. The similarity in results for cigarette-smoke condensate and for BaP indicates that a general mechanism may be involved in the inhibition of CSC- and BaP-induced mutagenicity.

  15. [Beta-3 adrenergic receptor--structure and role in obesity and metabolic disorders].

    Science.gov (United States)

    Wiejak, J; Wyroba, E

    1999-01-01

    Structure and essential motifs of beta 3-adrenergic receptor (known previously as atypical beta-AR), which plays a central role in regulation of lipid metabolism have been described. Obesity results from an imbalance between caloric intake and energy expenditure. The consequence of catecholamine activation of beta 3-AR is increased mobilization of fatty acids from triglyceride stores (lipolysis) in brown and white adipose tissue as well as increased fatty acid beta-oxidation and heat-production via UCP-1 (thermogenesis) in brown adipose tissue. A pharmacokinetic effects of beta 3-agonists and putative involvement of Trp/Arg mutation in beta 3-AR gene in obesity and another metabolic disorders have been discussed.

  16. Practical synthesis of enantiomerically pure beta2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes.

    Science.gov (United States)

    Chi, Yonggui; English, Emily P; Pomerantz, William C; Horne, W Seth; Joyce, Leo A; Alexander, Lane R; Fleming, William S; Hopkins, Elizabeth A; Gellman, Samuel H

    2007-05-01

    Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral iminium ion, generated from a readily prepared precursor, provides alpha-substituted-beta-amino aldehydes with 85:15 to 90:10 dr. The alpha-substituted-beta-amino aldehydes can be reduced to beta-substituted-gamma-amino alcohols, the major diastereomer of which can be isolated via crystallization or column chromatography. The amino alcohols are efficiently transformed to protected beta2-amino acids, which are valuable building blocks for beta-peptides, natural products, and other interesting molecules. Because conditions for the aminomethylation and subsequent reactions are mild, beta2-amino acid derivatives with protected functional groups in the side chain, such as beta2-homoglutamic acid, beta2-homotyrosine, and beta2-homolysine, can be prepared in this way. The synthetic route is short, and purifications are simple; therefore, this method enables the preparation of protected beta2-amino acids in useful quantities.

  17. Oxygen radicals shaping evolution: why fatty acid catabolism leads to peroxisomes while neurons do without it: FADH₂/NADH flux ratios determining mitochondrial radical formation were crucial for the eukaryotic invention of peroxisomes and catabolic tissue differentiation.

    Science.gov (United States)

    Speijer, Dave

    2011-02-01

    Oxygen radical formation in mitochondria is a highly important, but incompletely understood, attribute of eukaryotic cells. I propose a kinetic model in which the ratio between electrons entering the respiratory chain via FADH₂ or NADH is a major determinant in radical formation. During the breakdown of glucose, this ratio is low; during fatty acid breakdown, this ratio is much higher. The longer the fatty acid, the higher the ratio and the higher the level of radical formation. This means that very long chain fatty acids should be broken down without generation of FADH₂ for mitochondria. This is accomplished in peroxisomes, thus explaining their role and evolution. The model explains many recent observations regarding radical formation by the respiratory chain. It also sheds light on the reasons for the lack of neuronal fatty acid (beta-) oxidation and for beneficial aspects of unsaturated fatty acids. Last but not least, it has very important implications for all models describing eukaryotic origins.

  18. Triterpene saponins from Chenopodium quinoa Willd.

    Science.gov (United States)

    Kuljanabhagavad, Tiwatt; Thongphasuk, Piyanut; Chamulitrat, Walee; Wink, Michael

    2008-06-01

    Twenty triterpene saponins (1-20) have been isolated from different parts of Chenopodium quinoa (flowers, fruits, seed coats, and seeds) and their structures have been elucidated by analysis of chemical and spectroscopic data including 1D- and 2D-NMR. Four compounds (1-4) were identified: 3beta-[(O-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl)oxy]-23-oxo-olean-12-en-28-oic acid beta-d-glucopyranoside (1), 3beta-[(O-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl)oxy]-27-oxo-olean-12-en-28-oic acid beta-d-glucopyranoside (2), 3-O-alpha-l-arabinopyranosyl serjanic acid 28-O-beta-d-glucopyranosyl ester (3), and 3-O-beta-d-glucuronopyranosyl serjanic acid 28-O-beta-d-glucopyranosyl ester (4). The following known compounds have not previously been reported as saponin constituents from the flowers and the fruits of this plant: two bidesmosides of serjanic acid (5,6), four bidesmosides of oleanolic acid (7-10), five bidesmosides of phytolaccagenic acid (11-15), four bidesmosides of hederagenin (16-19), and one bidesmoside of 3beta,23,30-trihydroxy olean-12-en-28-oic acid (20). The cytotoxicity of these saponins and their aglycones was tested in HeLa cells. Induction of apoptosis in Caco-2 cells by bidesmosidic saponins 1-4 and their aglycones I-III was determined by flow cytometric DNA analysis. The saponins with an aldehyde group were most active. The relationships between structure and cytotoxic activity of saponins and their aglycones are discussed.

  19. Gaucher disease: Pseudoreversion of a disease mutation`s effects--implications for structure/function and genotype/phenotype correlations

    Energy Technology Data Exchange (ETDEWEB)

    Ponce, E.; Mear, J; Grabowski, G.A. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)

    1994-09-01

    Numerous mutations ({approximately}45) of the acid {beta}-glucosidase gene have been identified in patients with Gaucher disease. Many of these have been characterized by partial sequencing of cDNAs derived by RT-PCR or PCR of genomic DNA. In addition, genotype/phenotype correlations have been based on screening for known mutations. Thus, only a part of the gene is characterized in any population of affected patients. Several Gaucher disease alleles contain multiple, authentic point mutations that raises concern about conclusions based on only partial genetic characterization. Several wild-type cDNAs for acid {beta}-glucosidase have been sequenced. One contained a cloning artifact encoding R495H. We expressed this cDNA and showed that the R495H enzyme had normal kinetic and stability properties. A disease-associated allele encoding R496H has been found by several groups. The close association and similarities of these two substitutions led us to question the disease casuality of the R496H allele. To evaluate this, we created and/or expressed cDNAs encoding R495, R496 (wild-type), (R495H, R496), (R495, R496H) and (R495H, R496H). The (wild-type) and (R495H, R496) enzymes had indistinguishable properties whereas the (R495, R496H) enzyme was essentially inactive. The introduction of both mutations (R495H, R496H) produced an enzyme whose activity was 25 to 50% of the wild-type. These results indicate that a pseudoreversion to a functional enzyme can occur by introducing a functionally neutral mutation together with a severe mutation. These results have major implications to structure/function and genotype/phenotype correlations in this disease.

  20. Quantitative 'Omics Analyses of Medium Chain Length Polyhydroxyalkanaote Metabolism in Pseudomonas putida LS46 Cultured with Waste Glycerol and Waste Fatty Acids.

    Directory of Open Access Journals (Sweden)

    Jilagamazhi Fu

    Full Text Available Transcriptomes and proteomes of Pseudomonas putida LS46 cultured with biodiesel-derived waste glycerol or waste free fatty acids, as sole carbon sources, were compared under conditions that were either permissive or non-permissive for synthesis of medium chain length polyhydroxyalkanoates (mcl-PHA. The objectives of this study were to elucidate mechanisms that influence activation of biopolymer synthesis, intra-cellular accumulation, and monomer composition, and determine if these were physiologically specific to the carbon sources used for growth of P. putida LS46. Active mcl-PHA synthesis by P. putida LS46 was associated with high expression levels of key mcl-PHA biosynthesis genes and/or gene products including monomer-supplying proteins, PHA synthases, and granule-associated proteins. 'Omics data suggested that expression of these genes were regulated by different genetic mechanisms in P. putida LS46 cells in different physiological states, when cultured on the two waste carbon sources. Optimal polymer production by P. putida LS46 was primarily limited by less efficient glycerol metabolism during mcl-PHA synthesis on waste glycerol. Mapping the 'Omics data to the mcl-PHA biosynthetic pathway revealed significant variations in gene expression, primarily involved in: 1 glycerol transportation; 2 enzymatic reactions that recycle reducing equivalents and produce key mcl-PHA biosynthesis pathway intermediates (e.g. NADH/NADPH, acetyl-CoA. Active synthesis of mcl-PHAs was observed during exponential phase in cultures with waste free fatty acids, and was associated with the fatty acid beta-oxidation pathway. A putative Thioesterase in the beta-oxidation pathway that may regulate the level of fatty acid beta-oxidation intermediates, and thus carbon flux to mcl-PHA biosynthesis, was highly up-regulated. Finally, the data suggested that differences in expression of selected fatty acid metabolism and mcl-PHA monomer-supplying enzymes may play a role in

  1. Correlation between the different chain lengths of free fatty acid oxidation and ability of trophoblastic invasion

    Institute of Scientific and Technical Information of China (English)

    Yu Huan; Yang Zi; Ding Xiaoyan; Wang Yanling; Han Yiwei

    2014-01-01

    Background Preeclampsia (PE) is associated with abnormal fatty acid beta-oxidation (FAO),especially metabolic disorders of long-chain fatty acid oxidation.The role of FAO dysfunction in inadequate invasion is unclear.The aim of this study was to explore the influence of various lengths fatty acids oxidation on invasiveness of trophoblasts.Methods Primary human trophoblast cells and HTR8/SVneo cells were treated with fatty acids of various lengths.Morphological changes,lipid deposition and ultrastructure changes of trophoblast cells were detected.Cells invasiveness was determined by transwell insert.CPT1,CPT2 and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) protein expression were analyzed.The correlation between intracellular lipid droplets deposition and cells invasiveness was evaluated.Results Cells treated with long-chain fatty acids showed significant increased lipid droplets deposition,severe mitochondrial damage,decreased CPT2 and LCHAD protein expression (P <0.05) but no significant difference in CPT1 protein expression (P >0.05).Invasiveness of the trophoblast cells of the LC-FFA group significantly decreased (P <0.05).Intracellular lipid droplets deposition was negatively correlated with invasivenss (R=-0.745,P <0.05).Conclusion Trophoblast cells after stimulation with long chain fatty acids exist fatty acid oxidation disorders,and reduce the ability of trophoblastic invasion.

  2. Novel Directions for Diabetes Mellitus Drug Discovery

    Science.gov (United States)

    Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Wang, Shaohui

    2012-01-01

    Introduction Diabetes mellitus impacts almost 200 million individuals worldwide and leads to debilitating complications. New avenues of drug discovery must target the underlying cellular processes of oxidative stress, apoptosis, autophagy, and inflammation that can mediate multi-system pathology during diabetes mellitus. Areas Covered We examine novel directions for drug discovery that involve the β-nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide, the cytokine erythropoietin, the NAD+-dependent protein histone deacetylase SIRT1, the serine/threonine-protein kinase mammalian target of rapamycin (mTOR), and the wingless pathway. Implications for the targeting of these pathways that oversee gluconeogenic genes, insulin signaling and resistance, fatty acid beta-oxidation, inflammation, and cellular survival are presented. Expert Opinion Nicotinamide, erythropoietin, and the downstram pathways of SIRT1, mTOR, forkhead transcription factors, and wingless signaling offer exciting prospects for novel directions of drug discovery for the treatment of metabolic disorders. Future investigations must dissect the complex relationship and fine modulation of these pathways for the successful translation of robust reparative and regenerative strategies against diabetes mellitus and the complications of this disorder. PMID:23092114

  3. Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.

    Directory of Open Access Journals (Sweden)

    Ghulam Hussain

    Full Text Available The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS. Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

  4. Welfare assessment based on metabolic and endocrine aspects in primiparous cows milked in a parlor or with an automatic milking system.

    Science.gov (United States)

    Abeni, F; Calamari, L; Calza, F; Speroni, M; Bertoni, G; Pirlo, G

    2005-10-01

    An automatic milking system (AMS) was compared with a traditional milking parlor (MP) to evaluate metabolic and psycho-physiological aspects of animal welfare. Twenty Italian Friesian heifers were allocated to 2 groups of 10 cows each after calving and maintained in the same free-stall barn. The first group was milked twice daily in a MP; the second group was milked in a single box AMS. Feed and diet characteristics were analyzed. Health status and body condition score (BCS) were evaluated in each cow. Blood samples were obtained from -14 to 154 d in milk (DIM) to determine metabolic profile and basal concentrations of cortisol in plasma. Data collected from 10 cows per group were processed. No significant difference was detected in milk yield, BCS, and energy-related metabolites (glucose, nonesterified fatty acids, beta-hydroxybutyrate, and triglycerides) from cows in MP or in AMS during the first 22 wk of lactation. These results, jointly with the absence of significant differences in plasma metabolites related to protein metabolism, mineral metabolism, and liver function during the first 22 wk of lactation, indicates that cows in AMS did not suffer metabolically. Greater basal concentrations of plasma cortisol in AMS cows, even if absolute values were considered to be in an acceptable range, might indicate chronic stress in these primiparous cows. Further research is necessary to confirm this hypothesis.

  5. Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters.

    Science.gov (United States)

    Jang, Eun-Mi; Choi, Myung-Sook; Jung, Un Ju; Kim, Myung-Joo; Kim, Hye-Jin; Jeon, Seon-Min; Shin, Su-Kyung; Seong, Chi-Nam; Lee, Mi-Kyung

    2008-11-01

    This study investigated the effect of curcumin (0.05-g/100-g diet) supplementation on a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) fed to hamsters, one of the rodent species that are most closely related to humans in lipid metabolism. Curcumin significantly lowered the levels of free fatty acid, total cholesterol, triglyceride, and leptin and the homeostasis model assessment of insulin resistance index, whereas it elevated the levels of high-density lipoprotein cholesterol and apolipoprotein (apo) A-I and paraoxonase activity in plasma, compared with the control group. The levels of hepatic cholesterol and triglyceride were also lower in the curcumin group than in the control group. In the liver, fatty acid beta-oxidation activity was significantly higher in the curcumin group than in the control group, whereas fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and acyl coenzyme A:cholesterol acyltransferase activities were significantly lower. Curcumin significantly lowered the lipid peroxide levels in the erythrocyte and liver compared with the control group. These results indicate that curcumin exhibits an obvious hypolipidemic effect by increasing plasma paraoxonase activity, ratios of high-density lipoprotein cholesterol to total cholesterol and of apo A-I to apo B, and hepatic fatty acid oxidation activity with simultaneous inhibition of hepatic fatty acid and cholesterol biosynthesis in high-fat-fed hamsters.

  6. Metaproteomics provides functional insight into activated sludge wastewater treatment.

    Directory of Open Access Journals (Sweden)

    Paul Wilmes

    Full Text Available BACKGROUND: Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR. METHODOLOGY/PRINCIPAL FINDINGS: A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism "Candidatus Accumulibacter phosphatis". When EBPR failed, the sludge was dominated by tetrad-forming alpha-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from "Candidatus Accumulibacter phosphatis" and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid beta oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. CONCLUSIONS/SIGNIFICANCE: Importantly, this study provides direct evidence linking the metabolic activities of "Accumulibacter" to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models.

  7. Physico-chemical and Antioxidant Properties of Different Pumpkin Cultivars Grown in China

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    2015-08-01

    Full Text Available To obtain more detailed knowledge of the differences among major pumpkin species grown in China, physico-chemical and antioxidant properties of four pumpkin cultivars (Miben, Hongli, Lvli, Xihulu were characterized and compared. Dry matter, total soluble solids, titratable acidity, fruit color, protein, fat, sugars, minerals, amino acids, &beta -carotene, L-ascorbic acid, total phenols and antioxidant activities (DPPH and FRAP were measured in the studied cultivars. The results showed great differences in the composition and characteristics of the pumpkin cultivars. Miben exhibited the highest concentration of dry matter, fat, Total Soluble Solid (TSS, Titratable Acidity (TA, sucrose, &beta-carotene, K, P, Fe, Zn and aspartic acid. Hongli had the highest concentration protein, L-ascorbic acid, Na, Ca, Mg and all individual amino acids except for asparitic acid. Lvli exhibited significantly (p<0.05 higher antioxidant activities (DPPH and FRAP, which are highly related to total phenols content in pumpkin fruits (r = 0.94 and r = 0.98, respectively. Principal Component Analysis (PCA allowed the four pumpkin cultivars to be differentiated clearly based on all these physico-chemical and antioxidant properties determined in the study.

  8. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease.

    Science.gov (United States)

    Chen, Qiang; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

    2011-06-17

    Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor α (PPARα), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  9. Supercritical Fluid Extraction of Plutonium and Americium from Soil

    Energy Technology Data Exchange (ETDEWEB)

    Fox, R.V.; Mincher, B.J.

    2002-05-23

    Supercritical fluid extraction (SFE) of plutonium and americium from soil was successfully demonstrated using supercritical fluid carbon dioxide solvent augmented with organophosphorus and beta-diketone complexants. Spiked Idaho soils were chemically and radiologically characterized, then extracted with supercritical fluid carbon dioxide at 2,900 psi and 65 C containing varying concentrations of tributyl phosphate (TBP) and thenoyltrifluoroacetone (TTA). A single 45 minute SFE with 2.7 mol% TBP and 3.2 mol% TTA provided as much as 88% {+-} 6.0 extraction of americium and 69% {+-} 5.0 extraction of plutonium. Use of 5.3 mol% TBP with 6.8 mol% of the more acidic beta-diketone hexafluoroacetylacetone (HFA) provided 95% {+-} 3.0 extraction of americium and 83% {+-} 5.0 extraction of plutonium in a single 45 minute SFE at 3,750 psi and 95 C. Sequential chemical extraction techniques were used to chemically characterize soil partitioning of plutonium and americium in pre-SFE soil samples. Sequential chemical extraction techniques demonstrated that spiked plutonium resides primarily (76.6%) in the sesquioxide fraction with minor amounts being absorbed by the oxidizable fraction (10.6%) and residual fractions (12.8%). Post-SFE soils subjected to sequential chemical extraction characterization demonstrated that 97% of the oxidizable, 78% of the sesquioxide and 80% of the residual plutonium could be removed using SFE. These preliminary results show that SFE may be an effective solvent extraction technique for removal of actinide contaminants from soil.

  10. Anti-inflammatory and analgesic components from "hierba santa," a traditional medicine in Peru.

    Science.gov (United States)

    Kawano, Marii; Otsuka, Mayumi; Umeyama, Kazuhiro; Yamazaki, Mikio; Shiota, Tetsuo; Satake, Motoyoshi; Okuyama, Emi

    2009-04-01

    "Hierba santa," a Peruvian herbal medicine, is used to alleviate many symptoms, including headache, hemorrhoids, fever, and rheumatism. Several Cestrum species are said to be the origin of hierba santa. Three lots of hierba santa: Cestrum auriculatum (herb 1 and herb 2) and C. hediundinum (herb 3), which were purchased from Peruvian markets at Cuzco (Andes area) and Equitos (Amazon area), respectively, were examined for their pharmacological activities and active components. Herbs 1-3 showed anti-inflammatory and analgesic activities in the in vivo writhing inhibition test in mouse and inhibited prostaglandin E(1)-, E(2)-, or ACh-induced contractions of guinea pig ileum in the Magnus method. Activity-based separation of each extract yielded cestrumines A and B, cestrusides A and B, a mixture of (+)- and (-)-pinoresinol glucosides, nicotiflorin, rutin, sinapoyl glucose, ursolic acid, beta-sitosteryl glucoside, and 2-sec-butyl-4,6-dihydroxyphenyl-beta-D: -glucopyranoside. Among them, cestrumine A and cestrusides A and B are new compounds. All three lots of hierba santa do not contain exactly the same active components.

  11. Characterization of five typical agave plants used to produce mezcal through their simple lipid composition analysis by gas chromatography.

    Science.gov (United States)

    Martínez-Aguilar, Juan Fco; Peña-Alvarez, Araceli

    2009-03-11

    Five agave plants typically used in Mexico for making mezcal in places included in the Denomination of Origin (Mexican federal law that establishes the territory within which mezcal can be produced) of this spirit were analyzed: Agave salmiana ssp. crassispina, A. salmiana var. salmiana, Agave angustifolia, Agave cupreata, and Agave karwinskii. Fatty acid and total simple lipid profiles of the mature heads of each plant were determined by means of a modified Bligh-Dyer extraction and gas chromatography. Sixteen fatty acids were identified, from capric to lignoceric, ranging from 0.40 to 459 microg/g of agave. Identified lipids include free fatty acids, beta-sitosterol, and groups of mono-, di-, and triacylglycerols, their total concentration ranging from 459 to 992 microg/g of agave. Multivariate analyses performed on the fatty acid profiles showed a close similarity between A. cupreata and A. angustifolia. This fact can be ascribed to the taxa themselves or differences in growing conditions, an issue that is still to be explored. These results help to characterize the agaves chemically and can serve to relate the composition of mezcals from various states of Mexico with the corresponding raw material.

  12. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

    Science.gov (United States)

    Andresen, B S; Olpin, S; Poorthuis, B J; Scholte, H R; Vianey-Saban, C; Wanders, R; Ijlst, L; Morris, A; Pourfarzam, M; Bartlett, K; Baumgartner, E R; deKlerk, J B; Schroeder, L D; Corydon, T J; Lund, H; Winter, V; Bross, P; Bolund, L; Gregersen, N

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting. To examine whether these different phenotypes are due to differences in the VLCAD genotype, we investigated 58 different mutations in 55 unrelated patients representing all known clinical phenotypes and correlated the mutation type with the clinical phenotype. Our results show a clear relationship between the nature of the mutation and the severity of disease. Patients with the severe childhood phenotype have mutations that result in no residual enzyme activity, whereas patients with the milder childhood and adult phenotypes have mutations that may result in residual enzyme activity. This clear genotype-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established. PMID:9973285

  13. Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu Qiuwei, E-mail: qiuwei_xu@merck.com; Vu, Heather; Liu Liping; Wang, Ting-Chuan; Schaefer, William H. [Merck Research Laboratories (United States)

    2011-04-15

    Mitochondrial toxicity has been a serious concern, not only in preclinical drug development but also in clinical trials. In mitochondria, there are several distinct metabolic processes including fatty acid {beta}-oxidation, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS), and each process contains discrete but often intimately linked steps. Interruption in any one of those steps can cause mitochondrial dysfunction. Detection of inhibition to OXPHOS can be complicated in vivo because intermediate endogenous metabolites can be recycled in situ or circulated systemically for metabolism in other organs or tissues. Commonly used assays for evaluating mitochondrial function are often applied to ex vivo or in vitro samples; they include various enzymatic or protein assays, as well as functional assays such as measurement of oxygen consumption rate, membrane potential, or acidification rates. Metabolomics provides quantitative profiles of overall metabolic changes that can aid in the unraveling of explicit biochemical details of mitochondrial inhibition while providing a holistic view and heuristic understanding of cellular bioenergetics. In this paper, we showed the application of quantitative NMR metabolomics to in vitro myotube cells treated with mitochondrial toxicants, rotenone and antimycin A. The close coupling of the TCA cycle to the electron transfer chain (ETC) in OXPHOS enables specific diagnoses of inhibition to ETC complexes by discrete biochemical changes in the TCA cycle.

  14. Anticancer Properties of PPARalpha-Effects on Cellular Metabolism and Inflammation.

    Science.gov (United States)

    Grabacka, Maja; Reiss, Krzysztof

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) have lately attracted much attention as therapeutic targets. Previously, PPAR ligands were associated with the treatment of diabetes, hyperlipidemia and cardiovascular diseases, as they modulate the expression of genes regulating glucose and lipid metabolism. Recently, PPAR ligands have been also considered as potential anticancer agents, with relatively low systemic toxicity. The emerging evidence for antiproliferative, proapoptotic, antiinflammatory and potential antimetastatic properties of PPARalpha ligands prompted us to discuss possible roles of PPARalpha in tumor suppression. PPARalpha activation can target cancer cells energy balance by blocking fatty acid synthesis and by promoting fatty acid beta-oxidation. In the state of limited nutrient availability, frequently presents in the tumor microenvironment, PPARalpha cooperates with AMP-dependent protein kinase in: (i) repressing oncogenic Akt activity, (ii) inhibiting cell proliferation, and (iii) forcing glycolysis-dependent cancer cells into "metabolic catastrophe." Other potential anticancer effects of PPARalpha include suppression of inflammation, and upregulation of uncoupling proteins (UCPs), which attenuates mitochondrial reactive oxygen species production and cell proliferation. In conclusion, there are strong premises that the low-toxic and well-tolerated PPAR ligands should be considered as new therapeutic agents to fight disseminating cancer, which represents the major challenge for modern medicine and basic research.

  15. Profile of eliglustat tartrate in the management of Gaucher disease

    Directory of Open Access Journals (Sweden)

    Sechi A

    2016-01-01

    Full Text Available Annalisa Sechi, Andrea Dardis, Bruno Bembi Regional Coordinator Center for Rare Diseases, Academic Hospital of Udine, Udine, Italy Abstract: Gaucher disease (GD is a lysosomal storage disorder caused by the deficient activity of acid beta glucosidase, with consequent accumulation of glucosylceramide in the spleen, liver, bone marrow, and various organs and tissues. Currently, the gold standard for GD treatment is enzyme replacement therapy (ERT. The efficacy of ERT in improving or stabilizing the visceral and hematological symptoms of GD is well-proven. However, since ERT has to be administered by frequent intravenous infusions, this therapeutic approach has an important impact on the patient’s quality of life. Eliglustat tartrate is a new substrate reduction therapy for GD, which acts as a specific and potent inhibitor of glucosylceramide synthase and can be administered orally. This review summarizes the results of the preclinical and clinical trials, which experimented with eliglustat, and discusses its possible role in the management of GD, when compared to the currently available treatments and the new experimental approaches. Keywords: Gaucher disease, enzyme replacement therapy, substrate reduction therapy, eliglustat tartrate

  16. Identification of a feedback loop involving beta-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease.

    Science.gov (United States)

    Schonauer, Sophie; Körschen, Heinz G; Penno, Anke; Rennhack, Andreas; Breiden, Bernadette; Sandhoff, Konrad; Gutbrod, Katharina; Dörmann, Peter; Raju, Diana N; Haberkant, Per; Gerl, Mathias J; Brügger, Britta; Zigdon, Hila; Vardi, Ayelet; Futerman, Anthony H; Thiele, Christoph; Wachten, Dagmar

    2017-03-03

    The lysosomal acid beta-glucosidase GBA1 and the non-lysosomal beta-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease. Using an experimental approach combining cell biology, biochemistry, and mass spectrometry, we show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. We propose a negative feed-back loop, in which sphingosine inhibits GBA2 activity in Gaucher cells, preventing further sphingosine accumulation and, thereby, cytotoxicity. Our findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of beta-glucosidase activity in general.

  17. Interaction of metal ions and amino acids - Possible mechanisms for the adsorption of amino acids on homoionic smectite clays

    Science.gov (United States)

    Gupta, A.; Loew, G. H.; Lawless, J.

    1983-01-01

    A semiempirical molecular orbital method is used to characterize the binding of amino acids to hexahydrated Cu(2+) and Ni(2+), a process presumed to occur when they are adsorbed in the interlamellar space of homoionic smectite clays. Five alpha-amino acids, beta-alanine, and gamma-aminobutyric acid were used to investigate the metal ion and amino acid specificity in binding. It was assumed that the alpha, beta, and gamma-amino acids would bind as bidentate anionic ligands, forming either 1:1 or 1:2 six-coordinated five, six, and seven-membered-ring chelate complexes, respectively. Energies of complex formation, optimized geometries, and electron and spin distribution were determined; and steric constraints of binding of the amino acids to the ion-exchanged cations in the interlamellar spacing of a clay were examined. Results indicate that hexahydrated Cu(2+) forms more stable complexes than hexahydrated Ni(2+) with all the amino acids studied. However, among these amino acids, complex formation does not favor the adsorption of the biological subset. Calculated energetics of complex formation and steric constraints are shown to predict that 1:1 rather than 1:2 metal-amino acid complexes are generally favored in the clay.

  18. Vegetables, fruit, and cancer prevention: a review.

    Science.gov (United States)

    Steinmetz, K A; Potter, J D

    1996-10-01

    In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented.

  19. Supplemental dietary protein for grazing dairy cows: reproduction, condition loss, plasma metabolites, and insulin.

    Science.gov (United States)

    Chapa, A M; McCormick, M E; Fernandez, J M; French, D D; Ward, J D; Beatty, J F

    2001-04-01

    An experiment was conducted over a 2-yr period to investigate the influence of grain crude protein (CP) and rumen undegradable protein (RUP) concentration on reproduction and energy status of dairy cows grazing annual ryegrass (Lolium multiflorum) and oats (Avena sativa). Holstein cows (n = 122) were blocked by calving group [partum (0 d postpartum) vs. postpartum (41 +/- 19 d postpartum at study initiation)] and assigned to grain supplements containing high CP [22.8% of dry matter (DM)], moderate CP (16.6%), or moderate CP (16.2%)] supplemented with RUP from blood meal and corn gluten meal. Postpartum condition loss was greater and first-service pregnancy rate was lower for partum-group cows receiving high CP grain supplements compared with control cows receiving moderate CP supplements. The RUP supplements reduced grain consumption, increased days to first estrus, and reduced first-service pregnancy rate of partum-group cows. The reproduction of postpartum group cows was unaffected by protein supplements. Plasma urea nitrogen was higher for cows fed high CP diets, but plasma ammonia nitrogen, glycated hemoglobin, nonesterified fatty acids, beta-hydoxybutyrate, glucose, and insulin concentrations were similar to cows fed moderate CP. Excess postpartum condition loss, coupled with inconsistent protein supplement effects on days to first service and first-service pregnancy rate, suggest that energy deprivation may have contributed to the low fertility experienced by grazing cows in this study.

  20. Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans.

    Directory of Open Access Journals (Sweden)

    Marc R Van Gilst

    2005-02-01

    Full Text Available Mammalian nuclear hormone receptors (NHRs, such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs, precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with elevated fat content and shortened life span. Employing a quantitative RT-PCR screen, we found that nhr-49 influenced the expression of 13 genes involved in energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage, modulating pathways that control the consumption of fat and maintain a normal balance of fatty acid saturation. We found that the two phenotypes of the nhr-49 knockout were linked to distinct pathways and were separable: The high-fat phenotype was due to reduced expression of enzymes in fatty acid beta-oxidation, and the shortened adult life span resulted from impaired expression of a stearoyl-CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism.

  1. The cyanobacteria derived toxin Beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Banack, Sandra Anne; Caller, Tracie A; Stommel, Elijah W

    2010-12-01

    There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer's disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.

  2. Beta-methyl substitution of cyclohexylalanine in Dmt-Tic-Cha-Phe peptides results in highly potent delta opioid antagonists.

    Science.gov (United States)

    Tóth, Géza; Ioja, Eniko; Tömböly, Csaba; Ballet, Steven; Tourwé, Dirk; Péter, Antal; Martinek, Tamás; Chung, Nga N; Schiller, Peter W; Benyhe, Sándor; Borsodi, Anna

    2007-01-25

    The opioid peptide TIPP (H-Tyr-Tic-Phe-Phe-OH, Tic:1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) was substituted with Dmt (2',6'-dimethyltyrosine) and a new unnatural amino acid, beta-MeCha (beta-methyl-cyclohexylalanine). This double substitution led to a new series of opioid peptides displaying subnanomolar delta antagonist activity and mu agonist or antagonist properties depending on the configuration of the beta-MeCha residue. The most promising analog, H-Dmt-Tic-(2S,3S)-beta-MeCha-Phe-OH was a very selective delta antagonist both in the mouse vas deferens (MVD) assay (Ke = 0.241 +/- 0.05 nM) and in radioligand binding assay (K i delta = 0.48 +/- 0.05 nM, K i mu/K i delta = 2800). The epimeric peptide H-Dmt-Tic-(2S,3R)-beta-MeCha-Phe-OH and the corresponding peptide amide turned out to be mixed partial mu agonist/delta antagonists in the guinea pig ileum and MVD assays. Our results constitute further examples of the influence of Dmt and beta-methyl substitution as well as C-terminal amidation on the potency, selectivity, and signal transduction properties of TIPP related peptides. Some of these compounds represent valuable pharmacological tools for opioid research.

  3. Analysis of some metabolites of organic solvents in urine by high-performance liquid chromatography with beta-cyclodextrin.

    Science.gov (United States)

    Moon, D H; Paik, N W; Shim, Y B

    1997-07-04

    Chromatographic separation of the metabolites derived from toluene, ethylbenzene, styrene and xylene was carried out on untreated urine samples from factory workers. The elution sequence was as follows: phenylglyoxilic acid, 3-hydroxy-2-butanone, hippuric acid, o-methylhippuric acid, p-methylhippuric acid, m-methylhippuric acid, p-cresol, m-cresol and o-cresol. The stability constants (K(G)) of cresol and methylhippuric acid derivatives were evaluated. The capacity factor (k'), selectivity factor (alpha) and resolution (Rs) are described with a variety of mobile phases containing beta-cyclodextrin (beta-CD). The optimum concentration ratio of ethanol-water-acetic acid-beta-CD was determined to be 20:80:0.3:1.4%. Under these conditions, k' values of the five metabolites were 2

  4. Effects of heavy metal accumulation on the midgut gland in a terrestrial isopod, Porcellio scaber

    Energy Technology Data Exchange (ETDEWEB)

    Szlavecz, K.; Komueves, L.G.; Gueth, S.

    1986-01-01

    The effects of lead and cadmium on the lysosomal enzyme activity, the protein content, and the ultrastructure of the midgut gland, which plays a central role in the metabolism of isopods, were studied. Hornbeam litter was sprayed with Pb acetate or Cd chloride solutions of different concentrations. The animals were fed with the contaminated leaf litter for one or two months. Leaf litter sprayed with distilled water served as control. X-ray fluorescence analysis showed considerable heavy metal accumulation in the whole body of the experimental animals. Total protein content of the midgut gland of the treated isopods was approximately 60% less than that of the controls. However, the total activities of the lysosomal enzymes (acid phosphatase, acid ..beta..-galactosidase, acid glucosidase) were not affected by the treatments, meaning, that specific activities of these enzymes increased. Electron microscopic investigation of the midgut gland revealed characteristic ultrastructural changes in the different cell types. The amount of glycogen and the number of lipid droplets and secretory granules decreased, whereas an increase in the number of autophagic vacuoles and large secondary lysosomes was observed. The study indicates, that heavy metals ingested with food are not only stored in the midgut gland, but they influence the ultrastructure and functions of its cells, as well.

  5. Suppression of fat deposition in broiler chickens by (-)-hydroxycitric acid supplementation: A proteomics perspective

    Science.gov (United States)

    Peng, Mengling; Han, Jing; Li, Longlong; Ma, Haitian

    2016-09-01

    (-)-Hydroxycitric acid (HCA) suppresses fatty acid synthesis in animals, but its biochemical mechanism in poultry is unclear. This study identified the key proteins associated with fat metabolism and elucidated the biochemical mechanism of (-)-HCA in broiler chickens. Four groups (n = 30 each) received a diet supplemented with 0, 1000, 2000 or 3000 mg/kg (-)-HCA for 4 weeks. Of the differentially expressed liver proteins, 40 and 26 were identified in the mitochondrial and cytoplasm respectively. Pyruvate dehydrogenase E1 components (PDHA1 and PDHB), dihydrolipoyl dehydrogenase (DLD), aconitase (ACO2), a-ketoglutarate dehydrogenase complex (DLST), enoyl-CoA hydratase (ECHS1) and phosphoglycerate kinase (PGK) were upregulated, while NADP-dependent malic enzyme (ME1) was downregulated. Biological network analysis showed that the identified proteins were involved in glycometabolism and lipid metabolism, whereas PDHA1, PDHB, ECHS1, and ME1 were identified in the canonical pathway by Ingenuity Pathway Analysis. The data indicated that (-)-HCA inhibited fatty acid synthesis by reducing the acetyl-CoA supply, via promotion of the tricarboxylic acid cycle (upregulation of PDHA1, PDHB, ACO2, and DLST expression) and inhibition of ME1 expression. Moreover, (-)-HCA promoted fatty acid beta-oxidation by upregulating ECHS1 expression. These results reflect a biochemically relevant mechanism of fat reduction by (-)-HCA in broiler chickens.

  6. Bezafibrate mildly stimulates ketogenesis and fatty acid metabolism in hypertriglyceridemic subjects.

    Science.gov (United States)

    Tremblay-Mercier, Jennifer; Tessier, Daniel; Plourde, Mélanie; Fortier, Mélanie; Lorrain, Dominique; Cunnane, Stephen C

    2010-07-01

    Our objective was to determine whether bezafibrate, a hypotriglyceridemic drug and peroxisome proliferator-activated receptor (PPAR)-alpha agonist, is ketogenic and increases fatty acid oxidation in humans. We measured fatty acid metabolism and ketone levels in 13 mildly hypertriglycemic adults (67 +/- 11 years old) during 2 metabolic study days lasting 6 h, 1 day before and 1 day after bezafibrate (400 mg of bezafibrate per day for 12 weeks). beta-Hydroxybutyrate, triglycerides, free fatty acids, fatty acid profiles, insulin, and glucose were measured in plasma, and fatty acid beta-oxidation was measured in breath after an oral 50-mg dose of the fatty acid tracer [U-(13)C]linoleic acid. As expected, 12 weeks on bezafibrate decreased plasma triglycerides by 35%. Bezafibrate tended to raise postprandial beta-hydroxybutyrate, an effect that was significant after normalization to the fasting baseline values (p = 0.03). beta-Oxidation of [U-(13)C]linoleic acid increased by 30% (p = 0.03) after treatment. On the metabolic study day after bezafibrate treatment, postprandial insulin decreased by 26% (p = 0.01), and glucose concentrations were lower 2 to 5 h postprandially. Thus, in hypertriglyceridemic individuals, bezafibrate is mildly ketogenic and significantly changes fatty acid metabolism, effects that may be linked to PPARalpha stimulation and to moderately improved glucose metabolism.

  7. Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.

    Science.gov (United States)

    Ciavardelli, Domenico; Piras, Fabrizio; Consalvo, Ada; Rossi, Claudia; Zucchelli, Mirco; Di Ilio, Carmine; Frazzini, Valerio; Caltagirone, Carlo; Spalletta, Gianfranco; Sensi, Stefano L

    2016-07-01

    Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD.

  8. Amino acid preference against beta sheet through allowing backbone hydration enabled by the presence of cation

    CERN Document Server

    Sharley, John N

    2016-01-01

    It is known that steric blocking by peptide sidechains of hydrogen bonding, HB, between water and peptide groups, PGs, in beta sheets accords with an amino acid intrinsic beta sheet preference. The present observations with Quantum Molecular Dynamics, QMD, simulation with quantum mechanical treatment of every water molecule solvating a beta sheet that would be transient in nature suggest that this steric blocking is not applicable in a hydrophobic region unless a cation is present, so that the amino acid beta sheet preference due to this steric blocking is only effective in the presence of a cation. We observed backbone hydration in a polyalanine and to a lesser extent polyvaline alpha helix without a cation being present, but a cation could increase the strength of these HBs. Parallel beta sheets have a greater tendency than antiparallel beta sheets of equivalent small size to retain regular structure in solvated QMD, and a 4 strand 4 inter-PG HB chain parallel beta sheet was used. Stability was reinforced b...

  9. The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Elijah W. Stommel

    2010-12-01

    Full Text Available There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis. The non-protein amino acid beta-N-methylamino-L-alanine (BMAA was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.

  10. The Effect of Aqueous Extract of Cinnamon on the Metabolome of Plasmodium falciparum Using 1HNMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Shirin Parvazi

    2016-01-01

    Full Text Available Malaria is responsible for estimated 584,000 deaths in 2013. Researchers are working on new drugs and medicinal herbs due to drug resistance that is a major problem facing them; the search is on for new medicinal herbs. Cinnamon is the bark of a tree with reported antiparasitic effects. Metabonomics is the simultaneous study of all the metabolites in biological fluids, cells, and tissues detected by high throughput technology. It was decided to determine the mechanism of the effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum in vitro using 1HNMR spectroscopy. Prepared aqueous extract of cinnamon was added to a culture of Plasmodium falciparum 3D7 and its 50% inhibitory concentration determined, and, after collection, their metabolites were extracted and 1HNMR spectroscopy by NOESY method was done. The spectra were analyzed by chemometric methods. The differentiating metabolites were identified using Human Metabolome Database and the metabolic cycles identified by Metaboanalyst. 50% inhibitory concentration of cinnamon on Plasmodium falciparum was 1.25 mg/mL with p<0.001. The metabolites were identified as succinic acid, glutathione, L-aspartic acid, beta-alanine, and 2-methylbutyryl glycine. The main metabolic cycles detected were alanine and aspartame and glutamate pathway and pantothenate and coenzyme A biosynthesis and lysine biosynthesis and glutathione metabolism, which are all important as drug targets.

  11. Glycerophosphoglycerol, Beta-Alanine, and Pantothenic Acid as Metabolic Companions of Glycolytic Activity and Cell Migration in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Antje Hutschenreuther

    2013-11-01

    Full Text Available In cancer research, cell lines are used to explore the molecular basis of the disease as a substitute to tissue biopsies. Breast cancer in particular is a very heterogeneous type of cancer, and different subgroups of cell lines have been established according to their genomic profiles and tumor characteristics. We applied GCMS metabolite profiling to five selected breast cancer cell lines and found this heterogeneity reflected on the metabolite level as well. Metabolite profiles of MCF-7 cells belonging to the luminal gene cluster proved to be more different from those of the basal A cell line JIMT-1 and the basal B cell lines MDA-MB-231, MDA-MB-435, and MDA-MB-436 with only slight differences in the intracellular metabolite pattern. Lactate release into the cultivation medium as an indicator of glycolytic activity was correlated to the metabolite profiles and physiological characteristics of each cell line. In conclusion, pantothenic acid, beta-alanine and glycerophosphoglycerol appeared to be related to the glycolytic activity designated through high lactate release. Other physiological parameters coinciding with glycolytic activity were high glyoxalase 1 (Glo1 and lactate dehydrogenase (LDH enzyme activity as well as cell migration as an additional important characteristic contributing to the aggressiveness of tumor cells. Metabolite profiles of the cell lines are comparatively discussed with respect to known biomarkers of cancer progression.

  12. Structural studies of MFE-1: the 1.9 A crystal structure of the dehydrogenase part of rat peroxisomal MFE-1.

    Science.gov (United States)

    Taskinen, Jukka P; Kiema, Tiila R; Hiltunen, J Kalervo; Wierenga, Rik K

    2006-01-27

    The 1.9 A structure of the C-terminal dehydrogenase part of the rat peroxisomal monomeric multifunctional enzyme type 1 (MFE-1) has been determined. In this construct (residues 260-722 and referred to as MFE1-DH) the N-terminal hydratase part of MFE-1 has been deleted. The structure of MFE1-DH shows that it consists of an N-terminal helix, followed by a Rossmann-fold domain (domain C), followed by two tightly associated helical domains (domains D and E), which have similar topology. The structure of MFE1-DH is compared with the two known homologous structures: human mitochondrial 3-hydroxyacyl-CoA dehydrogenase (HAD; sequence identity is 33%) (which is dimeric and monofunctional) and with the dimeric multifunctional alpha-chain (alphaFOM; sequence identity is 28%) of the bacterial fatty acid beta-oxidation alpha2beta2-multienzyme complex. Like MFE-1, alphaFOM has an N-terminal hydratase part and a C-terminal dehydrogenase part, and the structure comparisons show that the N-terminal helix of MFE1-DH corresponds to the alphaFOM linker helix, located between its hydratase and dehydrogenase part. It is also shown that this helix corresponds to the C-terminal helix-10 of the hydratase/isomerase superfamily, suggesting that functionally it belongs to the N-terminal hydratase part of MFE-1.

  13. Ketone body metabolism and its defects.

    Science.gov (United States)

    Fukao, Toshiyuki; Mitchell, Grant; Sass, Jörn Oliver; Hori, Tomohiro; Orii, Kenji; Aoyama, Yuka

    2014-07-01

    Acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), the two main ketone bodies of humans, are important vectors of energy transport from the liver to extrahepatic tissues, especially during fasting, when glucose supply is low. Blood total ketone body (TKB) levels should be evaluated in the context of clinical history, such as fasting time and ketogenic stresses. Blood TKB should also be evaluated in parallel with blood glucose and free fatty acids (FFA). The FFA/TKB ratio is especially useful for evaluation of ketone body metabolism. Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) deficiency and HMG-CoA lyase (HL) deficiency. mHS deficiency should be considered in non-ketotic hypoglycemia if a fatty acid beta-oxidation defect is suspected, but cannot be confirmed. Patients with HL deficiency can develop hypoglycemic crises and neurological symptoms even in adolescents and adults. Succinyl-CoA-3-oxoacid CoA transferase (SCOT) deficiency and beta-ketothiolase (T2) deficiency are two defects in ketolysis. Permanent ketosis is pathognomonic for SCOT deficiency. However, patients with "mild" SCOT mutations may have nonketotic periods. T2-deficient patients with "mild" mutations may have normal blood acylcarnitine profiles even in ketoacidotic crises. T2 deficient patients cannot be detected in a reliable manner by newborn screening using acylcarnitines. We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy.

  14. Rapid detection of medium chain acyl-CoA dehydrogenase gene mutations by non-radioactive, single strand conformation polymorphism minigels.

    Science.gov (United States)

    Iolascon, A; Parrella, T; Perrotta, S; Guardamagna, O; Coates, P M; Sartore, M; Surrey, S; Fortina, P

    1994-07-01

    Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is a common inherited metabolic disorder affecting fatty acid beta oxidation. Identification of carriers is important since the disease can be fatal and is readily treatable once diagnosed. Twelve molecular defects have been identified in the MCAD gene; however, a single highly prevalent mutation, A985G, accounts for > 90% of mutant alleles in the white population. In order to facilitate the molecular diagnosis of MCAD deficiency, oligonucleotide primers were designed to amplify the exon regions encompassing the 12 mutations enzymatically, and PCR products were then screened with a single strand conformation polymorphism (SSCP) based method. Minigels were used allowing much faster run times, and silver staining was used after gel electrophoresis to eliminate the need for radioisotopic labelling strategies. Our non-radioactive, minigel SSCP approach showed that normals can be readily distinguished from heterozygotes and homozygotes for all three of the 12 known MCAD mutations which were detected in our sampling of 48 persons. In addition, each band pattern is characteristic for a specific mutation, including those mapping in the same PCR product like A985G and T1124C. When necessary, the molecular defect was confirmed using either restriction enzyme digestion of PCR products or by direct DNA sequence analysis or both. This rapid, non-radioactive approach can become routine for molecular diagnosis of MCAD deficiency and other genetic disorders.

  15. Drug-induced hyperkalemia.

    Science.gov (United States)

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  16. Biotechnology and pharmacological evaluation of Indian vegetable crop Lagenaria siceraria: an overview.

    Science.gov (United States)

    Roopan, Selvaraj Mohana; Devi Rajeswari, V; Kalpana, V N; Elango, G

    2016-02-01

    Bottle gourd (Lagenaria siceraria) belongs to the family Cucurbitaceae, which comprises about 118 genera and 825 species. It is an important vegetable crop of India, and its production is influenced by a number of factors viz., environmental, nutritional, cultural operation and use of plant growth regulators. Since, bottle gourd belongs to a medicinal family, it plays a major role in the treatment of several diseases related to the skin and heart. There are several organic chemical compounds including vitamin B complex, pectin, dietary soluble fibres, ascorbic acid, beta-carotene, amino acids and minerals which have been isolated from this species. Therefore, the bottle gourd is considered to have a great impact on therapeutic health benefits. Due to drastic industrialization and urbanization, most of the human beings are facing several ill effects which may lead to death at extreme cases. Hence, the major research area was said to be nanotechnology. Taking into consideration, we have combined nanotechnology field with waste source in the name of green synthesis and planned to cure several diseases, as most of the researchers focused their work on this and succeeded too. The present study is a complete review of L. siceraria that covers the ethnomedical uses, chemical constituents, and pharmacological profile. This study is mainly focused on the antibacterial, hepatoprotective, diuretic and anthelminthic activities.

  17. Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids.

    Science.gov (United States)

    Bhattarai, Sushila; Tran, Van H; Duke, Colin C

    2007-11-30

    The degradation kinetics of [6]-gingerol and [6]-shogaol were investigated in simulated gastric (pH 1) and intestinal (pH 7.4) fluids at 37 degrees C. Degradation products were quantitatively determined by HPLC (Lichrospher 60 RP select B column, 5 microm, 125 mm x 4 mm; mobile phase: methanol-water-acetic acid (60:39:1 v/v); flow rate: 0.6 ml/min; detection UV: 280 nm). In simulated gastric fluid (SGF) [6]-gingerol and [6]-shogaol underwent first-order reversible dehydration and hydration reactions to form [6]-shogaol and [6]-gingerol, respectively. The degradation was catalyzed by hydrogen ions and reached equilibrium at approximately 200 h. In simulated intestinal fluid (SIF) both [6]-gingerol and [6]-shogaol showed insignificant interconversion between one another. Addition of amino acids glycine, 3-amino propionic acid (beta-alanine) and gamma-amino butyric acid (GABA), and ammonium acetate at a range of concentrations of 0.05-0.5mM had no effect on the rate of degradation of [6]-shogaol in SGF and 0.1M HCl solution. However, at exceedingly high concentration (0.5M) of ammonium acetate and glycine, significant amounts of [6]-shogaol ammonia and glycine adducts were detected. The degradation profile of [6]-gingerol and [6]-shogaol under simulated physiological conditions reported in this study will provide insight into the stability of these compounds when administered orally.

  18. A microdeletion at 12q24.31 can mimic beckwith-wiedemann syndrome neonatally.

    Science.gov (United States)

    Baple, E; Palmer, R; Hennekam, R C M

    2010-02-01

    We report on a patient who was initially suspected to have Beckwith-Wiedemann syndrome because of recurrent neonatal hypoglycaemias, macroglossia and overgrowth, but in whom no 11p15 abnormality could be found. Follow-up showed continued overgrowth and disturbed glucose homeostasis, a marked developmental delay, and severe behavioural problems especially caused by anxieties. Array comparative genomic hybridization analysis showed a de novo 12q24.31 interstitial deletion, which was confirmed by fluorescence in situ hybridization. The deleted region contains amongst others: HNF1 homeobox A (HNF1A) which is important for the regulation of gene expression in the liver and involved in maturity-onset diabetes of the young type 3 and insulin resistance; acyl-CoA dehydrogenase short chain (ACADS) which encodes an enzyme important in mitochondrial fatty acid beta-oxidation and can cause short-chain acyl-CoA dehydrogenese (SCAD) deficiency, and purinergic receptor P2X7 (P2RX7) which encodes a ligand-gated ion channel, and of which polymorphisms are found with increased frequency in patients with psychiatric disorders, especially anxieties. We conclude the present patient has a hitherto undescribed contiguous gene syndrome, which can initially resemble Beckwith-Wiedemann syndrome.

  19. Biosynthesis of the Caenorhabditis elegans dauer pheromone.

    Science.gov (United States)

    Butcher, Rebecca A; Ragains, Justin R; Li, Weiqing; Ruvkun, Gary; Clardy, Jon; Mak, Ho Yi

    2009-02-10

    To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human d-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state.

  20. Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations.

    Science.gov (United States)

    Spiekerkoetter, Ute; Eeds, Angela; Yue, Zou; Haines, Jonathan; Strauss, Arnold W; Summar, Marshall

    2002-12-01

    The mitochondrial trifunctional protein (TFP) is an enzyme complex of the fatty acid beta-oxidation cycle composed of an alpha- and a beta-subunit. The two encoding genes are located in the same region on chromosome 2 (2p23). TFP deficiency due to either alpha- or beta-subunit mutations is characterized by mutational and phenotypic heterogeneity with severe, early-onset, cardiac forms and milder, later-onset, myopathic phenotypes. In two unrelated patients with lethal TFP deficiency, we delineated apparently homozygous alpha-subunit mutations that were present in heterozygous form in both mothers, but not in either biological father. We performed a microsatellite repeat analysis of both patients and their parents using seven chromosome 2-specific polymorphic DNA markers and four nonchromosome 2 markers. In both patients, two chromosome 2-specific markers demonstrated maternal isodisomy of chromosome 2. The other five chromosome 2-specific markers were noninformative in each patient. Inheritance of alleles from chromosomes 4, 5, and 7 was consistent with paternity. These results explain the apparently anomalous pattern of transmission. Six of our 12 known TFP-deficient patients with alpha-subunit mutations have disease due to homozygous changes and two of them via the mechanism of uniparental disomy (UPD) (16.7%). For very rare autosomal recessive diseases, UPD may represent a common mechanism. This study emphasizes the need to confirm mutations in parents whenever possible. TFP deficiency is another disorder that has become manifest due to isodisomy of chromosome 2. This information will impact genetic counseling for these families, reducing greatly the 25% risk normally used for recessive disorders.

  1. Analysis of β-N-methylamino-L-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry

    Science.gov (United States)

    2014-01-01

    Over the last decade the amino acid beta-N-methylamino-L-alanine (BMAA) has come under intense scrutiny. International laboratory and epidemiological research continues to support the hypothesis that environmental exposure to BMAA (e.g., through dietary practices, water supply) can promote the risk of various neurodegenerative diseases. A wide variety of cyanobacteria spp. have previously been reported to produce BMAA, with production levels dependent upon species, strain and environmental conditions. Since spirulina (Arthrospira spp.) is a member of the cyanobacteria phylum frequently consumed via dietary supplements, the presence of BMAA in such products may have public health implications. In the current work, we have analyzed ten spirulina-containing samples for the presence of BMAA; six pure spirulina samples from two separate raw materials suppliers, and four commercially-available multi-ingredient products containing 1.45 g of spirulina per 8.5 g serving. Because of controversy surrounding the measurement of BMAA, we have used two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods: one based on reversed phase LC (RPLC) with derivatization and the other based on hydrophilic interaction LC (HILIC). Potential matrix effects were corrected for by internal standardization using a stable isotope labeled BMAA standard. BMAA was not detected at low limits of detection (80 ng/g dry weight) in any of these product samples. Although these results are reassuring, BMAA analyses should be conducted on a wider sample selection and, perhaps, as part of ongoing spirulina production quality control testing and specifications. PMID:25120905

  2. Hepatic Proteomic Responses in Marine Medaka ( Oryzias melastigma ) Chronically Exposed to Antifouling Compound Butenolide [5-octylfuran-2(5H)-one] or 4,5-Dichloro-2- N -Octyl-4-Isothiazolin-3-One (DCOIT)

    KAUST Repository

    Chen, Lianguo

    2015-02-03

    The pollution of antifoulant SeaNine 211, with 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) as active ingredient, in coastal environment raises concerns on its adverse effects, including endocrine disruption and impairment of reproductive function in marine organisms. In the present study, we investigated the hepatic protein expression profiles of both male and female marine medaka (Oryzias melastigma) exposed to low concentrations of DCOIT at 2.55 mu g/L (0.009 mu M) or butenolide, a promising antifouling agent, at 2.31 mu g/L (0.012 mu M) for 28 days. The results showed that proteins involved in phase I (CYP450 enzyme) metabolism, phase II (UDPGT and GST) conjugation as well as mobilization of retinoid storage, an effective nonenzymatic antioxidant, were consistently up-regulated, possibly facilitating the accelerated detoxification of butenolide. Increased synthesis of bile acid would promote the immediate excretion of butenolide metabolites. Activation of fatty acid beta-oxidation and ATP synthesis were consistent with elevated energy consumption for butenolide degradation and excretion. However, DCOIT did not significantly affect the detoxification system of male medaka, but induced a marked increase of vitellogenin (VTG) by 2.3-fold in the liver of male medaka, suggesting that there is estrogenic activity of DCOIT in endocrine disruption. Overall, this study identified the molecular mechanisms and provided sensitive biomarkers characteristic of butenolide and DCOIT in the liver of marine medaka. The low concentrations of butenolide and DCOIT used in the exposure regimes highlight the needs for systematic evaluation of their environmental risk. In addition, the potent estrogenic activity of DCOIT should be considered in the continued applications of SeaNine 211.

  3. Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hae; Jun, Hee-jin; Hoang, Minh-Hien; Jia, Yaoyao [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Han, Xiang Hua [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Dong-Ho [Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Hak-Ju [Division of Green Business Management, Department of Forest Resources Utilization, Korean Forest Research Institute, Seoul 130-712 (Korea, Republic of); Hwang, Bang Yeon, E-mail: byhwang@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Sung-Joon, E-mail: junelee@korea.ac.kr [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Catalposide is a novel ligand for PPAR{alpha}. Black-Right-Pointing-Pointer Cell stimulated with catalposide improved fatty acid uptake, regulated target genes in fatty acid {beta}-oxidation and synthesis. Black-Right-Pointing-Pointer Catalposdie reduces hepatic triacylglycerides. Black-Right-Pointing-Pointer Theses demonstrate catalposide could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: Peroxisome proliferator-activated receptor-alpha (PPAR{alpha}) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPAR{alpha} agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPAR{alpha} agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPAR{alpha}. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (P < 0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPAR{alpha} via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

  4. Effects of breeder hen age and dietary L-carnitine on progeny embryogenesis.

    Science.gov (United States)

    Peebles, E D; Kidd, M T; McDaniel, C D; Tanksley, J P; Parker, H M; Corzo, A; Woodworth, J C

    2007-06-01

    1. Ross 308 broiler breeder hens were given diets containing 0 or 25 mg L-carnitine/kg (8 replications per treatment) from 21 weeks of age. 2. Hens were inseminated with semen from Ross broiler breeder males. In a common facility, subsequent progeny hatchability and embryonic mortality at 25, 30, 32, and 38 weeks of breeder age were evaluated. 3. Subsequent egg component weights, incubational egg water loss, progeny embryo growth, and embryo, yolk sac and liver composition through 18 d of incubation at 27, 32, and 38 weeks of breeder age were evaluated. 4. Calculated additions of L-carnitine were in agreement with analysed contents of 3.5 and 31.1 mg free L-carnitine/kg of diet, respectively, and total L-carnitine concentrations increased by 48.6, 21.7, and 10.0% in 0-d yolk, 18-d yolk sac, and 18-d liver samples, respectively, due to the addition of dietary L-carnitine. 5. Supplemental L-carnitine resulted in increased (0.6%) relative 0-d egg yolk weight across weeks 27, 32, and 38, and reduced (0.38%) 18-d yolk sac palmitoleic acid concentration at week 27 without altering embryogenesis. 6. In conclusion, dietary L-carnitine (25 mg/kg of the diet) was deposited in the yolks of broiler breeder hens and was subsequently transferred to the embryonic liver via yolk sac absorption through 18 d of incubation. Furthermore, dietary L-carnitine supplementation increased ovarian follicle yolk deposition in 27-, 32-, and 38-week-old breeder hens, and influenced yolk sac fatty acid beta-oxidation in embryos from 27-week-old breeder hens causing yolk sac palmitoleic acid concentrations to be reduced by 18 d of incubation.

  5. Modeling of olive oil degradation and oleic acid inhibition during chemostat and batch cultivation of Bacillus thermoleovorans IHI-91.

    Science.gov (United States)

    Becker, P; Märkl, H

    2000-12-20

    Olive oil degradation by the thermophilic lipolytic strain Bacillus thermoleovorans IHI-91 in chemostat and batch culture was modeled to obtain a general understanding of the underlying principles and limitations of the process and to quantify its stoichiometry. Chemostat experiments with olive oil as the sole carbon source were successfully described using the Monod chemostat model extended by terms for maintenance requirements and wall growth. Maintenance requirements and biomass yield coefficients were in the range reported for mesophiles. For a chemostat experiment at D = 0.3 h(-1) the model was validated up to an olive oil feed concentration of about 3.0 g L(-1) above which an inhibitory effect occurred. Further analysis showed that the liberated oleic acid is the main cause for this inhibition. Using steady-state oleic acid concentrations measured in chemostat experiments with olive oil as substrate it was possible to derive a kinetic expression for oleic acid utilization, showing that a concentration of 430 mg L(-1) leads to a complete growth inhibition. Oleic acid accumulation observed during batch fermentations can be predicted using a model involving growth-associated lipase production and olive oil hydrolysis. Simulations confirmed that this accumulation is the cause for the sudden growth cessation occurring in batch fermentations with higher olive oil start concentrations. Further, an oscillatory behavior, as observed in some chemostat experiments, can also be predicted using the latter model. This work clearly demonstrates that thermophilic lipid degradation by Bacillus thermoleovorans IHI-91 is limited by long-chain fatty acid beta-oxidation rather than oil hydrolysis.

  6. Supercritical Fluid Extraction of Plutonium and Americium from Soil

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Robert Vincent; Mincher, Bruce Jay

    2002-08-01

    Supercritical fluid extraction (SFE) of plutonium and americium from soil was successfully demonstrated using supercritical fluid carbon dioxide solvent augmented with organophosphorus and beta-diketone complexants. Spiked Idaho soils were chemically and radiologically characterized, then extracted with supercritical fluid carbon dioxide at 2,900 psi and 65°C containing varying concentrations of tributyl phosphate (TBP) and thenoyltrifluoroacetone (TTA). A single 45 minute SFE with 2.7 mol% TBP and 3.2 mol% TTA provided as much as 88% ± 6.0 extraction of americium and 69% ± 5.0 extraction of plutonium. Use of 5.3 mol% TBP with 6.8 mol% of the more acidic beta-diketone hexafluoroacetylacetone (HFA) provided 95% ± 3.0 extraction of americium and 83% ± 5.0 extraction of plutonium in a single 45 minute SFE at 3,750 psi and 95°C. Sequential chemical extraction techniques were used to chemically characterize soil partitioning of plutonium and americium in pre-SFE soil samples. Sequential chemical extraction techniques demonstrated that spiked plutonium resides primarily (76.6%) in the sesquioxide fraction with minor amounts being absorbed by the oxidizable fraction (10.6%) and residual fractions (12.8%). Post-SFE soils subjected to sequential chemical extraction characterization demonstrated that 97% of the oxidizable, 78% of the sesquioxide and 80% of the residual plutonium could be removed using SFE. These preliminary results show that SFE may be an effective solvent extraction technique for removal of actinide contaminants from soil.

  7. Quantitative Proteomic Analysis Reveals that Antioxidation Mechanisms Contribute to Cold Tolerance in Plantain (Musa paradisiaca L.;ABB Group) Seedlings

    Institute of Scientific and Technical Information of China (English)

    Qiaosong Yang; Junhua Wu; Chunyu Li; Yuerong Wei; Ou Sheng; Chunhua Hu; Ruibin Kuang

    2012-01-01

    Banana and its close relative,plantain are globally important crops and there is of considerable interest in optimizing their cultivation.Plantain has superior cold tolerance compared to banana and a thorough understanding of the molecular mechanisms and responses of plantain to cold stress has great potential value for developing cold tolerant banana cultivars.In this study,we used iTRAQ-based comparative proteomic analysis to investigate the temporal responses of plantain to cold stress.Plantain seedlings were exposed for 0,6 and 24 h of cold stress at 8℃ and subsequently allowed to recover for 24 h at 28℃.A total of 3,477 plantain proteins were identified,of which 809 showed differential expression from the three treatments.The majority of differentially expressed proteins were predicted to be involved in oxidation-reduction,including oxylipin biosynthesis,while others were associated with photosynthesis,photorespiration and several primary metabolic processes,such as carbohydrate metabolic process and fatty acid beta-oxidation.Western blot analysis and enzyme activity assays were performed on 7 differentially expressed,cold-response candidate plantain proteins in order to validate the proteomics data.Similar analyses of the 7 candidate proteins were performed in cold-sensitive banana to examine possible functional conservation and to compare the results to equivalent responses between the two species.Consistent results were achieved by Western blot and enzyme activity assays,demonstrating that the quantitative proteomics data collected in this study are reliable.Our results suggest that an increase of antioxidant capacity through adapted ROS scavenging capability,reduced production of ROS and decreased lipid peroxidation contribute to molecular mechanisms for the higher cold tolerance in plantain.To the best of our knowledge,this is the first report of a global investigation on molecular responses of plantain to cold stress by proteomic analysis.

  8. 线粒体功能在骨骼肌胰岛素抵抗中的作用%The role of mitochondrial function in skeletal muscle insulin resistance

    Institute of Scientific and Technical Information of China (English)

    张克莹; 都健

    2011-01-01

    Mitochondria are the organelles which can provide energy to carry out various life activities.More and more evidences have shown that mitochondrial dysfunction is closely related to skeletal muscle insulin resistance.The mechanism may be the dysfunction of fatty acid beta oxidation,caused by the damage of mitochondria thus affecting insulin receptor signaling pathways,and finally resulting in the occurrence of insulin resistance.In addition,dysregulation of mitochondria fusion protein and gene expression can cause abnormal mitochondria dynamics or downregulation of membrane potential,finally leads to insulin resistance.The current research on mitochondrial dysfunction,especially oxidative stress will provide new ideas for the treatment of type 2 diabetes.%线粒体是提供细胞进行各种生命活动所需能量的细胞器,越来越多的证据表明,线粒体功能与骨骼肌胰岛素抵抗状态密切相关,这种机制可能因为线粒体功能损伤引发脂肪酸β-氧化功能障碍,最终影响胰岛素受体后信号转导通路而致胰岛素抵抗的发生;也可因为线粒体融合蛋白或基因调控受损造成线粒体动力学异常或膜电位下降,造成胰岛素抵抗.目前对于线粒体功能障碍的研究,尤其是氧化应激机制的研究,可为治疗2型糖尿病提供新的思路.

  9. AMP-activated protein kinase (AMPK mediates nutrient regulation of thioredoxin-interacting protein (TXNIP in pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Maayan Shaked

    Full Text Available Thioredoxin-interacting protein (TXNIP regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP. Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment

  10. Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships.

    Directory of Open Access Journals (Sweden)

    Pranali P Pathare

    Full Text Available Mammalian nuclear receptors broadly influence metabolic fitness and serve as popular targets for developing drugs to treat cardiovascular disease, obesity, and diabetes. However, the molecular mechanisms and regulatory pathways that govern lipid metabolism remain poorly understood. We previously found that the Caenorhabditis elegans nuclear hormone receptor NHR-49 regulates multiple genes in the fatty acid beta-oxidation and desaturation pathways. Here, we identify additional NHR-49 targets that include sphingolipid processing and lipid remodeling genes. We show that NHR-49 regulates distinct subsets of its target genes by partnering with at least two other distinct nuclear receptors. Gene expression profiles suggest that NHR-49 partners with NHR-66 to regulate sphingolipid and lipid remodeling genes and with NHR-80 to regulate genes involved in fatty acid desaturation. In addition, although we did not detect a direct physical interaction between NHR-49 and NHR-13, we demonstrate that NHR-13 also regulates genes involved in the desaturase pathway. Consistent with this, gene knockouts of these receptors display a host of phenotypes that reflect their gene expression profile. Our data suggest that NHR-80 and NHR-13's modulation of NHR-49 regulated fatty acid desaturase genes contribute to the shortened lifespan phenotype of nhr-49 deletion mutant animals. In addition, we observed that nhr-49 animals had significantly altered mitochondrial morphology and function, and that distinct aspects of this phenotype can be ascribed to defects in NHR-66- and NHR-80-mediated activities. Identification of NHR-49's binding partners facilitates a fine-scale dissection of its myriad regulatory roles in C. elegans. Our findings also provide further insights into the functions of the mammalian lipid-sensing nuclear receptors HNF4α and PPARα.

  11. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); The First Affiliated Hospital of Xiamen University, Xiamen (China); Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); Yu, Chundong, E-mail: cdyu@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China)

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  12. Adiponectin increases glucose-induced insulin secretion through the activation of lipid oxidation.

    Science.gov (United States)

    Patané, G; Caporarello, N; Marchetti, P; Parrino, C; Sudano, D; Marselli, L; Vigneri, R; Frittitta, L

    2013-12-01

    The expression of adiponectin receptors has been demonstrated in human and rat pancreatic beta cells, where globular (g) adiponectin rescues rat beta cells from cytokine and fatty acid-induced apoptosis. The aim of our study was to evaluate whether adiponectin has a direct effect on insulin secretion and the metabolic pathways involved. Purified human pancreatic islets and rat beta cells (INS-1E) were exposed (1 h) to g-adiponectin, and glucose-induced insulin secretion was measured. A significant increase in glucose-induced insulin secretion was observed in the presence of g-adiponectin (1 nmol/l) with respect to control cells in both human pancreatic islets (n = 5, p < 0.05) and INS-1E cells (n = 5, p < 0.001). The effect of globular adiponectin on insulin secretion was independent of AMP-dependent protein kinase (AMPK) activation or glucose oxidation. In contrast, g-adiponectin significantly increased oleate oxidation (n = 5, p < 0.05), and the effect of g-adiponectin (p < 0.001) on insulin secretion by INS-1E was significantly reduced in the presence of etomoxir (1 μmol/l), an inhibitor of fatty acid beta oxidation. g-Adiponectin potentiates glucose-induced insulin secretion in both human pancreatic islets and rat beta cells via an AMPK independent pathway. Increased fatty acid oxidation rather than augmented glucose oxidation is the mechanism responsible. Overall, our data indicate that, in addition to its anti-apoptotic action, g-adiponectin has another direct effect on beta cells by potentiating insulin secretion. Adiponectin, therefore, in addition to its well-known effect on insulin sensitivity, has important effects at the pancreatic level.

  13. Quantitative proteomic analysis reveals that antioxidation mechanisms contribute to cold tolerance in plantain (Musa paradisiaca L.; ABB Group) seedlings.

    Science.gov (United States)

    Yang, Qiao-Song; Wu, Jun-Hua; Li, Chun-Yu; Wei, Yue-Rong; Sheng, Ou; Hu, Chun-Hua; Kuang, Rui-Bin; Huang, Yong-Hong; Peng, Xin-Xiang; McCardle, James A; Chen, Wei; Yang, Yong; Rose, Jocelyn K C; Zhang, Sheng; Yi, Gan-Jun

    2012-12-01

    Banana and its close relative, plantain are globally important crops and there is considerable interest in optimizing their cultivation. Plantain has superior cold tolerance compared with banana and a thorough understanding of the molecular mechanisms and responses of plantain to cold stress has great potential value for developing cold tolerant banana cultivars. In this study, we used iTRAQ-based comparative proteomic analysis to investigate the temporal responses of plantain to cold stress. Plantain seedlings were exposed for 0, 6, and 24 h of cold stress at 8 °C and subsequently allowed to recover for 24 h at 28 °C. A total of 3477 plantain proteins were identified, of which 809 showed differential expression from the three treatments. The majority of differentially expressed proteins were predicted to be involved in oxidation-reduction, including oxylipin biosynthesis, whereas others were associated with photosynthesis, photorespiration, and several primary metabolic processes, such as carbohydrate metabolic process and fatty acid beta-oxidation. Western blot analysis and enzyme activity assays were performed on seven differentially expressed, cold-response candidate plantain proteins to validate the proteomics data. Similar analyses of the seven candidate proteins were performed in cold-sensitive banana to examine possible functional conservation, and to compare the results to equivalent responses between the two species. Consistent results were achieved by Western blot and enzyme activity assays, demonstrating that the quantitative proteomics data collected in this study are reliable. Our results suggest that an increase of antioxidant capacity through adapted ROS scavenging capability, reduced production of ROS, and decreased lipid peroxidation contribute to molecular mechanisms for the increased cold tolerance in plantain. To the best of our knowledge, this is the first report of a global investigation on molecular responses of plantain to cold stress by

  14. Hula Valley peat: review of chemical and geochemical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, S.; Ikan, R.; Agron, N.A.; Nissenbaum, A.

    1978-04-01

    In the Hula Valley, Israel, four layers of peat of Middle Pleistocene to Holocene age, interbedded with limnic clays and marls, are found above 300-m depth. The main detrital minerals are kaolinite, montmorillonite, and illite. Average elemental values of organic matter of dry peat are: C, 15-29 percent; H, 1.8-3 percent; N, 0.8-1.2 percent; S, 2.3-5 percent. The ash content (on dry basis) is 36-59 percent. The average calorific value ranges from 1670 to 3400 cal/g. Organic constituents isolated from the upper layer (Peat Horizon One) include: C/sub 12/ to C/sub 26/ fatty acids, ..beta..-sitosterol, ..beta..-sitostanol, friedelin and friedelanol, ceryl alcohol, a series of hydrocarbons, among them the polycyclic hydrocarbon, perylene, 13 amino acids and a series of polysaccharides of molecular weight in the range of 40,000. A detailed quantitative investigation of the distribution with depth in the top peat layer of the humic, fulvic, and hymatomelanic acids, as well as of the ..beta..-humus and humin, showed humin to be the dominant fraction of the organic matter. Its amount increases from 62 percent of the organic matter (by weight) at the surface to 70 to 90 percent at 2-m depth. The fulvic acid and polysaccharides show rapid decrease with depth, accompanied by concomitant increase in the ..beta..-humus. The humic acid increases with depth. Analysis of the peat organic fractions for carbon and hydrogen stable isotopes shows that with depth the difference in delta C/sup 13/ between the humic and fulvic acids disappears and the delta C/sup 13/ stabilizes at around -18 parts per thousand. The isotope data indicate the dynamic nature of the fulvic acid in the peat. The delta D values were around -60 parts per thousand, but the data are too meager for any firm conclusion.

  15. Liver transcriptome changes in zebrafish during acclimation to transport-associated stress.

    Directory of Open Access Journals (Sweden)

    Anusha K S Dhanasiri

    Full Text Available Liver plays a key role during the stress acclimation, and liver transcriptome analysis of shipped zebrafish could reveal the molecular adjustments that occur in the organ. Transcriptional changes in liver were analyzed with a 44 K oligo array using total RNA from fish prior to transport and during a mock transport process--immediately after packing (0 h, at 48 and 72 h. Large numbers of genes related to a variety of biological processes and pathways were regulated, mainly during transport (at 48/72 h. Immediately after packing, transcripts of genes related to both gluconeogenesis and glycolysis were induced. During transport, induction of gluconeogenesis-linked genes and reduction of glycolysis-related genes may be supporting the increase in blood glucose levels. Inhibition of genes involved in fatty acid beta-oxidation may be pointing to the poor ability of fish to utilize energy from fatty acids, under transport conditions. Genes involved in some of the mechanisms that regulate body ammonia were also affected. Even though genes associated with certain transaminases were inhibited in liver, sustained glutamate deamination may have led to high ammonia accumulation in liver/body. Enhanced levels of gene transcripts in ubiquitination and MAPK signalling cascade and reduced levels of gene transcripts related to ROS generation via peroxisomal enzymes as well as xenobiotic metabolism may be signifying the importance of such cellular and tissue responses to maintain homeostasis. Furthermore, transcripts connected with stress and thyroid hormones were also regulated. Moreover, suppression of genes related to specific immune components may be denoting the deleterious impact of transport on fish health. Thus, this study has revealed the complex molecular adjustments that occur in zebrafish when they are transported.

  16. [Three siblings with type 3 GM1-gangliosidosis--pathophysiology of dystonia and MRI findings].

    Science.gov (United States)

    Uyama, E; Terasaki, T; Owada, M; Naito, M; Araki, S

    1990-08-01

    GM1-gangliosidosis is a rare neurovisceral storage disease caused by an inherited deficiency of acid beta-galactosidase. The characteristic neurological feature of type 3 (adult or chronic) GM1-gangliosidosis is usually a slowly progressive dystonia with dysarthria due to predominant involvement of basal ganglia. About 20 adult patients with this disorder have been reported in the literature. However, there are no reports of 3 brothers with type 3 GM1-gangliosidosis, and MRI findings. Case 1 (proband): A 28-year-old man was hospitalized because of facial grimace, dysarthria, and generalized dystonia. He was born after normal pregnancy and delivery. His development was normal until 3 years of age when the difficulties of speaking and walking were noticed by his parents. These neurological abnormalities progressed slowly and facial grimace and dystonic movements occurred 7 years later. He could not walk at 22 years of age. On admission, he was bedridden with marked scoliosis and subluxation of the mandibule. The communication was possible only by pointing the words written on the board. Case 2: A 33-year-old man, elder brother of case 1, showed the similar neurological features and clinical course. Slit-lamp examination revealed corneal opacities which were located in the deep stroma. Case 3: A 33-year-old man, elder brother of case 1 or case 2. At age 10-11, he noted similar symptoms as case 1 or case 2. The severity of dystonia was milder than his brothers. A diagnosis of GM1-gangliosidosis in three patients was made on the basis of the following data.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

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    Vikrant Rachakonda

    Full Text Available BACKGROUND AND OBJECTIVES: While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH, the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. METHODS: This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. RESULTS: Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. CONCLUSION

  18. Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

    Science.gov (United States)

    Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.

    2009-01-01

    Amino acid analysis of a meteorite fragment of asteroid 2008 TC(sub 3) called Almahata Sitta was carried out using reverse-phase high-perfo rmance liquid chromatography coupled with UV fluorescence detection a nd time-of-flight mass spectrometry (HPLC-FD/ToF-MS) as part of a sam ple analysis consortium. HPLC analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to six-carbon aliph atic amino acids and one- to three carbon amines with abundances rang ing from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, Beta-amino-n-butyric acid (Beta-ABA), 2-amino-2- methylbutanoic acid (isovaline), and 2-aminopentanoic acid (no rvaline) in the meteorite were racemic (D/L approximately 1), indicat ing that these amino acids are indigenous to the meteorite and not te rrestrial contaminants. Several other non-protein amino acids were also identified in the meteorite above background levels including alpha -aminoisobutyric acid (alpha-AIB), 4-amino-2- methybutanoic acid, 4-a mino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. Th e total abundances of isovaline and AlB in Almahata Sitta are approximately 1000 times lower than the abundances of these amino acids found in the CM carbonaceous meteorite Murchison. The extremely love abund ances and unusual distribution of five carbon amino acids in Almahata Sitta compared to Cl, CM, and CR carbonaceous meteorites and may be due to extensive thermal alteration of amino acids on the parent aster oid by partial melting during formation or impact shock heating.

  19. Characterization and multilineage differentiation of embryonic stem cells derived from a buffalo parthenogenetic embryo.

    Science.gov (United States)

    Sritanaudomchai, Hathaitip; Pavasuthipaisit, Kanok; Kitiyanant, Yindee; Kupradinun, Piengchai; Mitalipov, Shoukhrat; Kusamran, Thanit

    2007-10-01

    Embryonic stem (ES) cells derived from mammalian embryos have the ability to form any terminally differentiated cell of the body. We herein describe production of parthenogenetic buffalo (Bubalus Bubalis) blastocysts and subsequent isolation of an ES cell line. Established parthenogenetic ES (PGES) cells exhibited diploid karyotype and high telomerase activity. PGES cells showed remarkable long-term proliferative capacity providing the possibility for unlimited expansion in culture. Furthermore, these cells expressed key ES cell-specific markers defined for primate species including stage-specific embryonic antigen-4 (SSEA-4), tumor rejection antigen-1-81 (TRA-1-81), and octamer-binding transcription factor 4 (Oct-4). In vitro, in the absence of a feeder layer, cells readily formed embryoid bodies (EBs). When cultured for an extended period of time, EBs spontaneously differentiated into derivatives of three embryonic germ layers as detected by PCR for ectodermal (nestin, oligodendrocytes, and tubulin), mesodermal (scleraxis, alpha-skeletal actin, collagen II, and osteocalcin) and endodermal markers (insulin and alpha-fetoprotein). Differentiation of PGES cells toward chondrocyte lineage was directed by supplementing serum-containing media with ascorbic acid, beta-glycerophosphate, and dexamethasone. Moreover, when PGES cells were injected into nude mice, teratomas with derivatives representing all three embryonic germ layers were produced. Our results suggest that the cell line isolated from a parthenogenetic blastocyst holds properties of ES cells, and can be used as an in vitro model to study the effects of imprinting on cell differentiation and as an a invaluable material for extensive molecular studies on imprinted genes.

  20. [Use of organic acids in acne and skin discolorations therapy].

    Science.gov (United States)

    Kapuścińska, Alicja; Nowak, Izabela

    2015-03-22

    Acne is one of the most frequent skin disorders that occurs in puberty, but often adults also have acne. The most important factors responsible for acne are elevated production of sebum by hyperactive sebaceous glands and blockage of the follicle because of hyperkeratosis [14]. The third etiopathogenic factor of acne is excessive microflora reproduction [8]. The most significant bacterium that is responsible for formation of skin lesions is Propionibacterium acnes, a rod-shaped Gram-positive and aerotolerant anaerobic bacterium. It is estimated that P. acnes is responsible for acne in approximately 80% of people aged 11 to 30 [27,40]. Even healed skin lesions can often cause skin discolorations and scar formation [51]. Exfoliating chemical substances that are commonly used in dermatology and cosmetology are organic acids. Exfoliating treatment using organic acids is called "chemical peeling" and consists of controlled application of those substances on the skin [38]. The depth of exfoliation depends on organic acid concentration, type of substance and contact time with the skin [41]. Using exfoliating agents seems to be helpful in excessive keratinization - one of several factors responsible for acne. Moreover, epidermis exfoliation is a popular method of removing skin discoloration [22]. Considering chemical structure, exfoliating substances that are most often used in cosmetology contain alpha-hydroxyacids (glycolic acid, lactic acid, mandelic acid and citric acid), beta-hydroxyacids (salicylic acid) and other organic acids, such as trichloroacetic acid and pyruvic acid [47]. In this article, a literature review of use of organic acids in acne and skin discoloration therapy is presented.

  1. Effects of Cysteamine on Sheep Embryo Cleavage Rates

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    Sinem Ö. ENGİNLER

    2015-01-01

    Full Text Available Oxidative stress during in vitro culture leads to defects in development of gametes and embryos. Several antioxidants such as cysteamine, L-ascorbic acid, beta mercaptoethanol, cysteine, glutathione, proteins, vitamins have been used to supplement culture media to counter the oxidative stress. This study was conducted to detect the effect of adding cysteamine to the maturation medium to subsequent cleavage rates of sheep embryos. Totally 604 ovaries were obtained by ten replica and 2060 oocytes were collected. The cumulus oocyte complexes were recovered by the slicing method. A total of 1818 selected oocytes were divided into two groups and used for maturation (88.25%. The first group was created as supplemented with cysteamine (Group A and second group (Group B, control without cysteamine in TCM-199. The two groups were incubated for 24 h at 38.8 °C in an atmosphere of 5% CO2 in humidified air for in vitro maturation (IVM. After IVM, oocytes were fertilized with 50 x 107 / mL fresh ram semen in BSOF medium for 18 h. After fertilization, maturation groups were divided into two subgroups with different culture media: Group AI-SOF (Synthetic Oviduct Fluid medium, Group AII-CR1aa (Charles Rosencrans medium, Group BI-SOF and Group BII-CR1aa were achieved. Cleavage rates were evaluated at day 2. post insemination. The rates of cleavage were detected as 59.54% (184/309, 55.44% (173/312, 65.34% (215/329, 59.34% (200/337 respectively, with showing no statistically significant difference between the groups at the level of P>0.05. In conclusion, supplementing cysteamine to maturation media in TCM-199 did not affect the cleavage rates of sheep embryos in SOF and CR1aa culture media.

  2. Effects of culture conditions on estrogen-mediated hepatic in vitro gene expression and correlation to in vivo responses.

    Science.gov (United States)

    Fong, C J; Burgoon, L D; Zacharewski, T R

    2006-08-15

    Refinement of in vitro systems for predictive toxicology is important in order to develop high-throughput early toxicity screening assays and to minimize animal testing studies. This study assesses the ability of mouse Hepa-1c1c7 hepatoma cell model under differing culture conditions to predict in vivo estrogen-induced hepatic gene expression changes. Custom mouse cDNA microarrays were used to compare Hepa-1c1c7 temporal gene expression profiles treated with 10 nM 17beta-estradiol (E2) in serum-free and charcoal-stripped serum supplemented media at 1, 2, 4, 8, 12, and 24 h. Stripped serum supplemented media increased the number gene expression changes and overall responsiveness likely due to the presence of serum factors supporting proliferation and mitochondrial activity. Data from both experiments were compared to a gene expression time course study examining the hepatic effects of 100 microg/kg 17alpha-ethynyl estradiol (EE) in C57BL/6 mice at 2, 4, 8, 12, 18, and 24 h. Only 18 genes overlapped between the serum-free and in vivo studies, whereas 238 genes were in common between Hepa-1c1c7 cells in stripped serum data and C57BL/6 liver samples. Stripped serum cultured cells exhibited E2-elicited gene expression changes associated with proliferation, cytoskeletal re-organization, cholesterol uptake and synthesis, increased fatty acid beta-oxidation, and oxidative stress, which correlated with in vivo hepatic responses. These results demonstrate that E2 treatment of Hepa-1c1c7 cells in serum supplemented media modulate responses in selected pathways which appropriately model estrogen-elicited in vivo hepatic responses.

  3. Antimicrobial and anti-inflammatory activity of folklore: Mallotus peltatus leaf extract.

    Science.gov (United States)

    Chattopadhyay, Debprasad; Arunachalam, G; Mandal, Asit B; Sur, Tapas K; Mandal, Subash C; Bhattacharya, S K

    2002-10-01

    Since ages Mallotus peltatus (Geist) Muell. Arg. var acuminatus (Euphorbiaceae) leaf and stem bark is used in folk medicine to cure intestinal ailments and skin infections. In several intestinal ailments, localized inflammation is of common occurrence and hence we have evaluated the antimicrobial as well as anti-inflammatory activity of M. peltatus leaf extract. The crude methanol extract of M. peltatus leaves was found to be active against Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus faecalis, Bacillus subtilis, Escherichia coli and Proteus mirabilis and the dermatophytic fungi Microsporum gypseum. The minimum inhibitory concentration (MIC) ranges from 128 to 2000 microg ml(-1) for bacteria and 128 mg ml(-1) for fungi, while the minimum bactericidal concentration (MBC) was 2-4-fold higher than MIC. The methanol-water fraction of the extract showed similar activity against Staphylococcus, Streptococcus, Bacillus and Proteus isolates. The anti-inflammatory activity of the extract against carrageenan (acute model) and dextran-induced (subacute model) rat paw oedema and cotton pellet-induced granuloma (chronic model) in rats were studied using indomethacin (10 mg kg(-1)), a nonsteroid anti-inflammatory drug, as standard. The methanol extract at 200 and 400 mg kg(-1), and the n-butanol fractions A and B at 25 mg kg(-1), exhibited significant anti-inflammatory activity in Albino rats, compared with indomethacin. Phytochemical study revealed the presence of tannins, saponins, terpenoids, steroids and reducing sugars in the crude extract while the n-butanol fractions showed the presence of ursolic acid, beta-sitosterol and some fatty acids as major compounds. Further study with fractions showed that the antibacterial and anti-inflammatory activity is due to either fraction A (ursolic acid) alone or the combination of fractions A and B (beta-sitosterol and fatty acids) of the extract.

  4. In vitro susceptibility to antimicrobial agents and ultrastructural characteristics related to swimming motility and drug action in Campylobacter jejuni and C. coli.

    Science.gov (United States)

    Yabe, Shizuka; Higuchi, Wataru; Takano, Tomomi; Razvina, Olga; Iwao, Yasuhisa; Isobe, Hirokazu; Yamamoto, Tatsuo

    2010-06-01

    Campylobacter jejuni has recently been noted as the most common cause of bacterial food-borne diseases in Japan. In this study, we examined in vitro susceptibility to 36 antimicrobial agents of 109 strains of C. jejuni and C. coli isolated from chickens and patients with enteritis or Guillain-Barré syndrome from 1996 to 2009. Among these agents, carbapenems (imipenem, meropenem, panipenem, and biapenem) showed the greatest activity [minimal inhibitory concentration (MIC)(90), 0.03-0.125 microg/ml]. This was followed by sitafloxacin (MIC(90), 0.25 microg/ml), furazolidone and azithromycin (MIC(90), 0.5 microg/ml), gentamicin and clindamycin (MIC(90), 1 microg/ml), and clavulanic acid (beta-lactamase inhibitor; MIC(90), 2 microg/ml). All or most strains were resistant to aztreonam, sulfamethoxazole, and trimethoprim. Marked resistance was also observed for levofloxacin and tetracyclines. Resistance was not present for macrolides and rare for clindamycin. C. jejuni (and C. coli) exhibited high swimming motility and possessed a unique end-side (cup-like) structure at both ends, in contrast to Helicobacter pylori and Vibrio cholerae O1 and O139. The morphology of C. jejuni (and C. coli) changed drastically after exposure to imipenem (coccoid formation), meropenem (bulking and slight elongation), and sitafloxacin (marked elongation), and exhibited reduced motility. In the HEp-2 cell adherence model, unusually elongated bacteria were also observed for sitafloxacin. The data suggest that although resistance to antimicrobial agents (e.g., levofloxacin) has continuously been noted, carbapenems, sitafloxacin, and others such as beta-lactamase inhibitors alone showed good in vitro activity and that C. jejuni (and C. coli) demonstrated a unique ultrastructural nature related to high swimming motility and drug action.

  5. Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

    Science.gov (United States)

    Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.

    2010-01-01

    Amino acid analysis of a meteorite fragment of asteroid 2008 TC3 called Almahata Sitta was carried out using reverse-phase liquid chromatography coupled with UV fluorescence detection and time-of-flight mass spectrometry (LC-FD/ToF-MS) as part of a sample analysis consortium. LC-FD/ToF-MS analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to seven-carbon aliphatic amino acids and one- to three-carbon amines with abundances ranging from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, R-amino-n-butyric acid (beta-ABA), 2-amino-2-methylbutanoic acid (isovaline), and 2-aminopentanoic acid (norvaline) in the meteorite were racemic (D/L approximately 1), indicating that these amino acids are indigenous to the meteorite and not terrestrial contaminants. Several other non-protein amino acids were also identified in the meteorite above background levels including alpha-aminoisobutyric acid (alpha-AIB), 4-amino-2- methylbutanoic acid, 4-amino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. The total abundances of isovaline and alpha-AIB in Almahata Sitta are 1000 times lower than the abundances of these amino acids found in the CM carbonaceous chondrite Murchison. The extremely low abundances and unusual distribution of five carbon amino acids in Almahata Sitta compared to Cl, CM, and CR carbonaceous chondrites may reflect extensive thermal alteration of amino acids on the parent asteroid by partial melting during formation or subsequent impact shock heating. It is also possible that amino acids were synthesized by catalytic reactions on the parent body after asteroid 2008 TC3 cooled to lower temperatures.

  6. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Zaya, Renee M., E-mail: renee.zaya@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Amini, Zakariya, E-mail: zakariya.amini@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Whitaker, Ashley S., E-mail: ashley.s.whitaker@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Ide, Charles F., E-mail: charles.ide@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States)

    2011-08-15

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 {mu}g/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 {mu}g/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 {mu}g/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 {mu}g/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor {beta} (PPAR-{beta}) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid {beta}-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-{beta}, an energy

  7. X-linked adrenoleukodystrophy in women: a cross-sectional cohort study.

    Science.gov (United States)

    Engelen, Marc; Barbier, Mathieu; Dijkstra, Inge M E; Schür, Remmelt; de Bie, Rob M A; Verhamme, Camiel; Dijkgraaf, Marcel G W; Aubourg, Patrick A; Wanders, Ronald J A; van Geel, Bjorn M; de Visser, Marianne; Poll-The, Bwee T; Kemp, Stephan

    2014-03-01

    X-linked adrenoleukodystrophy is the most common peroxisomal disorder. The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal transporter of very long-chain fatty acids. A defect in the ABCD1 protein results in elevated levels of very long-chain fatty acids in plasma and tissues. The clinical spectrum in males with X-linked adrenoleukodystrophy has been well described and ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. As in many X-linked diseases, it was assumed that female carriers remain asymptomatic and only a few studies addressed the phenotype of X-linked adrenoleukodystrophy carriers. These studies, however, provided no information on the prevalence of neurological symptoms in the entire population of X-linked adrenoleukodystrophy carriers, since data were acquired in small groups and may be biased towards women with symptoms. Our primary goal was to investigate the symptoms and their frequency in X-linked adrenoleukodystrophy carriers. The secondary goal was to determine if the X-inactivation pattern of the ABCD1 gene was associated with symptomatic status. We included 46 X-linked adrenoleukodystrophy carriers in a prospective cross-sectional cohort study. Our data show that X-linked adrenoleukodystrophy carriers develop signs and symptoms of myelopathy (29/46, 63%) and/or peripheral neuropathy (26/46, 57%). Especially striking was the occurrence of faecal incontinence (13/46, 28%). The frequency of symptomatic women increased sharply with age (from 18% in women 60 years of age). Virtually all (44/45, 98%) X-linked adrenoleukodystrophy carriers had increased very long-chain fatty acids in plasma and/or fibroblasts, and/or decreased very long-chain fatty acids beta-oxidation in fibroblasts. We did not find an association between the X-inactivation pattern and symptomatic status. We conclude that X-linked adrenoleukodystrophy carriers develop an

  8. Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation

    Directory of Open Access Journals (Sweden)

    Mathavan Sinnakaruppan

    2010-03-01

    Full Text Available Abstract Background Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies. Results Hepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations. Conclusion Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling

  9. AMPK activation represses the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase: Role of nuclear respiratory factor-1

    Energy Technology Data Exchange (ETDEWEB)

    Adam, Tasneem; Opie, Lionel H. [Hatter Cardiovascular Research Institute, Faculty of Health Sciences, University of Cape Town, Observatory 7925 (South Africa); Essop, M. Faadiel, E-mail: mfessop@sun.ac.za [Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7600 (South Africa)

    2010-07-30

    Research highlights: {yields} AMPK inhibits acetyl-CoA carboxylase beta gene promoter activity. {yields} Nuclear respiratory factor-1 inhibits acetyl-CoA carboxylase beta promoter activity. {yields} AMPK regulates acetyl-CoA carboxylase beta at transcriptional level. -- Abstract: The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC{beta}) produces malonyl-CoA, a potent inhibitor of carnitine palmitoyltransferase-1. AMPK inhibits ACC{beta} activity, lowering malonyl-CoA levels and promoting mitochondrial fatty acid {beta}-oxidation. Previously, AMPK increased promoter binding of nuclear respiratory factor-1 (NRF-1), a pivotal transcriptional modulator controlling gene expression of mitochondrial proteins. We therefore hypothesized that NRF-1 inhibits myocardial ACC{beta} promoter activity via AMPK activation. A human ACC{beta} promoter-luciferase construct was transiently transfected into neonatal cardiomyocytes {+-} a NRF-1 expression construct. NRF-1 overexpression decreased ACC{beta} gene promoter activity by 71 {+-} 4.6% (p < 0.001 vs. control). Transfections with 5'-end serial promoter deletions revealed that NRF-1-mediated repression of ACC{beta} was abolished with a pPII{beta}-18/+65-Luc deletion construct. AMPK activation dose-dependently reduced ACC{beta} promoter activity, while NRF-1 addition did not further decrease it. We also investigated NRF-1 inhibition in the presence of upstream stimulatory factor 1 (USF1), a known transactivator of the human ACC{beta} gene promoter. Here NRF-1 blunted USF1-dependent induction of ACC{beta} promoter activity by 58 {+-} 7.5% (p < 0.001 vs. control), reversed with a dominant negative NRF-1 construct. NRF-1 also suppressed endogenous USF1 transcriptional activity by 55 {+-} 6.2% (p < 0.001 vs. control). This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACC{beta} gene promoter in the mammalian heart. Our data extends AMPK regulation of ACC{beta} to the transcriptional level.

  10. Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4 defines a new subtype of D-bifunctional protein deficiency

    Directory of Open Access Journals (Sweden)

    McMillan Hugh J

    2012-11-01

    Full Text Available Abstract Background D-bifunctional protein (DBP deficiency is typically apparent within the first month of life with most infants demonstrating hypotonia, psychomotor delay and seizures. Few children survive beyond two years of age. Among patients with prolonged survival all demonstrate severe gross motor delay, absent language development, and severe hearing and visual impairment. DBP contains three catalytically active domains; an N-terminal dehydrogenase, a central hydratase and a C-terminal sterol carrier protein-2-like domain. Three subtypes of the disease are identified based upon the domain affected; DBP type I results from a combined deficiency of dehydrogenase and hydratase activity; DBP type II from isolated hydratase deficiency and DBP type III from isolated dehydrogenase deficiency. Here we report two brothers (16½ and 14 years old with DBP deficiency characterized by normal early childhood followed by sensorineural hearing loss, progressive cerebellar and sensory ataxia and subclinical retinitis pigmentosa. Methods and results Biochemical analysis revealed normal levels of plasma VLCFA, phytanic acid and pristanic acid, and normal bile acids in urine; based on these results no diagnosis was made. Exome analysis was performed using the Agilent SureSelect 50Mb All Exon Kit and the Illumina HiSeq 2000 next-generation-sequencing (NGS platform. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within the dehydrogenase domain (c.101C>T; p.Ala34Val and hydratase domain (c.1547T>C; p.Ile516Thr of the 17β-hydroxysteroid dehydrogenase type 4 gene (HSD17B4. These mutations have been previously reported in patients with severe-forms of DBP deficiency, however each mutation was reported in combination with another mutation affecting the same domain. Subsequent studies in fibroblasts revealed normal VLCFA levels, normal C26:0 but reduced pristanic acid beta-oxidation activity. Both DBP

  11. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yang [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100080 (China); Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Dai Jiayin [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China)], E-mail: daijy@ioz.ac.cn

    2008-09-29

    (ATPo6). These results demonstrate that turbulence of fatty acid {beta}-oxidation and oxidative stress responses were involved in the PFDoA-induced hepatotoxicity.

  12. Proteomic analysis of pathogenesis-related proteins (PRs) induced by compatible and incompatible interactions of pepper mild mottle virus (PMMoV) in Capsicum chinense L3 plants.

    Science.gov (United States)

    Elvira, Maria Isabel; Galdeano, Myriam Molina; Gilardi, Patricia; García-Luque, Isabel; Serra, Maria Teresa

    2008-01-01

    Resistance conferred by the L(3) gene is active against most of the tobamoviruses, including the Spanish strain (PMMoV-S), a P(1,2) pathotype, but not against certain strains of pepper mild mottle virus (PMMoV), termed P(1,2,3) pathotype, such as the Italian strain (PMMoV-I). Both viruses are nearly identical at their nucleotide sequence level (98%) and were used to challenge Capsicum chinense PI159236 plants harbouring the L(3) gene in order to carry out a comparative proteomic analysis of PR proteins induced in this host in response to infection by either PMMoV-S or PMMoV-I. PMMoV-S induces a hypersensitive reaction (HR) in C. chinense PI159236 plant leaves with the formation of necrotic local lesions and restriction of the virus at the primary infection sites. In this paper, C. chinense PR protein isoforms belonging to the PR-1, beta-1,3-glucanases (PR-2), chitinases (PR-3), osmotin-like protein (PR-5), peroxidases (PR-9), germin-like protein (PR-16), and PRp27 (PR-17) have been identified. Three of these PR protein isoforms were specifically induced during PMMoV-S-activation of C. chinense L(3) gene-mediated resistance: an acidic beta-1,3-glucanase isoform (PR-2) (M(r) 44.6; pI 5.1), an osmotin-like protein (PR-5) (M(r) 26.8; pI 7.5), and a basic PR-1 protein isoform (M(r) 18; pI 9.4-10.0). In addition, evidence is presented for a differential accumulation of C. chinense PR proteins and mRNAs in the compatible (PMMoV-I)-C. chinense and incompatible (PMMoV-S)-C. chinense interactions for proteins belonging to all PR proteins detected. Except for an acidic chitinase (PR-3) (M(r) 30.2; pI 5.0), an earlier and higher accumulation of PR proteins and mRNAs was detected in plants associated with HR induction. Furthermore, the accumulation rates of PR proteins and mRNA did not correlate with maximal accumulation levels of viral RNA, thus indicating that PR protein expression may reflect the physiological status of the plant.

  13. Effects of pH and Iminosugar Pharmacological Chaperones on Lysosomal Glycosidase Structure and Stability

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    Lieberman, Raquel L.; D’aquino, J. Alejandro; Ringe, Dagmar; Petsko, Gregory A.; (Harvard-Med); (Brandeis)

    2009-06-05

    Human lysosomal enzymes acid-{beta}-glucosidase (GCase) and acid-{alpha}-galactosidase ({alpha}-Gal A) hydrolyze the sphingolipids glucosyl- and globotriaosylceramide, respectively, and mutations in these enzymes lead to the lipid metabolism disorders Gaucher and Fabry disease, respectively. We have investigated the structure and stability of GCase and {alpha}-Gal A in a neutral-pH environment reflective of the endoplasmic reticulum and an acidic-pH environment reflective of the lysosome. These details are important for the development of pharmacological chaperone therapy for Gaucher and Fabry disease, in which small molecules bind mutant enzymes in the ER to enable the mutant enzyme to meet quality control requirements for lysosomal trafficking. We report crystal structures of apo GCase at pH 4.5, at pH 5.5, and in complex with the pharmacological chaperone isofagomine (IFG) at pH 7.5. We also present thermostability analysis of GCase at pH 7.4 and 5.2 using differential scanning calorimetry. We compare our results with analogous experiments using {alpha}-Gal A and the chaperone 1-deoxygalactonijirimycin (DGJ), including the first structure of {alpha}-Gal A with DGJ. Both GCase and {alpha}-Gal A are more stable at lysosomal pH with and without their respective iminosugars bound, and notably, the stability of the GCase-IFG complex is pH sensitive. We show that the conformations of the active site loops in GCase are sensitive to ligand binding but not pH, whereas analogous galactose- or DGJ-dependent conformational changes in {alpha}-Gal A are not seen. Thermodynamic parameters obtained from {alpha}-Gal A unfolding indicate two-state, van't Hoff unfolding in the absence of the iminosugar at neutral and lysosomal pH, and non-two-state unfolding in the presence of DGJ. Taken together, these results provide insight into how GCase and {alpha}-Gal A are thermodynamically stabilized by iminosugars and suggest strategies for the development of new pharmacological

  14. Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH in rats

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    Giannini Augusto

    2010-05-01

    Full Text Available Abstract Background Azoxymethane (AOM or 1,2-dimethylhydrazine (DMH-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. Methods For gene expression analysis, 9 tumours (TUM and their paired normal mucosa (NM were hybridized on 4 × 44K Whole rat arrays (Agilent and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent and the results were analyzed by CGH Analytics (Agilent. Results Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC compared with NM: 183, 48, 39, 38, 36 and 32, respectively, while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively. Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 including Apc. Conclusion The results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a

  15. Effect of acetate formation pathway and long chain fatty acid CoA-ligase on the free fatty acid production in E. coli expressing acy-ACP thioesterase from Ricinus communis.

    Science.gov (United States)

    Li, Mai; Zhang, Xiujun; Agrawal, Arpita; San, Ka-Yiu

    2012-07-01

    Microbial biosynthesis of fatty acid like chemicals from renewable carbon sources has attracted significant attention in recent years. Free fatty acids can be used as precursors for the production of fuels or chemicals. Wild type E. coli strains produce fatty acids mainly for the biosynthesis of lipids and cell membranes and do not accumulate free fatty acids as intermediates in lipid biosynthesis. However, free fatty acids can be produced by breaking the fatty acid elongation through the overexpression of an acyl-ACP thioesterase. Since acetyl-CoA might be an important factor for fatty acid synthesis (acetate formation pathways are the main competitive pathways in consuming acetyl-CoA or pyruvate, a precursor of acetyl-CoA), and the long chain fatty acid CoA-ligase (FadD) plays a pivotal role in the transport and activation of exogenous fatty acids prior to their subsequent degradation, we examined the composition and the secretion of the free fatty acids in four different strains including the wild type MG1655, a mutant strain with inactivation of the fatty acid beta-oxidation pathway (fadD mutant (ML103)), and mutant strains with inactivation of the two major acetate production pathways (an ack-pta (acetate kinase/phosphotransacetylase), poxB (pyruvate oxidase) double mutant (ML112)) and a fadD, ack-pta, poxB triple mutant (ML115). The engineered E. coli cells expressing acyl-ACP thioesterase with glucose yield is higher than 40% of theoretical yield. Compared to MG1655(pXZ18) and ML103(pXZ18), acetate forming pathway deletion strains such as ML112(pXZ18) and ML115(pXZ18) produced similar quantity of total free fatty acids, which indicated that acetyl-CoA availability does not appear to be limiting factor for fatty acid production in these strains. However, these strains did show significant differences in the composition of free fatty acids. Different from MG1655(pXZ18) and ML103(pXZ18), acetate formation pathway deletion strains such as ML112(pXZ18) and ML115

  16. NR4A nuclear receptors mediate carnitine palmitoyltransferase 1A gene expression by the rexinoid HX600

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    Ishizawa, Michiyasu [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan); Kagechika, Hiroyuki [Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Makishima, Makoto, E-mail: makishima.makoto@nihon-u.ac.jp [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer The function of RXR heterodimers with NR4 receptors remains unknown. Black-Right-Pointing-Pointer The RXR ligand HX600 induces expression of carnitine palmitoyltransferase 1A (CPT1A). Black-Right-Pointing-Pointer HX600-induced CPT1A expression is mediated by the NR4 receptors, Nur77 and NURR1. Black-Right-Pointing-Pointer CPT1A induction by HX600 is not mediated by de novo protein synthesis. Black-Right-Pointing-Pointer CPT1A could be a target of the Nur77-RXR and NURR1-RXR heterodimers. -- Abstract: Retinoid X receptors (RXRs) are members of the nuclear receptor superfamily and can be activated by 9-cis retinoic acid (9CRA). RXRs form homodimers and heterodimers with other nuclear receptors such as the retinoic acid receptor and NR4 subfamily nuclear receptors, Nur77 and NURR1. Potential physiological roles of the Nur77-RXR and NURR1-RXR heterodimers have not been elucidated. In this study, we identified a gene regulated by these heterodimers utilizing HX600, a selective RXR agonist for Nur77-RXR and NURR1-RXR. While 9CRA induced many genes, including RAR-target genes, HX600 effectively induced only carnitine palmitoyltransferase 1A (CPT1A) in human teratocarcinoma NT2/D1 cells, which express RXR{alpha}, Nur77 and NURR1. HX600 also increased CPT1A expression in human embryonic kidney (HEK) 293 cells and hepatocyte-derived HepG2 cells. Although HX600 induced CPT1A less effectively than 9CRA, overexpression of Nur77 or NURR1 increased the HX600 response to levels similar to 9CRA in NT2/D1 and HEK293 cells. A dominant-negative form of Nur77 or NURR1 repressed the induction of CPT1A by HX600. A protein synthesis inhibitor did not alter HX600-dependent CPT1A induction. Thus, the rexinoid HX600 directly induces expression of CPT1A through a Nur77 or NURR1-mediated mechanism. CPT1A, a gene involved in fatty acid {beta}-oxidation, could be a target of RXR-NR4 receptor heterodimers.

  17. Glutamic acid gamma-monohydroxamate and hydroxylamine are alternate substrates for Escherichia coli asparagine synthetase B.

    Science.gov (United States)

    Boehlein, S K; Schuster, S M; Richards, N G

    1996-03-01

    Escherichia coli asparagine synthetase B (AS-B) catalyzes the synthesis of asparagine from aspartic acid and glutamine in an ATP-dependent reaction. The ability of this enzyme to employ hydroxylamine and L-glutamic acid gamma-monohydroxamate (LGH) as alternative substrates in place of ammonia and L-glutamine, respectively, has been investigated. The enzyme is able to function as an amidohydrolase, liberating hydroxylamine from LGH with high catalytic efficiency, as measured by k(cat)/K(M). In addition, the kinetic parameters determined for hydroxylamine in AS-B synthetase activity are very similar to those of ammonia. Nitrogen transfer from LGH to yield aspartic acid beta-monohydroxamate is also catalyzed by AS-B. While such an observation has been made for a few members of the trpG amidotransferase family, our results appear to be the first demonstration that nitrogen transfer can occur from glutamine analogs in a purF amidotransferase. However, k(cat)/K(M) for the ATP-dependent transfer of hydroxylamine from LGH to aspartic acid is reduced 3-fold relative to that for glutamine-dependent asparagine synthesis. Further, the AS-B mutant in which asparagine is replaced by alanine (N74A) can also use hydroxylamine as an alternate substrate to ammonia and catalyze the hydrolysis of LGH. The catalytic efficiencies (k(cat)/K(M)) of nitrogen transfer from LGH and L-glutamine to beta-aspartyl-AMP are almost identical for the N74A AS-B mutant. These observations support the proposal that Asn-74 plays a role in catalyzing glutamine-dependent nitrogen transfer. We interpret our kinetic data as further evidence against ammonia-mediated nitrogen transfer from glutamine in the purF amidotransferase AS-B. These results are consistent with two alternate chemical mechanisms that have been proposed for this reaction [Boehlein, S. K., Richards, N. G. J., Walworth, E. S., & Schuster, S. M. (1994) J. Biol. Chem. 269, 26789-26795].

  18. CYP1B1基因敲除对成年小鼠肝脏脂肪代谢的影响及可能机制%ROLE OF CYP1B1 IN HEPATIC LIPID METABOLISM OF ADULT MICE AND ITS POSSIBLE MECHANISM

    Institute of Scientific and Technical Information of China (English)

    刘小聪; 赵丽华; 冯婧; Colin RJ; 王素青

    2012-01-01

    CYP1B1 deletion suppressed a set of genes expression which was involved in fatty acid synthesis such as CD36< SCD1 and SREBPlc, and enhanced CPTla, UCP-2 expressions, which were involved in fatty acid beta oxidation. Conclusion CYP1B1 deletion may prevent adult mice from HFD-induced obesity through adenosine monophosphate kinase (AMPK) activation, which regulates downstream hepatic lipid metabolic genes expression.

  19. Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study

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    Almotasembellah Aljaafareh

    2016-09-01

    Full Text Available Objectives: Long-acting bronchodilators are mainstay treatment for moderate to severe chronic obstructive pulmonary disease. A growing body of evidence indicates an increased risk of cardiovascular events upon initiation of these medications. We hypothesize that this risk is higher in patients with chronic obstructive pulmonary disease who had a preexisting cardiovascular disease regardless of receipt of any cardiovascular medication. Methods: A retrospective cohort of patients with a diagnosis of chronic obstructive pulmonary disease based on two outpatient visits or one inpatient visit for chronic obstructive pulmonary disease (International Classification of Diseases, 9th Edition, Clinical Modification codes 491.x, 492.x, 496 in any year between 2001 and 2012 from a commercial insurance database. We then selected those initiating long-acting bronchodilator treatments between April 2001 and September 2012. Each patient had a 1 year look back period to determine history of cardiovascular disease or cardiovascular disease treatment from the time of first prescription of long-acting beta agonist, long-acting muscarinic antagonist, or long-acting beta agonist combined with inhaled corticosteroids. Patients were followed for 90 days for hospitalizations or emergency department visits for cardiovascular event. The cohort was divided into four groups based on the presence of cardiovascular disease (including ischemic heart disease, hypertension, ischemic stroke, heart failure, tachyarrhythmias and artery disease based on International Classification of Diseases, 9th Edition, Clinical Modification codes and cardiovascular disease treatment defined as acetylsalicylic acid, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet, anticoagulants, calcium channel blockers, nitrate, digoxin, diuretics, antiarrhythmics or statins. Odds of emergency department visit or hospitalization in the 90 days after

  20. n-3 LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1

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    Tapia, G. S.

    2016-06-01

    Full Text Available The aim of this study was to investigate the roles of the Acyl co-enzyme A oxidase (ACOX, carnitine acyl transferase I (CAT-1 and activating protein 1 (AP-1 in the reversal of hepatic steatosis with dietary change and n-3 long chain polyunsaturated fatty acid (n-3 LCPUFA supplementation. Male C57BL/6J mice were given either a control diet (CD or a high fat diet (HFD for 12 weeks, and then continued with the CD or CD plus n-3 LCPUFA for eight weeks. After this period, body and adipose visceral tissue weight were analyzed and liver samples were taken to measure ACOX, CAT-1 and c-jun levels. The dietary change from HFD to a norm caloric diet plus n-3 LCPUFA supplementation significantly reduced liver steatosis and adipose tissue: body weight ratio, along with an increase in the hepatic ACOX and CAT-1 levels and normalization of AP-1 expression that could favor the fatty acid beta-oxidation over lipogenesis and regulate inflammation. These results provide new data on the enzymatic metabolism underlying dietary change to a norm caloric diet plus n-3 LCPUFA supplementation.El objetivo de este estudio fue investigar el rol de las enzimas Acil coenzima A oxidasa (ACOX y Acil carnitina transferasa 1 (CAT-1, además del factor de transcripción, Proteína activadora 1 (AP-1 en la reversión de la esteatosis hepática mediante cambio de dieta más suplementación con Ácidos grasos poliinsaturados de cadena larga omega tres (AGPICL n-3. Ratones macho de la cepa C57BL/6J fueron alimentados con dieta control (DC o alta en grasas (DAG durante 12 semanas, luego continuaron con DC con o sin suplementación de AGPICL n-3 durante 8 semanas. Después de este período, se analizó el peso corporal y del tejido adiposo visceral; en las muestras hepáticas se evaluaron los niveles de ACOX, CAT-1 y AP-1. El cambio a dieta control más suplementación con AGPICL n-3 reduce significativamente la esteatosis hepática y la relación tejido adiposo/peso corporal, acompa

  1. Uso de suplementos alimentares por adolescentes Dietary supplement use by adolescents

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    Crésio Alves

    2009-08-01

    : Consumption of dietary supplements is widely spread among adolescents. This habit has often been detected in pediatric and adolescent medicine clinics. Most of the time, the use of supplements is motivated by the search of the "ideal body." Other reasons for this practice are: attempt to compensate for an inadequate diet, increase immunity, prevent diseases, improve athletic performance and overcome their own athletic limits. The dietary supplements most frequently used and for which there is little evidence of beneficial effects in healthy adolescents are: proteins, amino acids, beta-hydroxy-beta-methylbutyrate, microelements, carnitine, creatine, vitamins, caffeine, and bicarbonate. This dietary supplementation may be beneficial for competitive athletes who do not have a balanced diet after a specific dietary deficiency has been detected. CONCLUSION: The unrestrained consumption of dietary supplements should be avoided, since, besides the lack of evidence that such practice will lead to improvement of performance, it exposes adolescents to several adverse effects. Balanced nutrition, with intake of essential energy and nutrients is usually enough to achieve good athletic performance. The use of dietary supplements must be allowed only for selected cases in which specific nutritional deficiencies are identified.

  2. Suitability analysis of fresh-cut vegetable processing for twenty main green capsicum cultivars in China%中国主栽青辣椒品种鲜切加工适宜性评价

    Institute of Scientific and Technical Information of China (English)

    沈月; 高美须; 杨丽; 赵鑫; 陈雪; 王志东; 李淑荣; 王丽

    2016-01-01

    correlation coefficient was 0.72. Sugar-acid ratio and titratable acid showed significantly negative correlation and the correlation coefficient was -0.81. Vitamin C content showed positive correlation with FRAP value, ABTS value and total phenol content, and the correlation coefficient was 0.69, 0.73 and 0.58 respectively. Pulp thickness had negative correlation with vitamin C content and total phenol content, and the correlation coefficient was -0.5 and -0.6 respectively. Beta carotene content had significantly negative correlation withL*andb*value and the correlation coefficient was -0.63 and -0.66 respectively. The number of main evaluation indices was determined by principal component analysis, the tested indices at the same level of clustering were divided by variable cluster analysis, and the representative index in each category was decided by factor assessment method; then the 6 indices, including sensory evaluation score, vitamin C content, product yield ratio, ratio of sugar to acid, beta carotene content and total phenol content, were filtered as the main evaluation factors for fresh-cut processing and their weighting was 38.15%, 26.55%, 18.37%, 9.00%, 5.00%, 2.94% respectively, which was determined by APH method. The grey correlation analysis was applied based on above results, and it was found that the best cultivars for fresh-cut processing were “Guofu No. 311” and “Zhongjiao No. 106” for mild spicy green capsicum, “Longjiao No. 6” for spicy green capsicum and “Xingshuzhoupila” for very spicy green capsicum. It is concluded that the collected basic data and the established analysis system can be used for suitability evaluation of fresh-cut vegetable processing, and also provide scientific guidance for green capsicum breeding and breeding of varieties that are rich in functional components.%为科学评价青辣椒品种的鲜切加工适宜性,收集中国主栽青辣椒品种20个,统一种植,在同一成熟度下采收,并对其感