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Sample records for acid-binding protein genes

  1. Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

    Science.gov (United States)

    Gao, G L; Na, W; Wang, Y X; Zhang, H F; Li, H; Wang, Q G

    2015-01-01

    This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes.

  2. Hepatic phenotype of liver fatty acid binding protein gene-ablated mice

    OpenAIRE

    Martin, Gregory G.; Atshaves, Barbara P.; Huang, Huan; McIntosh, Avery L.; Williams, Brad J.; Pai, Pei-Jing; Russell, David H.; Kier, Ann B.; Schroeder, Friedhelm

    2009-01-01

    Although the function of liver fatty acid binding protein in hepatic fatty acid metabolism has been extensively studied, its potential role in hepatic cholesterol homeostasis is less clear. Although hepatic cholesterol accumulation was initially reported in L-FABP-null female mice, that study was performed with early N2 backcross generation mice. To resolve whether the hepatic cholesterol phenotype in these L-FABP−/− mice was attributable to genetic inhomogeneity, these L-FABP−/− mice were fu...

  3. Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58 Linking Lipolysis with Lipid Ligand Shuttling.

    Science.gov (United States)

    Hofer, Peter; Boeszoermenyi, Andras; Jaeger, Doris; Feiler, Ursula; Arthanari, Haribabu; Mayer, Nicole; Zehender, Fabian; Rechberger, Gerald; Oberer, Monika; Zimmermann, Robert; Lass, Achim; Haemmerle, Guenter; Breinbauer, Rolf; Zechner, Rudolf; Preiss-Landl, Karina

    2015-07-24

    The coordinated breakdown of intracellular triglyceride (TG) stores requires the exquisitely regulated interaction of lipolytic enzymes with regulatory, accessory, and scaffolding proteins. Together they form a dynamic multiprotein network designated as the "lipolysome." Adipose triglyceride lipase (Atgl) catalyzes the initiating step of TG hydrolysis and requires comparative gene identification-58 (Cgi-58) as a potent activator of enzyme activity. Here, we identify adipocyte-type fatty acid-binding protein (A-Fabp) and other members of the fatty acid-binding protein (Fabp) family as interaction partners of Cgi-58. Co-immunoprecipitation, microscale thermophoresis, and solid phase assays proved direct protein/protein interaction between A-Fabp and Cgi-58. Using nuclear magnetic resonance titration experiments and site-directed mutagenesis, we located a potential contact region on A-Fabp. In functional terms, A-Fabp stimulates Atgl-catalyzed TG hydrolysis in a Cgi-58-dependent manner. Additionally, transcriptional transactivation assays with a luciferase reporter system revealed that Fabps enhance the ability of Atgl/Cgi-58-mediated lipolysis to induce the activity of peroxisome proliferator-activated receptors. Our studies identify Fabps as crucial structural and functional components of the lipolysome.

  4. Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription.

    Science.gov (United States)

    Schroeder, Friedhelm; Petrescu, Anca D; Huang, Huan; Atshaves, Barbara P; McIntosh, Avery L; Martin, Gregory G; Hostetler, Heather A; Vespa, Aude; Landrock, Danilo; Landrock, Kerstin K; Payne, H Ross; Kier, Ann B

    2008-01-01

    Abnormal energy regulation may significantly contribute to the pathogenesis of obesity, diabetes mellitus, cardiovascular disease, and cancer. For rapid control of energy homeostasis, allosteric and posttranslational events activate or alter activity of key metabolic enzymes. For longer impact, transcriptional regulation is more effective, especially in response to nutrients such as long chain fatty acids (LCFA). Recent advances provide insights into how poorly water-soluble lipid nutrients [LCFA; retinoic acid (RA)] and their metabolites (long chain fatty acyl Coenzyme A, LCFA-CoA) reach nuclei, bind their cognate ligand-activated receptors, and regulate transcription for signaling lipid and glucose catabolism or storage: (i) while serum and cytoplasmic LCFA levels are in the 200 mircroM-mM range, real-time imaging recently revealed that LCFA and LCFA-CoA are also located within nuclei (nM range); (ii) sensitive fluorescence binding assays show that LCFA-activated nuclear receptors [peroxisome proliferator-activated receptor-alpha (PPARalpha) and hepatocyte nuclear factor 4alpha (HNF4alpha)] exhibit high affinity (low nM KdS) for LCFA (PPARalpha) and/or LCFA-CoA (PPARalpha, HNF4alpha)-in the same range as nuclear levels of these ligands; (iii) live and fixed cell immunolabeling and imaging revealed that some cytoplasmic lipid binding proteins [liver fatty acid binding protein (L-FABP), acyl CoA binding protein (ACBP), cellular retinoic acid binding protein-2 (CRABP-2)] enter nuclei, bind nuclear receptors (PPARalpha, HNF4alpha, CRABP-2), and activate transcription of genes in fatty acid and glucose metabolism; and (iv) studies with gene ablated mice provided physiological relevance of LCFA and LCFA-CoA binding proteins in nuclear signaling. This led to the hypothesis that cytoplasmic lipid binding proteins transfer and channel lipidic ligands into nuclei for initiating nuclear receptor transcriptional activity to provide new lipid nutrient signaling pathways that

  5. Localization of the cellular retinoic acid binding protein (CRABP) gene relative to the acute promyelocytic leukemia-associated breakpoint on human chromosome 15

    NARCIS (Netherlands)

    A.H.M. Geurts van Kessel (Ad); H. de Leeuw (H.); E.J. Dekker (E.); J.M. Rijks (Jolianne); N. Spurr (N.); A.M. Ledbetter (Andrew M.); E. Kootwijk (E.); M.J. Vaessen (Marie-Josée)

    1991-01-01

    textabstractA human genomic fragment comprising the cellular retinoic acid binding protein (CRABP) gene was isolated. By using a panel of somatic cell hybrids, this gene could be assigned to human chromosome 15. Subsequently, a possible involvement of the CRABP gene in translocation (15;17) (q22;q11

  6. Association of polymorphisms in adipocyte fatty acid binding protein gene with fat-related traits in chicken

    Institute of Scientific and Technical Information of China (English)

    Manhong YE; Jie WEN; Honghe CAO; Hongbin LI; Jilan CHEN; Guiping ZHAO; Maiqing ZHENG

    2008-01-01

    PCR-SSCP analysis was used to detect poly-morphic sites in chicken adipocyte fatty acid binding pro-tein (A-FABP) gene. Six Chinese local breeds, Beijing-You chicken, Dwarf chicken, Taihe silky chicken, Chong-renma chicken, Xiayan chicken, Luyuan chicken and an introduced foreign breed, Arbor Acre broiler, were used as test populations. Three PCR-SSCP loci were detected. Statistical results showed that frequencies of genotypes and alleles were significantly different in the test popula-tions. Sequence analysis revealed that C → T, G → A, and C → T transitions were responsible for the polymorph-isms. Some fat-related traits such as body weight, content of intramuscular fat (IMF) and percentage of abdominal fat (AFP) were measured in Dwarf chickens and male Beijing-You chickens. We found out that chicken quality was significantly related to different genotypes in these two populations.

  7. Cloning and characterization of the fatty acid-binding protein gene from the protoscolex of Taenia multiceps.

    Science.gov (United States)

    Nie, Hua-Ming; Xie, Yue; Fu, Yan; Yang, Ying-Dong; Gu, Xiao-Bin; Wang, Shu-Xian; Peng, Xi; Lai, Wei-Ming; Peng, Xue-Rong; Yang, Guang-You

    2013-05-01

    Taenia multiceps (Cestoda: Taeniidae), a worldwide cestode parasite, is emerging as an important helminthic zoonosis due to serious or fatal central nervous system disease commonly known as coenurosis in domestic and wild ruminants including humans. Herein, a fatty acid-binding protein (FABP) gene was identified from transcriptomic data in T. multiceps. This gene, which contains a complete coding sequence, was amplified by reverse-transcriptase polymerase chain reaction. The corresponding protein, which was named TmFABP, had a molecular weight of 14 kDa, and subsequently was recombinantly expressed in Escherichia coli. The fusion protein was purified on Ni-NTA beads (Bio-Rad). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses showed that the purified recombinant protein caused immunogenicity. Immunohistochemical studies showed that TmFABP was expressed at the tegumental level in the protoscolices and in the cells between the body wall and parenchyma layer of the cestode. In sections from gravid proglottids, intense staining was detected in the uterus and eggs. Based on this, TmFABP could be switched on during differentiation of germinative layers to protoscoleces and from metacestodes to adult worms. Taken together, our results already reported for T. multiceps suggest the possibility of TmFABP developing a vaccine to control and prevent coenurosis.

  8. Single nucleotide polymorphism analysis on chicken extra-celluar fatty acid binding protein gene and its associations with fattiness trait

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Fattiness is an important parameter to estimate meat quality, which has high heritability. In this experiment, F2 chickens derived from Broilers crossing to Silky were used to study the effect of extracellular fatty acid binding protein (EX-FABP) gene on abdominal fat accumulation. 1.6 kb of the 5′ region of the gene was amplified by six pairs of primers, and then single nucleotide poly-morphisms (SNPs) were detected by the technique of single strand conformation polymorphism (SSCP) and then confirmed by sequencing. There were four nucleotides variations found, A-G at -1807, C-A at -1805, T-C at -1011 and a C insertion at -1000 respectively. The result of least square analysis suggests that the birds with BB genotype defined by the second pair of primer have a higher abdominal fat weight and abdominal fat percentage than the birds with the other genotypes (AA and AB). It implied that EX-FABP gene could be a candidate locus or linked to a major gene to significantly affect abdominal fat traits in chicken.

  9. Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.

    Science.gov (United States)

    Iwayama, Yoshimi; Hattori, Eiji; Maekawa, Motoko; Yamada, Kazuo; Toyota, Tomoko; Ohnishi, Tetsuo; Iwata, Yasuhide; Tsuchiya, Kenji J; Sugihara, Genichi; Kikuchi, Mitsuru; Hashimoto, Kenji; Iyo, Masaomi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Iwata, Nakao; Nanko, Shinichiro; Iwamoto, Kazuya; Okazaki, Yuji; Kato, Tadafumi; Yoshikawa, Takeo

    2010-03-05

    Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such as schizophrenia and bipolar disorder. To unravel PPI-controlling mechanisms, we previously performed quantitative trait loci (QTL) analysis in mice, and identified Fabp7, that encodes a brain-type fatty acid binding protein (Fabp), as a causative gene. In that study, human FABP7 showed genetic association with schizophrenia. FABPs constitute a gene family, of which members FABP5 and FABP3 are also expressed in the brain. These FABP proteins are molecular chaperons for polyunsaturated fatty acids (PUFAs) such as arachidonic and docosahexaenoic acids. Additionally, the involvement of PUFAs has been documented in the pathophysiology of schizophrenia and mood disorders. Therefore in this study, we examined the genetic roles of FABP5 and 3 in schizophrenia (N = 1,900 in combination with controls) and FABP7, 5, and 3 in bipolar disorder (N = 1,762 in the case-control set). Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease. Each FABP is relatively small and it is assumed that there are multiple regulatory elements that control gene expression. Therefore, future identification of unknown regulatory elements will be necessary to make a more detailed analysis of their genetic contribution to mental illnesses.

  10. Solution Structure and Backbone Dynamics of Human Liver Fatty Acid Binding Protein: Fatty Acid Binding Revisited

    OpenAIRE

    Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.

    2012-01-01

    Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the p...

  11. Molecular cloning and tissue expression of the fatty acid-binding protein (Es-FABP gene in female Chinese mitten crab (Eriocheir sinensis

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    He Lin

    2010-09-01

    Full Text Available Abstract Background Fatty acid-binding proteins (FABPs, small cytosolic proteins that function in the uptake and utilization of fatty acids, have been extensively studied in higher vertebrates while invertebrates have received little attention despite similar nutritional requirements during periods of reproductive activity. Results Therefore, a cDNA encoding Eriocheir sinensis FABP (Es-FABP was cloned based upon EST analysis of a hepatopancreas cDNA library. The full length cDNA was 750 bp and encoded a 131 aa polypeptide that was highly homologous to related genes reported in shrimp. The 9108 bp Es-FABP gene contained four exons that were interrupted by three introns, a genomic organization common among FABP multigene family members in vertebrates. Gene expression analysis, as determined by RT-PCR, revealed the presence of Es-FABP transcripts in hepatopancreas, hemocytes, ovary, gills, muscle, thoracic ganglia, heart, and intestine, but not stomach or eyestalk. Real-time quantitative RT-PCR analysis revealed that Es-FABP expression in ovary, hemocytes, and hepatopancreas was dependent on the status of ovarian development, with peak expression observed in January. Conclusions Evidence provided in the present report supports a role of Es-FABP in lipid transport during the period of rapid ovarian growth in E. sinensis, and indirectly confirms the participation of the hepatopancreas, ovary, and hemocytes in lipid nutrient absorption and utilization processes.

  12. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

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    Bhattacharjee Rakesh

    2010-02-01

    Full Text Available Abstract Introduction Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity. Methods A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65 and non-obese (NOB. Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135, corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped. Results Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values. Conclusions Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.

  13. Identification of polymorphism in fatty acid binding protein 3 (FABP3) gene and its association with milk fat traits in riverine buffalo (Bubalus bubalis).

    Science.gov (United States)

    Dubey, Praveen Kumar; Goyal, Shubham; Mishra, Shailendra Kumar; Arora, Reena; Mukesh, Manishi; Niranjan, Saket Kumar; Kathiravan, Periasamy; Kataria, Ranjit Singh

    2016-04-01

    The fatty acid binding protein 3 (FABP3) gene, known to be associated with fat percentage of milk and meat in bovines, was screened among swamp and riverine buffaloes for polymorphism detection and further association with milk fat contents. An SNP g.307C > T was identified in the intron 2 (+53 exon 2) region of FABP3 gene of Indian buffaloes. The SNP identified was genotyped in 692 animals belonging to 15 riverine, swamp and hybrid (riverine × swamp) buffalo populations of diverse phenotypes and utilities, by PCR-RFLP. A marked contrast was observed between the C and T allele frequencies in three types of buffaloes. The frequency of C allele ranged from 0.67 to 0.96 in pure swamp buffalo populations, with the highest in Mizoram (0.96). Whereas the frequency of T allele was high across all the Indian riverine buffalo breeds, ranging from 0.57 to 0.96. None of the genotypes at FABP3 g.307C > T locus was found to have significant association with milk fat and other production traits in Mehsana dairy buffalo breed. Our study revealed marked differences in the allele frequencies between riverine and swamp buffaloes at FABP3 g.307C > T locus, without any significant association with different milk traits in riverine buffaloes.

  14. Sequencing of Intron 3 of Porcine Heart Fatty Acid-Binding Protein Gene%猪H-FABP基因intron3全序列测定

    Institute of Scientific and Technical Information of China (English)

    杨文平; 张家琦; 李彩桃; 王明艳; 张红梅; 李超; 曹果清; 周忠孝

    2012-01-01

    [目的]为将H-FABP基因应用于猪育种过程中的标记辅助选择提供基础资料.[方法]根据GenBank数据库上公开发表的相关的猪H-FABP基因序列设计特异性扩增引物,对H-FABP基因内含子3的PCR产物纯化后直接进行测序.[结果]成功扩增出猪H-FABP基因intron 3的全序列,全长为1 350 bp,已向GenBank数据库提交,检索号为DQ 002993.[结论]该研究为确定影响肌内脂肪沉积的主效基因奠定了理论基础.%[ Objective ]The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid-binding protein (H-FABP) gene. [Method]According to the related sequences of porcine H-FABP gene released in GenBank,specific primers were designed to amplify the intron 3 of porcine H-FABP gene. [ Result] The intron 3 of porcine H-FABP gene was amplified successfully. Its whole sequence was 1 350 bp in length and had been submitted to GenBank (Accesion no. :DQ 002993). [Conclusion] The study lays a theoretical foundation for deter ruination of the major genes affecting intramuscular fat deposition.

  15. Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent.

    Science.gov (United States)

    Landrier, Jean-François; Thomas, Charles; Grober, Jacques; Duez, Hélène; Percevault, Frédéric; Souidi, Maâmar; Linard, Christine; Staels, Bart; Besnard, Philippe

    2004-10-29

    Statins are drugs widely used in humans to treat hypercholesterolemia. Statins act by inhibiting cholesterol synthesis resulting in the activation of the transcription factor sterol-responsive element-binding protein-2 that controls the expression of genes involved in cholesterol homeostasis. Statin therapy also decreases plasma triglyceride and non-esterified fatty acid levels, but the mechanism behind this effect remains more elusive. Liver fatty acid-binding protein (L-FABP) plays a role in the influx of long-chain fatty acids into hepatocytes. Here we show that L-FABP is a target for statins. In rat hepatocytes, simvastatin treatment induced L-FABP mRNA levels in a dose-dependent manner. Moreover, L-FABP promoter activity was induced by statin treatment. Progressive 5'-deletion analysis revealed that the peroxisome proliferator-activated receptor (PPAR)-responsive element located at position -67/-55 was responsible for the statin-mediated transactivation of the rat L-FABP promoter. Moreover, treatment with simvastatin and the PPARalpha agonist Wy14,649 resulted in a synergistic induction of L-FABP expression (mRNA and protein) in rat Fao hepatoma cells. This effect was also observed in vivo in wild-type mice but not in PPARalpha-null animals demonstrating the direct implication of PPARalpha in L-FABP regulation by statin treatment. Statin treatment resulted in a rise in PPARalpha mRNA levels both in vitro and in vivo and activated the mouse PPARalpha promoter in a reporter assay. Altogether, these data demonstrate that L-FABP expression is up-regulated by statins through a mechanism involving PPARalpha. Moreover, PPARalpha might be a statin target gene. These effects might contribute to the triglyceride/non-esterified fatty acid-lowering properties of statins.

  16. Echinococcus granulosus fatty acid binding proteins subcellular localization.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2016-05-01

    Two fatty acid binding proteins, EgFABP1 and EgFABP2, were isolated from the parasitic platyhelminth Echinococcus granulosus. These proteins bind fatty acids and have particular relevance in flatworms since de novo fatty acids synthesis is absent. Therefore platyhelminthes depend on the capture and intracellular distribution of host's lipids and fatty acid binding proteins could participate in lipid distribution. To elucidate EgFABP's roles, we investigated their intracellular distribution in the larval stage by a proteomic approach. Our results demonstrated the presence of EgFABP1 isoforms in cytosolic, nuclear, mitochondrial and microsomal fractions, suggesting that these molecules could be involved in several cellular processes.

  17. Predicting nucleic acid binding interfaces from structural models of proteins.

    Science.gov (United States)

    Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael

    2012-02-01

    The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure.

  18. A radial glia gene marker, fatty acid binding protein 7 (FABP7, is involved in proliferation and invasion of glioblastoma cells.

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    Antonella De Rosa

    Full Text Available Glioblastoma multiforme (GBM is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS in vitro, and seem to mirror the genetic features of the original tumor better than glioma cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7 was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the role of FABP7 expression in GBM migration and provide translational hints on the timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution.

  19. Correlation between Heart-type Fatty Acid-binding Protein Gene Polymorphism and mRNA Expression with Intramuscular Fat in Baicheng-oil Chicken.

    Science.gov (United States)

    Wang, Yong; He, Jianzhong; Yang, Wenxuan; Muhantay, Gemenggul; Chen, Ying; Xing, Jinming; Liu, Jianzhu

    2015-10-01

    This study aims to determine the polymorphism and mRNA expression pattern of the heart-type fatty acid-binding protein (H-FABP) gene and their association with intramuscular fat (IMF) content in the breast and leg muscles of Baicheng oil chicken (BOC). A total of 720 chickens, including 240 black Baicheng oil chicken (BBOC), 240 silky Baicheng oil chicken (SBOC), and 240 white Baicheng oil chicken (WBOC) were raised. Three genotypes of H-FABP gene second extron following AA, AB, and BB were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) strategy. The G939A site created AA genotype and G956A site created BB genotype. The content of IMF in AA genotype in breast muscle of BBOC was significantly higher than that of AB (p = 0.0176) and the genotype in leg muscle of WBOC was significantly higher than that of AB (p = 0.0145). The G939A site could be taken as genetic marker for higher IMF content selecting for breast muscle of BBOC and leg muscle of WBOC. The relative mRNA expression of H-FABP was measured by real-time PCR at 30, 60, 90, and 120 d. The IMF content significantly increased with age in both muscles. The mRNA expression level of H-FABP significantly decreased with age in both muscles of the three types of chickens. Moreover, a significant negative correlation between H-FABP abundance and IMF content in the leg muscles of WBOC (p = 0.035) was observed. The mRNA expression of H-FABP negatively correlated with the IMF content in both breast and leg muscles of BOC sat slaughter time.

  20. Diverse roles of the nucleic acid binding protein KHSRP in cell differentiation and disease

    Science.gov (United States)

    Briata, Paola; Bordo, Domenico; Puppo, Margherita; Gorlero, Franco; Rossi, Martina; Bizzozzero, Nora Perrone; Gherzi, Roberto

    2015-01-01

    The single-stranded nucleic acid binding protein KHSRP (KH-Type Splicing Regulatory Protein) modulates RNA life and gene expression at various levels. KHSRP controls important cellular functions as different as proliferation, differentiation, metabolism and response to infectious agents. We summarize and discuss experimental evidence providing a potential link between changes in KHSRP expression/function and human diseases including neuromuscular disorders, obesity, type II diabetes, and cancer. PMID:26708421

  1. Retinoic acid binding protein in normal and neopolastic rat prostate.

    Science.gov (United States)

    Gesell, M S; Brandes, M J; Arnold, E A; Isaacs, J T; Ueda, H; Millan, J C; Brandes, D

    1982-01-01

    Sucrose density gradient analysis of cytosol from normal and neoplastic rat prostatic tissues exhibited a peak of (3H) retinoic acid binding in the 2S region, corresponding to the cytoplasmic retinoic acid binding protein (cRABP). In the Fisher-Copenhagen F1 rat, cRABP was present in the lateral lobe, but could not be detected in the ventral nor in the dorsal prostatic lobes. Four sublines of the R-3327 rat prostatic tumor contained similar levels of this binding protein. The absence of cRABP in the normal tissue of origin of the R-3327 tumor, the rat dorsal prostate, and reappearance in the neoplastic tissues follows a pattern described in other human and animal tumors. The occurrence of cRABP in the well-differentiated as well as in the anaplastic R-3327 tumors in which markers which reflect a state of differentiation and hormonal regulation, such as androgen receptor, 5 alpha reductase, and secretory acid phosphatase are either markedly reduced or absent, points to cRABP as a marker of malignant transformation.

  2. The clinical significance of fatty acid binding proteins

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    Barbara Choromańska

    2011-11-01

    Full Text Available Excessive levels of free fatty acids are toxic to cells. The human body has evolved a defense mechanism in the form of small cytoplasmic proteins called fatty acid binding proteins (FABPs that bind long-chain fatty acids (LCFA, and then refer them to appropriate intracellular disposal sites (oxidation in mitochondria and peroxisomes or storage in the endoplasmic reticulum. So far, nine types of these proteins have been described, and their name refers to the place in which they were first identified or where they can be found in the greatest concentration. The most important FABPs were isolated from the liver (L-FABP, heart (H-FABP, intestine (I-FABP, brain (B-FABP, epidermis (E-FABP and adipocytes (A-FABP. Determination of H-FABP is used in the diagnosis of myocardial infarction, and L-FABP in kidney lesions of different etiologies. It is postulated that FABPs play an important role in the pathogenesis of metabolic diseases. Elevated levels of A-FABP have been found in the pericardial fat tissue and were associated with cardiac dysfunction in obese people. A rise in A-FABP has been observed in patients with type II diabetes. I-FABP is known as a marker of cell damage in the small intestine. Increased concentration of B-FABP has been associated with human brain tumors such as glioblastoma and astrocytoma, as well as with neurodegenerative diseases (Alzheimer’s, Parkinson’s and other disorders of cognitive function. The aim of this work was to present current data on the clinical significance of fatty acid binding proteins.

  3. Bile salt recognition by human liver fatty acid binding protein.

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    Favretto, Filippo; Santambrogio, Carlo; D'Onofrio, Mariapina; Molinari, Henriette; Grandori, Rita; Assfalg, Michael

    2015-04-01

    Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is prominent among FABPs for its wide ligand repertoire, which includes long-chain fatty acids as well as bile acids (BAs). In this work, we performed a detailed molecular- and atomic-level analysis of the interactions established by human L-FABP with nine BAs to understand the binding specificity for this important class of cholesterol-derived metabolites. Protein-ligand complex formation was monitored using heteronuclear NMR, steady-state fluorescence spectroscopy, and mass spectrometry. BAs were found to interact with L-FABP with dissociation constants in the narrow range of 0.6-7 μm; however, the diverse substitution patterns of the sterol nucleus and the presence of side-chain conjugation resulted in complexes endowed with various degrees of conformational heterogeneity. Trihydroxylated BAs formed monomeric complexes in which single ligand molecules occupied similar internal binding sites, based on chemical-shift perturbation data. Analysis of NMR line shapes upon progressive addition of taurocholate indicated that the binding mechanism departed from a simple binary association equilibrium, and instead involved intermediates along the binding path. The co-linear chemical shift behavior observed for L-FABP complexes with cholate derivatives added insight into conformational dynamics in the presence of ligands. The observed spectroscopic features of L-FABP/BA complexes, discussed in relation to ligand chemistry, suggest possible molecular determinants of recognition, with implications regarding intracellular BA transport. Our findings suggest that human L-FABP is a poorly selective, universal BA binder.

  4. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    Science.gov (United States)

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-08-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-binding activity. No hybridization was detected in RNA extracted from ovary, spleen, kidney, or liver, which contain relatively low levels of cellular retinoic acid-binding protein activity. Analysis of genomic clones isolated from an EcoRI bovine genomic library demonstrated that the bovine cellular retinoic acid-binding protein gene is composed of four exons and three introns. Two putative promoter sequences were identified in the cloned 5' sequence of the gene.

  5. Liver-type fatty acid binding protein interacts with hepatocyte nuclear factor 4α

    OpenAIRE

    McIntosh, Avery L.; Petrescu, Anca D.; Hostetler, Heather A.; Kier, Ann B.; Schroeder, Friedhelm

    2013-01-01

    Hepatocyte nuclear factor 4α (HNF4α) regulates liver type fatty acid binding protein (L-FABP) gene expression. Conversely as shown herein, L-FABP structurally and functionally also interacts with HNF4α. Fluorescence resonance energy transfer (FRET) between Cy3-HNF4α (donor) and Cy5-L-FABP (acceptor) as well as FRET microscopy detected L-FABP in close proximity (~80 Å) to HNF4α, binding with high affinity Kd ~250–300 nM. Circular dichroism (CD) determined that the HNF4α/L-FABP interaction alte...

  6. Biological characterization of liver fatty acid binding gene from miniature pig liver cDNA library.

    Science.gov (United States)

    Gao, Y H; Wang, K F; Zhang, S; Fan, Y N; Guan, W J; Ma, Y H

    2015-01-01

    Liver fatty acid binding proteins (L-FABP) are a family of small, highly conserved, cytoplasmic proteins that bind to long-chain fatty acids and other hydrophobic ligands. In this study, a full-length enriched cDNA library was successfully constructed from Wuzhishan miniature pig, and then the L-FABP gene was cloned from this cDNA library and an expression vector (pEGFP-N3-L-FABP) was constructed in vitro. This vector was transfected into hepatocytes to test its function. The results of western blotting analysis demonstrated that the L-FABP gene from our full-length enriched cDNA library regulated downstream genes, including the peroxisome proliferator-activated receptor family in hepatocytes. This study provides a theoretical basis and experimental evidence for the application of L-FABP for the treatment of liver injury.

  7. The human fatty acid-binding protein family: Evolutionary divergences and functions

    Directory of Open Access Journals (Sweden)

    Smathers Rebecca L

    2011-03-01

    Full Text Available Abstract Fatty acid-binding proteins (FABPs are members of the intracellular lipid-binding protein (iLBP family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16-C20 fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied.

  8. Dietary Fat Content Effects on Concentrations of Liver and Intestinal Fatty Acid Binding Proteins

    OpenAIRE

    Murakami, Hiroshi; Sakai, Yasuo; Ohta, Kazutoshi; Hatakeyama, Katsuyoshi

    1998-01-01

    Two fatty acid binding proteins, liver and intestinal, have been identified in the rat intestine. Both are thought to be closely related to the absorption and metabolism of fatty acids in the intestinal epithelium. However, the underlying mechanism is not clearly understood. The purpose of this study was therefore to investigate the roles of these two fatty acid binding proteins in the intestinal absorption of fatty acids. Rats were fed diets varying in fat content for two or four weeks. Live...

  9. Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population.

    Directory of Open Access Journals (Sweden)

    Maria Luisa Mansego

    Full Text Available SUMMARY: The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. METHODS: 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes. DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. RESULTS: One polymorphism (rs2197076 and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. CONCLUSIONS: The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

  10. A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple-negative breast cancer.

    Science.gov (United States)

    Wang, Wenmiao; Yuan, Peng; Yu, Dianke; Du, Feng; Zhu, Anjie; Li, Qing; Zhang, Pin; Lin, Dongxin; Xu, Binghe

    2016-04-05

    Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and high heterogeneity. The aim of this study was to screen patients for single-nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC. Database-derived SNPs (NextBio, Ensembl, NCBI and MirSNP) located in the 3'-untranslated regions (3'-UTRs) of genes that are differentially expressed in breast cancer were selected. The possible associations between 111 SNPs and progression risk among 323 TNBC patients were investigated using a two-step case-control study with a discovery cohort (n=162) and a validation cohort (n=161). We identified the rs1054135 SNP in the adipocyte fatty acid binding protein 4 (FABP4) gene as a predictor of TNBC recurrence. The G allele of rs1054135 was associated with a reduced risk of disease progression as well as a prolonged disease-free survival time (DFS), with a hazard ratio (HR) for recurrence in the combined sample of 0.269 [95%CI: 0.098-0.735;P=0.001]. Notably, for individuals having the rs1054135 SNP with the AA/AG genotype, the magnitude of increased tumour recurrence risk for overweight patients (BMI≥25kg/m2) was significantly elevated (HR2.53; 95%CI: 1.06-6.03). Immunohistochemical staining of adipocytes adjacent to TNBC tissues showed that the expression level of FABP4 was statistically significantly lower in patients with the rs1054135-GG genotype and those in the disease-free group (P=0.0004 and P=0.0091, respectively). These results suggested that the expression of a lipid metabolism-related gene and an important SNP in the 3'-UTR of FABP4 are associated with TNBC prognosis, which may aid in the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents.

  11. THE ASSOCIATION OF Ala54Thr VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN GENE WITH GENERAL AND REGIONAL ADIPOSE TISSUE DEPOTS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective. To ascertain the relationship between the Ala54Thr variation of FABP2 gene and general as well as regional adipose tissue depots.Subjects. 165 subjects, in which 86 were subjects with normal glucose tolerance (NGT) [age 54.45±9.80, male/female 1.05,body mass index (BMI)26.48±4.01] and 79 were subjects with non-insulin-dependent diabetes mellitus (NIDDM)(age 55.86±10.00,male/female 1.08,BMI 26.75±3.30).Design and measurements. An association study of FABP2-Ala54Thr variation detected by PCR/HhaI digestion with general and regional adipose tissue depots determined by BMI and magnetic resonance imaging [abdominal subcutaneous and visceral adipose tissue area (SA and VA) and femoral subcutaneous adipose tissue area (FA)].Results. The geneotype and allele frequencies of FABP2-Ala54Thr variation in Chinese were quite close to the frequencies in American Caucasians and Pima Indians reported in the literature. Significant difference in genotype frequency distribution was observed between FA subgroups comparisons (FA≥75cm2 versus FA<75cm2)in NIDDM subjects (X2=11.460,P=0.003),with significantly increased in Thr54-carrier[Thr54(+)]genotype frequency and Thr54 allele frequency in NIDDM subject with FA<75cm2(odd ratio for genotype was 4.62,X2=10.112,P=0.001;and for allele=2.36,X2=5.379,P=0.020).The FA in NIDDM-Thr54(+)subgroup was significantly lower than that in subjects with NIDDM-Thr54(-)sugroup(61.19±21.51cm2 versus 75.36±31.70cm2,P=0.021). Stepwise regression analysis revealed that FABP2-Thr54 genotype variation was an independent factor contributing to the variation of FA in NIDDM(P=0.003).Conclusion. FABP2 is associated with regional adipose tissue depot.The decreased femoral subcutaneous adipose tissue depot in NIDDM subjects is related to FABP2-Thr54 variant.

  12. Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein

    DEFF Research Database (Denmark)

    Rolf, B; Oudenampsen-Krüger, E; Börchers, T

    1995-01-01

    The coding part of the cDNA for bovine liver-type fatty acid binding protein (L-FABP) has been amplified by RT-PCR, cloned and used for the construction of an Escherichia coli (E. coli) expression system. The recombinant protein made up to 25% of the soluble E. coli proteins and could be isolated...

  13. Polymorphism of Adipocyte Fatty Acid-binding Protein Gene(A-FABP) in Yak (Bos grunniens)%牦牛脂肪型脂肪酸结合蛋白基因(A-FABP)多态性分析

    Institute of Scientific and Technical Information of China (English)

    曹健; 罗玉柱; 胡江; 成述儒; 杨果; 刘秀

    2012-01-01

    脂肪型脂肪酸结合蛋白(A-FABP)属脂肪酸结合蛋白家族(FABPs)成员,参与调节哺乳动物细胞内脂肪浓度,进而影响肌肉内脂肪含量(IMF),因此A-FABP可作为影响IMF的候选基因.本研究采用PCR-SSCP技术检测甘南牦牛、青海牦牛、天祝白牦牛(Bos grunniens)A-FABP基因部分第3内含子、第4外显子及部分3'-UTR区单核苷酸多态性( SNPs),分析检测区域分子遗传特征.结果表明,3类群牦牛引物扩增区域发现5种等位基因A-E;同普通牛A-FABP基因序列比对发现6处SNPs,其中第4外显子区存在c.4222A>G的同义突变;3'-UTR区c.* 94T>A只存在于牦牛群体,是其区别于普通牛的遗传特征之一.各等位基因在群体间分布差异较大,其中天祝白牦牛只发现3种等位基因,而青海牦牛发现4种等位基因,这可能与牦牛类群的地域分布及选育程度有关.3类群牦牛A-FABP基因检测位点表现为中度多态(PIC为0.29 ~0.36),有效等位基因数较高,可作为潜在的牦牛肉质性状分子标记位点.%Adipocyte fatty acid-binding protein( A-FABP) ,as a member of the fatty acid binding protein(FAB-Ps) family,play a pivotal role in regulating intracellular fat concentration and then affect intramuscular fat(IMF) in mammalian. So A-FABP was suggested as a candidate gene of IMF in some species of livestock and poultry. In this study, single nucleotide polymorphisms (SNPs) was investigated at A-FABP intron 3,exon4 and 3'-UTR in Gannan yak,Qinghai yak and Tianzhu white yak (Bos grunniens) by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) so as to analyse their molecular genetic characteristics. Five novel SSCP patterns,representing five different alleles A-E were identified in three yak populations. With alignment of the bovine (Bos tauras) and yak A-FABP allelic sequences, six SNPs including a synonymous mutation ( c. 4222A > G) at exon 4 were checked in yak. SNP c. * 94T > A in 3'-UTR of A

  14. Urinary excretion of fatty acid-binding proteins in idiopathic membranous nephropathy.

    NARCIS (Netherlands)

    Hofstra, J.M.; Deegens, J.K.J.; Steenbergen, E.J.; Wetzels, J.F.M.

    2008-01-01

    BACKGROUND: It is suggested that proteinuria contributes to progressive renal failure by inducing tubular cell injury. The site of injury is unknown. Most studies have used markers of proximal tubular cell damage. Fatty acid-binding proteins (FABPs) are intracellular carrier proteins with different

  15. Tsetse salivary gland proteins 1 and 2 are high affinity nucleic acid binding proteins with residual nuclease activity.

    Directory of Open Access Journals (Sweden)

    Guy Caljon

    Full Text Available Analysis of the tsetse fly salivary gland EST database revealed the presence of a highly enriched cluster of putative endonuclease genes, including tsal1 and tsal2. Tsal proteins are the major components of tsetse fly (G. morsitans morsitans saliva where they are present as monomers as well as high molecular weight complexes with other saliva proteins. We demonstrate that the recombinant tsetse salivary gland proteins 1&2 (Tsal1&2 display DNA/RNA non-specific, high affinity nucleic acid binding with K(D values in the low nanomolar range and a non-exclusive preference for duplex. These Tsal proteins exert only a residual nuclease activity with a preference for dsDNA in a broad pH range. Knockdown of Tsal expression by in vivo RNA interference in the tsetse fly revealed a partially impaired blood digestion phenotype as evidenced by higher gut nucleic acid, hematin and protein contents.

  16. Lack of upregulation of epidermal fatty acid binding protein in dithranol induced irritation.

    NARCIS (Netherlands)

    Kucharekova, M.; Vissers, W.H.P.M.; Schalkwijk, J.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der

    2003-01-01

    The exact role of epidermal fatty acid binding protein (E-FABP) in skin is unknown. A restoration of the barrier function may be associated with an upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in response to oxidative stress. A recent observation that dithranol induc

  17. Early Diagnosis of Intestinal Ischemia Using Urinary and Plasma Fatty Acid Binding Proteins

    NARCIS (Netherlands)

    Thuijls, Geertje; van Wijck, Kim; Grootjans, Joep; Derikx, Joep P. M.; van Bijnen, Annemarie A.; Heineman, Erik; Dejong, Cornelis H. C.; Buurman, Wim A.; Poeze, Martijn

    2011-01-01

    Objective: This study aims at improving diagnosis of intestinal ischemia, by measuring plasma and urinary fatty acid binding protein (FABP) levels. Methods: Fifty consecutive patients suspected of intestinal ischemia were included and blood and urine were sampled at time of suspicion. Plasma and uri

  18. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy

    Directory of Open Access Journals (Sweden)

    Natalia M. Bottasso Arias

    2015-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs: intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs’ expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa.

  19. Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs

    Directory of Open Access Journals (Sweden)

    Tony Velkov

    2013-01-01

    Full Text Available Fatty acid binding proteins (FABPs act as intracellular shuttles for fatty acids as well as lipophilic xenobiotics to the nucleus, where these ligands are released to a group of nuclear receptors called the peroxisome proliferator activated receptors (PPARs. PPAR mediated gene activation is ultimately involved in maintenance of cellular homeostasis through the transcriptional regulation of metabolic enzymes and transporters that target the activating ligand. Here we show that liver- (L- FABP displays a high binding affinity for PPAR subtype selective drugs. NMR chemical shift perturbation mapping and proteolytic protection experiments show that the binding of the PPAR subtype selective drugs produces conformational changes that stabilize the portal region of L-FABP. NMR chemical shift perturbation studies also revealed that L-FABP can form a complex with the PPAR ligand binding domain (LBD of PPARα. This protein-protein interaction may represent a mechanism for facilitating the activation of PPAR transcriptional activity via the direct channeling of ligands between the binding pocket of L-FABP and the PPARαLBD. The role of L-FABP in the delivery of ligands directly to PPARα via this channeling mechanism has important implications for regulatory pathways that mediate xenobiotic responses and host protection in tissues such as the small intestine and the liver where L-FABP is highly expressed.

  20. Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

    OpenAIRE

    YAN, JING; Gong, Yuewen; She, Yi-Min; Wang, Guqi; Roberts, Michael S; Burczynski, Frank J.

    2009-01-01

    Hepatocytes expressing liver fatty acid binding protein (L-FABP) are known to be more resistant to oxidative stress than those devoid of this protein. The mechanism for the observed antioxidant activity is not known. We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L-FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrup...

  1. Biochemical Roles for Conserved Residues in the Bacterial Fatty Acid-binding Protein Family.

    Science.gov (United States)

    Broussard, Tyler C; Miller, Darcie J; Jackson, Pamela; Nourse, Amanda; White, Stephen W; Rock, Charles O

    2016-03-18

    Fatty acid kinase (Fak) is a ubiquitous Gram-positive bacterial enzyme consisting of an ATP-binding protein (FakA) that phosphorylates the fatty acid bound to FakB. In Staphylococcus aureus, Fak is a global regulator of virulence factor transcription and is essential for the activation of exogenous fatty acids for incorporation into phospholipids. The 1.2-Å x-ray structure of S. aureus FakB2, activity assays, solution studies, site-directed mutagenesis, and in vivo complementation were used to define the functions of the five conserved residues that define the FakB protein family (Pfam02645). The fatty acid tail is buried within the protein, and the exposed carboxyl group is bound by a Ser-93-fatty acid carboxyl-Thr-61-His-266 hydrogen bond network. The guanidinium of the invariant Arg-170 is positioned to potentially interact with a bound acylphosphate. The reduced thermal denaturation temperatures of the T61A, S93A, and H266A FakB2 mutants illustrate the importance of the hydrogen bond network in protein stability. The FakB2 T61A, S93A, and H266A mutants are 1000-fold less active in the Fak assay, and the R170A mutant is completely inactive. All FakB2 mutants form FakA(FakB2)2 complexes except FakB2(R202A), which is deficient in FakA binding. Allelic replacement shows that strains expressing FakB2 mutants are defective in fatty acid incorporation into phospholipids and virulence gene transcription. These conserved residues are likely to perform the same critical functions in all bacterial fatty acid-binding proteins.

  2. DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer

    Science.gov (United States)

    Arellano-Ortiz, Ana L.; Salcedo-Vargas, Mauricio; Vargas-Requena, Claudia L.; López-Díaz, José A.; De la Mora-Covarrubias, Antonio; Silva-Espinoza, Juan C.; Jiménez-Vega, Florinda

    2016-01-01

    This study determined the methylation status of cellular retinoic acid-binding protein (CRABP) gene promoters and associated them with demographic characteristics, habits, and the presence of human papilloma virus (HPV) in patients with cervical cancer (CC), low and high squamous intraepithelial lesions, and no intraepithelial lesion. Women (n = 158) were selected from the Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua, Mexico. Demographic characteristics and habit information were collected. Cervical biopsy and endocervical scraping were used to determine methylation in promoter regions by methylation-specific polymerase chain reaction technique. We found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2; there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2. Methylation in CRABP1 was associated with age (≥35 years, P = 0.002), family history of cancer (P = 0.032), the presence of HPV-16 (P = 0.013), and no alcohol intake (P = 0.035). These epigenetic changes could be involved in the CC process, and CRABP1 has the potential to be a predictive molecular marker of retinoid therapy response. PMID:27867303

  3. Urinary liver-type fatty acid-binding protein change in gestational diabetes mellitus.

    Science.gov (United States)

    Fu, Wen-Jin; Wang, Du-Juan; Deng, Ren-Tang; Huang, Zhi-Hong; Chen, Mei-Lian; Jang, You-Ming; Wen, Shu; Yang, Hong-Ling; Huang, Xian-zhang

    2015-09-01

    We compared urinary liver-type fatty acid-binding protein (L-FABP) among non-pregnant and pregnant women with and without gestational diabetes mellitus (GDM). Higher urinary L-FABP was found in pregnant with and without GDM, and considerably higher urinary L-FABP was found in the GDM group compared with the non-GDM group. Hyperglycemia and anemia were related with high urinary L-FABP expression.

  4. Relationship between serum adiopocyte fatty acid binding protein and atherosclerosis in chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    吴晶

    2014-01-01

    Objective To investigate the expression of serum adiopocyte fatty acid binding protein(A-FABP)in chronic kidney disease(CKD)and the role that A-FABP plays in CKD with atherosclerosis.Methods A total of 138 patients with CKD and 20 health control volunteers(HC)were involved in this study.The levels of serum AFABP,free fatty acid(FFA),interleukin-6(IL-6),

  5. Towards an understanding of Mesocestoides vogae fatty acid binding proteins' roles.

    Directory of Open Access Journals (Sweden)

    Gabriela Alvite

    Full Text Available Two fatty acid binding proteins, MvFABPa and MvFABPb were identified in the parasite Mesocestoides vogae (Platyhelmithes, Cestoda. Fatty acid binding proteins are small intracellular proteins whose members exhibit great diversity. Proteins of this family have been identified in many organisms, of which Platyhelminthes are among the most primitive. These proteins have particular relevance in flatworms since de novo synthesis of fatty acids is absent. Fatty acids should be captured from the media needing an efficient transport system to uptake and distribute these molecules. While HLBPs could be involved in the shuttle of fatty acids to the surrounding host tissues and convey them into the parasite, FABPs could be responsible for the intracellular trafficking. In an effort to understand the role of MvFABPs in fatty acid transport of M. vogae larvae, we analysed the intracellular localization of both MvFABPs and the co-localization with in vivo uptake of fatty acid analogue BODIPY FL C16. Immunohistochemical studies on larvae sections using specific antibodies, showed a diffuse cytoplasmic distribution of each protein with some expression in nuclei and mitochondria. MvFABPs distribution was confirmed by mass spectrometry identification from 2D-electrophoresis of larvae subcellular fractions. This work is the first report showing intracellular distribution of MvFABPs as well as the co-localization of these proteins with the BODIPY FL C16 incorporated from the media. Our results suggest that fatty acid binding proteins could target fatty acids to cellular compartments including nuclei. In this sense, M. vogae FABPs could participate in several cellular processes fulfilling most of the functions attributed to vertebrate's counterparts.

  6. Heart-type fatty-acid-binding protein (FABP3 is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Directory of Open Access Journals (Sweden)

    Ryoko Tsukahara

    2014-01-01

    Full Text Available Fatty-acid-binding protein 3, muscle and heart (FABP3, also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs. In this study, using lysophosphatidic acid (LPA-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs. Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA. We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus.

  7. Assessment of coronary reperfusion in patients with myocardial infarction using fatty acid binding protein concentrations in plasma

    NARCIS (Netherlands)

    M.J.M. de Groot; A.M.M. Muijtjens; M.L. Simoons (Maarten); W.T. Hermens (Wim); J.F.C. Glatz

    2001-01-01

    textabstractOBJECTIVE: To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes

  8. Identification of a fatty acid binding protein4-UCP2 axis regulating microglial mediated neuroinflammation.

    Science.gov (United States)

    Duffy, Cayla M; Xu, Hongliang; Nixon, Joshua P; Bernlohr, David A; Butterick, Tammy A

    2017-02-16

    Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism. Despite the widespread appreciation for the role of FABP4 in mediating peripheral inflammation, the expression of FABP4 and a potential FABP4-UCP2 axis regulating microglial inflammatory capacity is largely uncharacterized. To that end, we hypothesized that microglial cells express FABP4 and that inhibition would upregulate UCP2 and attenuate palmitic acid (PA)-induced pro-inflammatory response. Gene expression confirmed expression of FABP4 in brain tissue lysate from C57Bl/6J mice and BV2 microglia. Treatment of microglial cells with an FABP inhibitor (HTS01037) increased expression of Ucp2 and arginase in the presence or absence of PA. Moreover, cells exposed to HTS01037 exhibited attenuated expression of inducible nitric oxide synthase (iNOS) compared to PA alone indicating reduced NFκB signaling. Hypothalamic tissue from mice lacking FABP4 exhibit increased UCP2 expression and reduced iNOS, tumor necrosis factor-alpha (TNF-α), and ionized calcium-binding adapter molecule 1 (Iba1; microglial activation marker) expression compared to wild type mice. Further, this effect is negated in microglia lacking UCP2, indicating the FABP4-UCP2 axis is pivotal in obesity induced neuroinflammation. To our knowledge, this is the first report demonstrating a FABP4-UCP2 axis with the potential to modulate the microglial inflammatory response.

  9. Ligand specificity and conformational stability of human fatty acid-binding proteins.

    Science.gov (United States)

    Zimmerman, A W; van Moerkerk, H T; Veerkamp, J H

    2001-09-01

    Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. At least eight different types of FABP occur, each with a specific tissue distribution and possibly with a distinct function. To define the functional characteristics of all eight human FABPs, viz. heart (H), brain (B), myelin (M), adipocyte (A), epidermal (E), intestinal (I), liver (L) and ileal lipid-binding protein (I-LBP), we studied their ligand specificity, their conformational stability and their immunological crossreactivity. Additionally, binding of bile acids to I-LBP was studied. The FABP types showed differences in fatty acid binding affinity. Generally, the affinity for palmitic acid was lower than for oleic and arachidonic acid. All FABP types, except E-FABP, I-FABP and I-LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS). Only L-FABP, I-FABP and M-FABP showed binding of 11-((5-dimethylaminonaphtalene-1-sulfonyl)amino)undecanoic acid (DAUDA). I-LBP showed increasing binding of bile acids in the order taurine-conjugated>glycine-conjugated>unconjugated bile acids. A hydroxylgroup of bile acids at position 7 decreased and at position 12 increased the binding affinity to I-LBP. The fatty acid-binding affinity and the conformation of FABP types were differentially affected in the presence of urea. Our results demonstrate significant differences in ligand binding, conformational stability and surface properties between different FABP types which may point to a specific function in certain cells and tissues. The preference of I-LBP (but not L-FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum.

  10. Association of the heart fatty acid-binding protein gene with quality of carcass and meat traits in pigs Associação entre o gene da proteína de ligação de ácidos graxos - coração com características de carcaça e qualidade da carne em suínos

    OpenAIRE

    Figueiredo, F C; P.S. Lopes; A.P.G. Pinto; Paiva,D.A.F.; Mendonça,P.T.; GUIMARÃES, S. E. F.

    2008-01-01

    The heart fatty acid-binding protein (HFABP) gene was sequenced in parental animals of a F2 crossing of boars of the Brazilian native Piau breed with commercial sows (Landrace x Large White Pietrain). Primers used for PCR were designed to amplify four exons of the gene. The PCR products were sequenced and compared with the GenBank sequences. Differences between the generated sequences and the GenBank sequences were observed for both genetic groups. A total of 246 F2 animals were genotyped usi...

  11. Model of β-Sheet of Muscle Fatty Acid Binding Protein of Locusta migratoria Displays Characteristic Topology.

    Science.gov (United States)

    Kizilbash, Nadeem A; Hai, Abdul; Alruwaili, Jamal

    2013-01-01

    The β-sheet of muscle fatty acid binding protein of Locusta migratoria (Lm-FABP) was modeled by employing 2-D NMR data and the Rigid Body Assembly method. The model shows the β-sheet to comprise ten β-strands arranged anti-parallel to each other. There is a β-bulge between Ser 13 and Gln 14 which is a difference from the published structure of β-sheet of bovine heart Fatty Acid Binding Protein. Also, a hydrophobic patch consisting of Ile 45, Phe 51, Phe 64 and Phe 66 is present on the surface which is characteristic of most Fatty Acid Binding Proteins. A "gap" is present between βD and βE that provides evidence for the presence of a portal or opening between the polypeptide chains which allows ligand fatty acids to enter the protein cavity and bind to the protein.

  12. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.

    Science.gov (United States)

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina

    2016-08-01

    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  13. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  14. Molecular characterization, tissue expression, and polymorphism analysis of liver-type fatty acid binding protein in Landes geese.

    Science.gov (United States)

    Song, Z; Shao, D; Sun, X X; Niu, J W; Gong, D Q

    2015-01-01

    Liver weight is an important economic trait in the fatty goose liver industry. Liver-type fatty acid binding protein (L-FABP) is involved in the formation and metabolism of fatty acids. Thus, we hypothesized that sequence polymorphisms in L-FABP were associated with fatty liver weight in goose. We first isolated, sequenced, and characterized the goose L-FABP gene, which had not been previously reported. The goose L-FABP gene was 2490 bp and included 4 exons coding for a 126-amino acid protein. Analysis of expression levels of the goose L-FABP gene in different tissues showed that the expression level in the liver tissue was higher than in other tissues, and was significantly higher in the liver tissue of overfed geese than in control geese. Moreover, a single nucleotide polymorphism located at 774 bp in the gene was identified in a Landes goose population. To test whether this single nucleotide polymorphism was associated with fatty liver production, liver weight and the ratio of liver to carcass weights were determined for the 3 genotypes with this single nucleotide polymorphism (TT, TG, GG) in overfed Landes geese. Our data indicate that individuals with the GG genotype had higher values for the variables measured than those with the other 2 genotypes, suggesting that L-FABP can be a selection marker for the trait of fatty liver production in goose.

  15. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    OpenAIRE

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-01-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-bindin...

  16. Recent insights into the biological functions of liver fatty acid binding protein 1.

    Science.gov (United States)

    Wang, GuQi; Bonkovsky, Herbert L; de Lemos, Andrew; Burczynski, Frank J

    2015-12-01

    Over four decades have passed since liver fatty acid binding protein (FABP)1 was first isolated. There are few protein families for which most of the complete tertiary structures, binding properties, and tissue occurrences are described in such detail and yet new functions are being uncovered for this protein. FABP1 is known to be critical for fatty acid uptake and intracellular transport and also has an important role in regulating lipid metabolism and cellular signaling pathways. FABP1 is an important endogenous cytoprotectant, minimizing hepatocyte oxidative damage and interfering with ischemia-reperfusion and other hepatic injuries. The protein may be targeted for metabolic activation through the cross-talk among many transcriptional factors and their activating ligands. Deficiency or malfunction of FABP1 has been reported in several diseases. FABP1 also influences cell proliferation during liver regeneration and may be considered as a prognostic factor for hepatic surgery. FABP1 binds and modulates the action of many molecules such as fatty acids, heme, and other metalloporphyrins. The ability to bind heme is another cytoprotective property and one that deserves closer investigation. The role of FABP1 in substrate availability and in protection from oxidative stress suggests that FABP1 plays a pivotal role during intracellular bacterial/viral infections by reducing inflammation and the adverse effects of starvation (energy deficiency).

  17. Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4.

    Science.gov (United States)

    Gorbenko, O; Panayotou, G; Zhyvoloup, A; Volkova, D; Gout, I; Filonenko, V

    2010-04-01

    PTEN is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. Recent studies have also demonstrated that PTEN is a promising target in type II diabetes and obesity treatment. Using C-terminal PTEN sequence in pEG202-NLS as bait, yeast two-hybrid screening on Mouse Embryo, Colon Cancer, and HeLa cDNA libraries was carried out. Isolated positive clones were validated by mating assay and identified through automated DNA sequencing and BLAST database searches. Sequence analysis revealed a number of PTEN-binding proteins linking this phosphatase to a number of different signaling cascades, suggesting that PTEN may perform other functions besides tumor-suppressing activity in different cell types. In particular, the interplay between PTEN function and adipocyte-specific fatty-acid-binding protein FABP4 is of notable interest. The demonstrable tautology of PTEN to FABP4 suggested a role for this phosphatase in the regulation of lipid metabolism and adipocyte differentiation. This interaction was further studied using coimmunoprecipitation and gel-filtration assays. Finally, based on Biacore assay, we have calculated the K(D) of PTEN-FABP4 complex, which is around 2.8 microM.

  18. Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1 Proteins: Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus

    Directory of Open Access Journals (Sweden)

    Christine Winter

    2013-07-01

    Full Text Available The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV and the spike protein of infectious bronchitis virus (IBV. Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.

  19. Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis.

    NARCIS (Netherlands)

    Reisinger, K.W.; Zee, D.C. van der; Brouwers, H.A.A.; Kramer, B.W.; Heurn, L.W.E. van; Buurman, W.A.; Derikx, J.P.

    2012-01-01

    BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, s

  20. Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis

    NARCIS (Netherlands)

    Reisinger, Kostan W.; Van der Zee, David C.; Brouwers, Hens A. A.; Kramer, Boris W.; van Heurn, L. W. Ernest; Buurman, Wim A.; Derikx, Joep P. M.

    2012-01-01

    Background: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, s

  1. Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Sugaya, Takeshi; Hovind, Peter;

    2010-01-01

    Urinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predict...

  2. Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Sugaya, Takeshi; Hovind, Peter;

    2010-01-01

    Urinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predictor...

  3. Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study

    NARCIS (Netherlands)

    Schurink, M.; Kooi, E.M.; Hulzebos, C.V.; Kox, R.G.; Groen, H.; Heineman, E.; Bos, A.F; Hulscher, J.B.

    2015-01-01

    BACKGROUND: Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial w

  4. Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke

    DEFF Research Database (Denmark)

    Holm, Sverre; Ueland, Thor; Dahl, Tuva B

    2011-01-01

    Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke....

  5. Seasonal dynamics of flight muscle fatty acid binding protein and catabolic enzymes in a migratory shorebird.

    Science.gov (United States)

    Guglielmo, Christopher G; Haunerland, Norbert H; Hochachka, Peter W; Williams, Tony D

    2002-05-01

    We developed an ELISA to measure heart-type fatty acid binding protein (H-FABP) in muscles of the western sandpiper (Calidris mauri), a long-distance migrant shorebird. H-FABP accounted for almost 11% of cytosolic protein in the heart. Pectoralis H-FABP levels were highest during migration (10%) and declined to 6% in tropically wintering female sandpipers. Premigratory birds increased body fat, but not pectoralis H-FABP, indicating that endurance flight training may be required to stimulate H-FABP expression. Juveniles making their first migration had lower pectoralis H-FABP than adults, further supporting a role for flight training. Aerobic capacity, measured by citrate synthase activity, and fatty acid oxidation capacity, measured by 3-hydroxyacyl-CoA-dehydrogenase and carnitine palmitoyl transferase activities, did not change during premigration but increased during migration by 6, 12, and 13%, respectively. The greater relative induction of H-FABP (+70%) with migration than of catabolic enzymes suggests that elevated H-FABP is related to the enhancement of uptake of fatty acids from the circulation. Citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and carnitine palmitoyl transferase were positively correlated within individuals, suggesting coexpression, but enzyme activities were unrelated to H-FABP levels.

  6. [L-type fatty acid binding protein (L-FABP) and kidney disease].

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Kimura, Kenjiro

    2014-02-01

    Liver-type fatty acid binding protein (L-FABP) is expressed in the cytoplasm of human renal proximal tubules. Renal L-FABP expression is up-regulated and urinary excretion of renal L-FABP is increased by various stressors, such as urinary protein, hyperglycemia, tubular ischemia, toxins, and salt-sensitive hypertension, which lead to the progression of kidney disease. Urinary L-FABP levels accurately reflect the degree of tubulointerstitial damage and are strongly correlated with the prognosis of chronic kidney disease (CKD) patients in clinical studies. In patients with type I or type II diabetes, urinary L-FABP levels were reported to be significantly higher in patients with normal levels of urinary albumin than in those with microalbuminuria. Urinary L-FABP may be useful for the early detection of diabetic nephropathy. Furthermore, in a longitudinal study, a higher level of urinary L-FABP was found to be a risk factor for the progression of diabetic nephropathy. With respect to acute kidney disease (AKI), urinary L-FABP facilitates the early detection of AKI before an increase in serum creatinine. Therefore, urinary L-FABP was approved as a new tubular biomarker by the Ministry of Health, Labour and Welfare of Japan.

  7. Fatty-acid binding proteins modulate sleep and enhance long-term memory consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason R Gerstner

    Full Text Available Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7 on sleep and long-term memory (LTM formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation "window" that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.

  8. Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation.

    Science.gov (United States)

    Ehara, Haruhiko; Makino, Marie; Kodama, Koichiro; Konoki, Keiichi; Ito, Takuhiro; Sekine, Shun-ichi; Fukuzawa, Seketsu; Yokoyama, Shigeyuki; Tachibana, Kazuo

    2015-07-06

    Okadaic acid (OA) is a marine polyether cytotoxin that was first isolated from the marine sponge Halichondria okadai. OA is a potent inhibitor of protein serine/threonine phosphatases (PP) 1 and 2A, and the structural basis of phosphatase inhibition has been well investigated. However, the role and mechanism of OA retention in the marine sponge have remained elusive. We have solved the crystal structure of okadaic acid binding protein 2.1 (OABP2.1) isolated from H. okadai; it has strong affinity for OA and limited sequence homology to other proteins. The structure revealed that OABP2.1 consists of two α-helical domains, with the OA molecule deeply buried inside the protein. In addition, the global fold of OABP2.1 was unexpectedly similar to that of aequorin, a jellyfish photoprotein. The presence of structural homologues suggested that, by using similar protein scaffolds, marine invertebrates have developed diverse survival systems adapted to their living environments.

  9. Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia.

    Directory of Open Access Journals (Sweden)

    Martin Kaczocha

    Full Text Available The endocannabinoid anandamide (AEA is an antinociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by fatty acid amide hydrolase (FAAH. Fatty acid binding proteins (FABPs are intracellular carriers that deliver AEA and related N-acylethanolamines (NAEs to FAAH for hydrolysis. The mammalian brain expresses three FABP subtypes: FABP3, FABP5, and FABP7. Recent work from our group has revealed that pharmacological inhibition of FABPs reduces inflammatory pain in mice. The goal of the current work was to explore the effects of FABP inhibition upon nociception in diverse models of pain. We developed inhibitors with differential affinities for FABPs to elucidate the subtype(s that contributes to the antinociceptive effects of FABP inhibitors. Inhibition of FABPs reduced nociception associated with inflammatory, visceral, and neuropathic pain. The antinociceptive effects of FABP inhibitors mirrored their affinities for FABP5, while binding to FABP3 and FABP7 was not a predictor of in vivo efficacy. The antinociceptive effects of FABP inhibitors were mediated by cannabinoid receptor 1 (CB1 and peroxisome proliferator-activated receptor alpha (PPARα and FABP inhibition elevated brain levels of AEA, providing the first direct evidence that FABPs regulate brain endocannabinoid tone. These results highlight FABPs as novel targets for the development of analgesic and anti-inflammatory therapeutics.

  10. Common FABP4 Genetic Variants and Plasma Levels of Fatty Acid Binding Protein 4 in Older Adults

    Science.gov (United States)

    Mukamal, Kenneth J.; Wilk, Jemma B.; Biggs, Mary L.; Jensen, Majken K.; Ix, Joachim H.; Kizer, Jorge R.; Tracy, Russell P.; Zieman, Susan J.; Mozaffarian, Dariush; Psaty, Bruce M.; Siscovick, David S.; Djoussé, Luc

    2013-01-01

    We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p ≤ 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3′untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels. PMID:24043587

  11. The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus

    Directory of Open Access Journals (Sweden)

    Enjuanes Luis

    2011-09-01

    Full Text Available Abstract Background Transmissible gastroenteritis virus (TGEV has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. Methods The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. Results Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3 deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. Conclusions Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.

  12. 大豆水杨酸结合蛋白基因GmSABP2的克隆及功能分析%Cloning and Function Analysis of Salicylic Acid Binding Protein Gene GmSABP2 from Soybean

    Institute of Scientific and Technical Information of China (English)

    贾亚军; 王晓婷; 许娜; 郭娜; 邢邯

    2015-01-01

    株的种子萌发率为38%,12 d大小幼苗主根长为0.4 cm,成熟植株的存活率为49%;转基因株系的种子萌发率为67%,12 d大小幼苗主根长为1.1 cm,成熟植株的存活率为78%.在模拟干旱(20% PEG6000)处理条件下,野生型植株的种子萌发率为31%,12 d大小幼苗主根长为0.5 cm,成熟植株的存活率为36%;转基因株系的种子萌发率为57%,12 d大小幼苗主根长为1.0 cm,成熟植株的存活率为66%.[结论]GmSABP2在拟南芥植株对盐和干旱的抗性中有一定的作用.%[Objective]The aim of this study is to clone and analyze soybean protein gene GmSABP2, which is binded with salicylic acid, and transform Arabidopsis for analyzing salt tolerance and drought tolerance, and further understand the molecular mechanism of salt tolerance and drought-resistance of the gene.[Method] Using SABP2 in Arabidopsis thaliana as a probe, the soybean genome database was searched, and the highest sequence homology was picked out and named as GmSABP2. The gene GmSABP2 was cloned by using electronic cloning technology. The DNAMAN program was used to analyze the amino acid sequence alignment and the conserved domain amino acid by the CD-search conducted NCBI. The MEGA program was applied to make the phylogenetic analysis. The phenotypic variation of soybean seedlings under salt and drought stress was analyzed. The expression of the characteristics of GmSABP2 under salt and drought conditions was analyzed by Real time-PCR of soybean seedlings. Gateway technology was used to build plant expression vector pEarleyGate103-GmSABP2, shifted into Agrobacterium tumefaciens EHA105, infected Arabidopsis by utilizing flower dip method, then the homozygous transgenic plants were obtained by resistance screening and finally the salt and drought tolerance was analyzed. The wild-type plants and transgenic plants were treated under salt and drought stresses, and both the seed germination, root length and mature plants were counted under stress conditions.[Result]The c

  13. Light microscopic immunocytochemical localization of hepatic and intestinal types of fatty acid-binding proteins in rat small intestine.

    Science.gov (United States)

    Shields, H M; Bates, M L; Bass, N M; Best, C J; Alpers, D H; Ockner, R K

    1986-05-01

    Monospecific antisera to purified hepatic fatty acid-binding protein (hFABP) and gut fatty acid-binding protein (gFABP) have been used to localize these two proteins in the small intestine of fed rats at the light microscopic level. Pieces of duodenum, jejunum, and ileum were removed from 4-, 10-, 20-, 22-, and 60-day-old Sprague-Dawley rats. Both cryostat and paraffin sections were studied for the presence of hFABP or gFABP by the avidin-biotin immunoperoxidase method. Slides were graded blind for the intensity of staining. Despite the structural and immunological differences between these two proteins, we showed no major differences between their staining patterns or their staining intensity throughout the intestine during postnatal development. The staining for both fatty acid-binding proteins was cytoplasmic. No brush border staining was found. Staining was more intense in the proximal rather than distal intestine, in the villus rather than crypt cells, and in the apex rather than the base of intestinal cells. Shifts in staining patterns, and staining intensity occurring during development may be related to variations in dietary fat intake, rates of cell proliferation, intestinal anatomy, and mechanisms for fat absorption.

  14. Crystal structure of axolotl (Ambystoma mexicanum) liver bile acid-binding protein bound to cholic and oleic acid.

    Science.gov (United States)

    Capaldi, Stefano; Guariento, Mara; Perduca, Massimiliano; Di Pietro, Santiago M; Santomé, José A; Monaco, Hugo L

    2006-07-01

    The family of the liver bile acid-binding proteins (L-BABPs), formerly called liver basic fatty acid-binding proteins (Lb-FABPs) shares fold and sequence similarity with the paralogous liver fatty acid-binding proteins (L-FABPs) but has a different stoichiometry and specificity of ligand binding. This article describes the first X-ray structure of a member of the L-BABP family, axolotl (Ambystoma mexicanum) L-BABP, bound to two different ligands: cholic and oleic acid. The protein binds one molecule of oleic acid in a position that is significantly different from that of either of the two molecules that bind to rat liver FABP. The stoichiometry of binding of cholate is of two ligands per protein molecule, as observed in chicken L-BABP. The cholate molecule that binds buried most deeply into the internal cavity overlaps well with the analogous bound to chicken L-BABP, whereas the second molecule, which interacts with the first only through hydrophobic contacts, is more external and exposed to the solvent.

  15. Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bassuk, J.A.; Tsichlis, P.N.; Sorof, S.

    1987-11-01

    Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene). The level of immunohistochemically detected p14 was low when growth activity of hepatocytes was low, was markedly elevated during mitosis in normal and regenerating livers, but was very high throughout interphase during proliferation of hyperplastic and malignant hepatocytes induced in rat liver by a carcinogen (N-2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene). The authors report here that p14 is the liver fatty acid binding protein. The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage lambdagt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein. Furthermore, the two proteins shared the following properties: size of mRNA, amino acid composition, molecular size according to NaDodSO/sub 4/ gel electrophoresis, and electrophoretic mobilities in a Triton X-100/acetic acid/urea gel. The two polypeptides bound oleic acid similarly. Finally, identical elevations of cytoplasmic immunostain were detected specifically in mitotic hepatocytes with either antiserum. The collected findings are suggestive that liver fatty acid binding protein may carry ligands that promote hepatocyte division and may transport certain activated chemical carcinogens.

  16. Sex Steroid Modulation of Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

    Science.gov (United States)

    Ockner, Robert K.; Lysenko, Nina; Manning, Joan A.; Monroe, Scott E.; Burnett, David A.

    1980-01-01

    The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated. In previous studies we showed that [14C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males. The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females. These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis. In the present studies, sex steroid effects on hepatocyte [14C]oleate utilization and FABP concentration were investigated directly. Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [14C]oleate utilization. With maturation, total [14C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d. Fatty acid oxidation was little affected. Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [14C]oleate utilization was studied. Castration virtually eliminated maturational changes and blunted the sex differences in adults. Estradiol or testosterone largely reproduced the appropriate adult pattern of [14C]oleate utilization regardless of the genotypic sex of the treated animal. In immature females and males, total cytosolic FABP concentrations were similar. In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [14C]oleate utilization (r = 0.91) and incorporation into triglycerides (r = 0.94) on the other. In 30-d-old animals rates of [14C

  17. Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

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    Yusuke Okazaki

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP, in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226 were enrolled. Urinary FABP4 (U-FABP4 and urinary albumin-to-creatinine ratio (UACR were measured. Change in estimated glomerular filtration rate (eGFR was followed up one year later.In 93 (23.7% of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4, triglycerides, hemoglobin A1c (HbA1c, urinary FABP1 (U-FABP1 and UACR (r = 0.360, p<0.001. Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

  18. Characterization of a Single-Stranded DNA-Binding-Like Protein from Nanoarchaeum equitans--A Nucleic Acid Binding Protein with Broad Substrate Specificity.

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    Marcin Olszewski

    Full Text Available SSB (single-stranded DNA-binding proteins play an essential role in all living cells and viruses, as they are involved in processes connected with ssDNA metabolism. There has recently been an increasing interest in SSBs, since they can be applied in molecular biology techniques and analytical methods. Nanoarchaeum equitans, the only known representative of Archaea phylum Nanoarchaeota, is a hyperthermophilic, nanosized, obligatory parasite/symbiont of Ignicoccus hospitalis.This paper reports on the ssb-like gene cloning, gene expression and characterization of a novel nucleic acid binding protein from Nanoarchaeum equitans archaeon (NeqSSB-like protein. This protein consists of 243 amino acid residues and one OB fold per monomer. It is biologically active as a monomer like as SSBs from some viruses. The NeqSSB-like protein displays a low sequence similarity to the Escherichia coli SSB, namely 10% identity and 29% similarity, and is the most similar to the Sulfolobus solfataricus SSB (14% identity and 32% similarity. The NeqSSB-like protein binds to ssDNA, although it can also bind mRNA and, surprisingly, various dsDNA forms, with no structure-dependent preferences as evidenced by gel mobility shift assays. The size of the ssDNA binding site, which was estimated using fluorescence spectroscopy, is 7 ± 1 nt. No salt-dependent binding mode transition was observed. NeqSSB-like protein probably utilizes a different model for ssDNA binding than the SSB proteins studied so far. This protein is highly thermostable; the half-life of the ssDNA binding activity is 5 min at 100 °C and melting temperature (T(m is 100.2 °C as shown by differential scanning calorimetry (DSC analysis.NeqSSB-like protein is a novel highly thermostable protein which possesses a unique broad substrate specificity and is able to bind all types of nucleic acids.

  19. Characterization of a Single-Stranded DNA-Binding-Like Protein from Nanoarchaeum equitans—A Nucleic Acid Binding Protein with Broad Substrate Specificity

    Science.gov (United States)

    Olszewski, Marcin; Balsewicz, Jan; Nowak, Marta; Maciejewska, Natalia; Cyranka-Czaja, Anna; Zalewska-Piątek, Beata; Piątek, Rafał; Kur, Józef

    2015-01-01

    Background SSB (single-stranded DNA-binding) proteins play an essential role in all living cells and viruses, as they are involved in processes connected with ssDNA metabolism. There has recently been an increasing interest in SSBs, since they can be applied in molecular biology techniques and analytical methods. Nanoarchaeum equitans, the only known representative of Archaea phylum Nanoarchaeota, is a hyperthermophilic, nanosized, obligatory parasite/symbiont of Ignicoccus hospitalis. Results This paper reports on the ssb-like gene cloning, gene expression and characterization of a novel nucleic acid binding protein from Nanoarchaeum equitans archaeon (NeqSSB-like protein). This protein consists of 243 amino acid residues and one OB fold per monomer. It is biologically active as a monomer like as SSBs from some viruses. The NeqSSB-like protein displays a low sequence similarity to the Escherichia coli SSB, namely 10% identity and 29% similarity, and is the most similar to the Sulfolobus solfataricus SSB (14% identity and 32% similarity). The NeqSSB-like protein binds to ssDNA, although it can also bind mRNA and, surprisingly, various dsDNA forms, with no structure-dependent preferences as evidenced by gel mobility shift assays. The size of the ssDNA binding site, which was estimated using fluorescence spectroscopy, is 7±1 nt. No salt-dependent binding mode transition was observed. NeqSSB-like protein probably utilizes a different model for ssDNA binding than the SSB proteins studied so far. This protein is highly thermostable; the half-life of the ssDNA binding activity is 5 min at 100°C and melting temperature (Tm) is 100.2°C as shown by differential scanning calorimetry (DSC) analysis. Conclusion NeqSSB-like protein is a novel highly thermostable protein which possesses a unique broad substrate specificity and is able to bind all types of nucleic acids. PMID:25973760

  20. Compartmentation of hepatic fatty-acid-binding protein in liver cells and its effect on microsomal phosphatidic acid biosynthesis.

    Science.gov (United States)

    Bordewick, U; Heese, M; Börchers, T; Robenek, H; Spener, F

    1989-03-01

    Fatty-acid-binding proteins are known to occur in the cytosol of mammalian cells and to bind fatty acids and their CoA-esters. Application of the postembedding protein A-gold labeling method with antibody against the hepatic type fatty-acid-binding protein (hFABP) to cross-sections of liver cells and a newly developed gel-chromatographic immunofluorescence assay established qualitatively (1) that hFABP in mitochondria was confined to outer mitochondrial membranes, (2) the presence of this protein in microsomes and (3) that nuclei were also filled with hFABP. Quantitative data elaborated with a non-competitive ELISA confirmed these results. A significant difference to the distribution of cardiac FABP in heart muscle cells, where this type of protein was found in cytosol, matrix and nuclei, was observed (Börchers et al. (1989) Biochim. Biophys. Acta, in the press). hFABP-containing rat liver microsomes were incubated with long-chain acyl-CoAs in the presence of hFABP (isolated from rat liver cytosol) in a study on the acylation of sn-glycerol-3-phosphate and lysophosphatidic acid. Both acyltransferases were stimulated by addition of hFABP to the incubation medium. The morphological, immunochemical as well as kinetic data infer a direct interaction of hFABP with microsomal membranes in liver cells.

  1. Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma

    OpenAIRE

    Ku, Chung-Yu; Liu, Yu-Huei; Lin, Hsuan-Yuan; Lu, Shao-Chun; Lin, Jung-Yaw

    2016-01-01

    Liver fatty acid-binding protein (L-FABP) is abundant in hepatocytes and known to be involved in lipid metabolism. Overexpression of L-FABP has been reported in various cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated L-FABP and its association with vascular endothelial growth factors (VEGFs) in 90 HCC patients. We found that L-FABP was highly expressed in their HCC tissues, and that this expression was positively correlated with tha...

  2. Heart-type fatty acid-binding protein is essential for efficient brown adipose tissue fatty acid oxidation and cold tolerance.

    Science.gov (United States)

    Vergnes, Laurent; Chin, Robert; Young, Stephen G; Reue, Karen

    2011-01-07

    Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3(-/-) mice exhibit extreme cold sensitivity despite induction of uncoupling and oxidative genes and hydrolysis of brown adipose tissue lipid stores. However, using FABP3 gain- and loss-of-function approaches in brown adipocytes, we detected a correlation between FABP3 levels and the utilization of exogenous fatty acids. Thus, Fabp3(-/-) brown adipocytes fail to oxidize exogenously supplied fatty acids, whereas enhanced Fabp3 expression promotes more efficient oxidation. These results suggest that FABP3 levels are a determinant of fatty acid oxidation efficiency by brown adipose tissue and that FABP3 represents a potential target for modulation of energy dissipation.

  3. Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine.

    Science.gov (United States)

    Gajda, Angela M; Storch, Judith

    2015-02-01

    Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte.

  4. Fatty Acid-Binding Protein in Small Intestine IDENTIFICATION, ISOLATION, AND EVIDENCE FOR ITS ROLE IN CELLULAR FATTY ACID TRANSPORT

    Science.gov (United States)

    Ockner, Robert K.; Manning, Joan A.

    1974-01-01

    A soluble fatty acid-binding protein (FABP), mol wt ∼ 12,000 is present in intestinal mucosa and other tissues that utilize fatty acids, including liver, myocardium, adipose, and kidney. This protein binds long chain fatty acids both in vivo and in vitro. FABP was isolated from rat intestine by gel filtration and isoelectric focusing. It showed a reaction of complete immunochemical identity with proteins in the 12,000 mol wt fatty acid-binding fractions of liver, myocardium, and adipose tissue supernates. (The presence of immunochemically nonidentical 12,000 mol wt FABP in these tissues is not excluded.) By quantitative radial immunodiffusion, supernatant FABP concentration in mucosa from proximal and middle thirds of jejuno-ileum significantly exceeded that in distal third, duodenum, and liver, expressed as micrograms per milligram soluble protein, micrograms per gram DNA, and micrograms per gram tissue. FABP concentration in villi was approximately three times greater than in crypts. Small quantities of FABP were present in washed nuclei-cell membrane, mitochondrial and microsomal fractions. However, the amount of FABP solubilized per milligram membrane protein was similar for all particulate fractions, and total membrane-associated FABP was only about 16% of supernatant FABP. Intestinal FABP concentration was significantly greater in animals maintained on high fat diets than on low fat; saturated and unsaturated fat diets did not differ greatly in this regard. The preponderance of FABP in villi from proximal and middle intestine, its ability to bind fatty acids in vivo as well as in vitro, and its response to changes in dietary fat intake support the concept that this protein participates in cellular fatty acid transport during fat absorption. Identical or closely related 12,000 mol wt proteins may serve similar functions in other tissues. Images PMID:4211161

  5. Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein

    Science.gov (United States)

    Hotamisligil, Gokhan S.; Johnson, Randall S.; Distel, Robert J.; Ellis, Ramsey; Papaioannou, Virginia E.; Spiegelman, Bruce M.

    1996-11-01

    Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2-/- animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.

  6. Structural and binding properties of two paralogous fatty acid binding proteins of Taenia solium metacestode.

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    Seon-Hee Kim

    Full Text Available BACKGROUND: Fatty acid (FA binding proteins (FABPs of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs of Taenia solium metacestode (TsM, a causative agent of neurocysticercosis (NC, shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: We isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2, which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15-95% with other related-members. Homology modeling demonstrated a characteristic β-barrel composed of 10 anti-parallel β-strands and two α-helices. TsMFABP2 harbored two additional loops between β-strands two and three, and β-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1 and 8.4 (TsMFABP2. Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]aminoundecannoic acid, dansyl-DL-α-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions

  7. Effect of silent adipocyte fatty acid-binding protein gene on secretion of adipocyte-synthesized triglyceride and adiponectin%沉默脂肪细胞型脂肪酸结合蛋白基因对脂肪细胞合成甘油三酯及脂联素分泌的影响

    Institute of Scientific and Technical Information of China (English)

    吴洁; 钟敏; 邹瑾

    2012-01-01

    Objective To study the effect of 3T3-L1 adipocyte fatty acid-binding protein(A-FABP) gene on secretion of adipocyte-synthesized triglyceride and adiponectin by constructing its micro RNA expression vector using RNAi technology. Methods A microRMA expression vector for A-FABP gene was constructed and transfected into 3T3-L1 adipocytes. Expression of A-FABP mRNA and protein was detected by RT-PCR and Western blot, respectively. A model of silent A-FABP gene was established. Free fatty acid(FFA) cells(0. 5 mmol/L) and mature adpocytes were incubated for 24 h and divided into control group,FFA group,RNAi group,and RNAi + FFA group. Triglyceride and adiponectin levels were measured by ELISA. Expression of A-FABP and adiponectin mRNA was detected by RT-PCR. Results The microRNA expression vector after transfected into 3T3-L1 adipocytes could significantly inhibit the expression of A-FABP mRNA and protein. The synthesis of triglyceride increased significantly while the secretion of adiponectin decreased significantly with the increasing fatty acid concentration in adipocytes(P<0. 05). The triglyceride level was significantly lower while the adiponectin secretion level and the adiponectin mRNA expression level were significantly higher in RNAi and RNAi+ groups than in control and fatty acid groups(P<0. 05). Conclusion Silent A-FABP gene may become a new target for preventing and treating atherosclerosis and diabetes mellitus.%目的 应用RNA干扰(RNAi)技术,构建针对3T3-L1脂肪细胞型脂肪酸结合蛋白(A-FABP)的microRNA表达载体,研究沉默A-FABP基因的表达对脂肪细胞合成甘油三酯及脂联素分泌的影响.方法 构建靶向A-FABP基因的microRNA表达载体转染3T3-L1脂肪细胞后,RT PCR及Western blot法检测A-FABP mRNA 及蛋白表达.建立A-FABP基因沉默细胞模型,0.5 mmol/L游离脂肪酸和成熟脂肪细胞共孵育24 h,分为对照组、脂肪酸组、RNAi组、RNAi+脂肪酸组.ELISA法分别检测甘油三酯及脂联

  8. Direct interaction between EgFABP1, a fatty acid binding protein from Echinococcus granulosus, and phospholipid membranes.

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    Jorge L Porfido

    Full Text Available BACKGROUND: Growth and maintenance of hydatid cysts produced by Echinococcus granulosus have a high requirement for host lipids for biosynthetic processes, membrane building and possibly cellular and developmental signalling. This requires a high degree of lipid trafficking facilitated by lipid transporter proteins. Members of the fatty acid binding protein (FABP family have been identified in Echinococcus granulosus, one of which, EgFABP1 is expressed at the tegumental level in the protoscoleces, but it has also been described in both hydatid cyst fluid and secretions of protoscoleces. In spite of a considerable amount of structural and biophysical information on the FABPs in general, their specific functions remain mysterious. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the way in which EgFABP1 may interact with membranes using a variety of fluorescence-based techniques and artificial small unilamellar vesicles. We first found that bacterial recombinant EgFABP1 is loaded with fatty acids from the synthesising bacteria, and that fatty acid binding increases its resistance to proteinases, possibly due to subtle conformational changes induced on EgFABP1. By manipulating the composition of lipid vesicles and the ionic environment, we found that EgFABP1 interacts with membranes in a direct contact, collisional, manner to exchange ligand, involving both ionic and hydrophobic interactions. Moreover, we observed that the protein can compete with cytochrome c for association with the surface of small unilamellar vesicles (SUVs. CONCLUSIONS/SIGNIFICANCE: This work constitutes a first approach to the understanding of protein-membrane interactions of EgFABP1. The results suggest that this protein may be actively involved in the exchange and transport of fatty acids between different membranes and cellular compartments within the parasite.

  9. Cloning, Expression and Structure Modeling Analysis of Adipocyte Fatty Acid Binding Protein Gene (FA BP4) of Sheep%绵羊脂肪细胞型脂肪酸结合蛋白基因(FABP4)cDNA的克隆、表达及其结构模拟分析

    Institute of Scientific and Technical Information of China (English)

    徐秋良; 张庆莉; 陈玉林

    2011-01-01

    For investigated the expression level of adipocyte fatty acid binding protein gene (FABP4) at different stages of sheep longissimus muscle, in this paper, the eDNA of sheep (Ovis aries) adipocyte fatty acid binding protein gene (FA BP4 ) was cloned by the method of RT-PCR using designed primer pairs of Ff and Fr according to the FA BP4 gene eDNA conservative region.The putative protein spatial structure of FABP4 was analyzed by biology software.Additionally, the expression of FABP4 in sheep longissimus muscle and the correlation between FABP4 expressions of longissimus muscle and intramuscular fat contents at different days were tested by real time RT-PCR.The results showed that the sequence of eDNA of sheep FABP4 was 464 bp containing a 399 bp of open reading frame which encoded 132 amino acids and the amino acid of FABP4 was conserved in evolution, and the FABP4 protein was assembled as a barrel conformation by two a helixes and ten 3 folds.The real time RT-PCR revealed that expressions of FABP4 in longissimus muscle from 160 and 200-day's sheep were higher than those from 90-day's (P<0.O5), respectively.The expression of FABP4 longissmus muscle at different days was positive correlated with longissimus muscle intramuscular fat contents (R2=0.1796, P<0.01).The result indicated that regulated the expression of FABP4 in sheep longissimus muscle is a potential approach for improving sheep meat quality traits.%为探讨绵羊脂肪细胞型脂肪酸结合蛋白(FABP4)在不同生长阶段背最长肌中的表达特性,本实验以成年小尾寒羊(Ovis aries)皮下脂肪组织总RNA为实验材料,在脂肪细胞型脂肪酸结合蛋白基因(FABP4)cDNA保守区域设计1对引物Ff和Fr,采用RT-PCR方法克隆了绵羊FABP4全编码序列,并运用生物软件对FABP4蛋白空间结构进行分析.同时运用实时荧光定量PCR法,对FABP4在皮下脂肪和背最长肌中的表达以及不同日龄在背最长肌中的表达量与背最长肌肌内脂肪

  10. A novel cold-regulated cold shock domain containing protein from scallop Chlamys farreri with nucleic acid-binding activity.

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    Chuanyan Yang

    Full Text Available BACKGROUND: The cold shock domain (CSD containing proteins (CSDPs are one group of the evolutionarily conserved nucleic acid-binding proteins widely distributed in bacteria, plants, animals, and involved in various cellular processes, including adaptation to low temperature, cellular growth, nutrient stress and stationary phase. METHODOLOGY: The cDNA of a novel CSDP was cloned from Zhikong scallop Chlamys farreri (designated as CfCSP by expressed sequence tag (EST analysis and rapid amplification of cDNA ends (RACE approach. The full length cDNA of CfCSP was of 1735 bp containing a 927 bp open reading frame which encoded an N-terminal CSD with conserved nucleic acids binding motif and a C-terminal domain with four Arg-Gly-Gly (RGG repeats. The CSD of CfCSP shared high homology with the CSDs from other CSDPs in vertebrate, invertebrate and bacteria. The mRNA transcripts of CfCSP were mainly detected in the tissue of adductor and also marginally detectable in gill, hepatopancreas, hemocytes, kidney, mantle and gonad of healthy scallop. The relative expression level of CfCSP was up-regulated significantly in adductor and hemocytes at 1 h and 24 h respectively after low temperature treatment (P<0.05. The recombinant CfCSP protein (rCfCSP could bind ssDNA and in vitro transcribed mRNA, but it could not bind dsDNA. BX04, a cold sensitive Escherichia coli CSP quadruple-deletion mutant, was used to examine the cold adaptation ability of CfCSP. After incubation at 17°C for 120 h, the strain of BX04 containing the vector pINIII showed growth defect and failed to form colonies, while strain containing pINIII-CSPA or pINIII-CfCSP grew vigorously, indicating that CfCSP shared a similar function with E. coli CSPs for the cold adaptation. CONCLUSIONS: These results suggest that CfCSP is a novel eukaryotic cold-regulated nucleic acid-binding protein and may function as an RNA chaperone in vivo during the cold adaptation process.

  11. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

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    Sugiyama Takayuki

    2011-07-01

    Full Text Available Abstract Background Improving the treatment of renal cell carcinoma (RCC will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7, also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC, overexpress FABP7. The abundant expression of FABP7 in primary RCCs compared to certain RCC-derived cell lines may allow the definition of the molecular components of FABP7's regulatory system. Results We determined FABP7 mRNA levels in six RCC cell lines. Two were highly expressed, whereas the other and the embryonic kidney cell line (HEK293 were weakly expressed FABP7 transcripts. Western blot analysis of the cell lines detected strong FABP7 expression only in one RCC cell line. Promoter activity in the RCC cell lines was 3- to 21-fold higher than that of HEK293. Deletion analysis demonstrated that three FABP7 promoter regions contributed to upregulated expression in RCC cell lines, but not in the HEK293 cell. Competition analysis of gel shifts indicated that OCT1, OCT6, and nuclear factor I (NFI bound to the FABP7 promoter region. Supershift experiments indicated that BRN2 (POU3F2 and NFI bound to the FABP7 promoter region as well. There was an inverse correlation between FABP7 promoter activity and BRN2 mRNA expression. The FABP7-positive cell line's NFI-DNA complex migrated faster than in other cell lines. Levels of NFIA mRNA were higher in the HEK293 cell line than in any of the six RCC cell lines. In contrast, NFIC mRNA expression was lower in the HEK293 cell line than in the six RCC cell lines. Conclusions Three putative FABP7 promoter regions drive reporter gene expression in RCC cell lines, but not in the HEK293 cell line. BRN2 and NFI may be key

  12. Expression and Characterization of Human Heart Type Fatty Acid Binding Protein in Pichia Pastoris

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    H-FABP is regarded as a tissue-specific protein existing only in myocardial cells. It is released from the cardiac tissue and gets into the plasma when a heart attack occurs; the myocardial infarction is a good case in point. As a result, the detection of H-FABP will be an early and important biomarker for the disease concerned. The objective of the study is to prepare the recombinant H-FABP by aeukaryotic expression system, pichia, to produce the protein mimicking natural H-FABP, as an immunogen for the production of the specific antibody. A gene fragment encoding H-FABP was cloned in the expressing vector pPICZα, after sequencing. The recombinant plasmid was transformed into the competent cells of the X-33 strain by means of electroporation. The expression of the target peptide indueed by methanol was screened by means of Western blotting, with the available MAb( Clone 6B6 ). Highly expressive engineer strains were obtained. The production of recombinant H-FABP under induction was about 0.7 g/L, with an Mr of 14.5 kDa and recognized by a commercially available MAb (Clone 6B6). The recombinant vector was successfully constructed. Following this, H-FABP was expressed in X-33, and it would become the source of the preparation of specific antibodies, to develop diagnostic kits.

  13. Serum high-sensitivity C-reaction protein and heart fatty acid binding protein level and cardiac accidents in patients with unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    朱红秋

    2006-01-01

    Objective To investigate the relationship between serum high-sensitivity C-reaction protein (hs-CRP) and heart fatty acid binding protein (h-FABP) on cardiac accidents in patients with unstable angina pectoris (UAP). Methods Serum levels of hs-CRP, h-FABP, cardiac troponin-Ⅰ(cTn-Ⅰ) and creatine kinase MB isoenzyme (CK-MB) were measured and cardiac accidents within 2 weeks after the test were observed in 74 patients (male

  14. An acyl-CoA-binding protein (FcACBP) and a fatty acid binding protein (FcFABP) respond to microbial infection in Chinese white shrimp, Fenneropenaeus chinensis.

    Science.gov (United States)

    Ren, Qian; Du, Zhi-Qiang; Zhao, Xiao-Fan; Wang, Jin-Xing

    2009-12-01

    Acyl-CoA-binding protein (ACBP) and fatty acid-binding protein (FABP) are involved in lipid metabolism. ACBP plays a key role in multiple cellular tasks including modulation of fatty acid biosynthesis, enzyme regulation, vesicular trafficking, and gene regulation. In our study, a 536 bp cDNA of ACBP (FcACBP) was cloned and identified as a widely distributed gene in the Chinese white shrimp, Fenneropenaeus chinensis. Its expression in intestine was upregulated in response to white spot syndrome virus (WSSV) or Vibrio anguillarum infection. The expression patterns were confirmed by Western blot analysis. FABPs, members of the lipid-binding protein superfamily, play an important role in lipid metabolism and also participate in vertebrate innate immunity. A cDNA of FABP (FcFABP) cloned from the hepatopancreas of the shrimp was 715 bp in size and encoded a 14 kDa protein. FcFABP appeared to be a basic fatty acid binding protein with a predicted isoelectric point of 9.16. It showed sequence similarity to both vertebrate and invertebrate FABPs. Phylogenetic analysis showed that FcFABP, together with LvFABP, were clustered into one group. FcFABP was detected mainly in the hepatopancreas and expression level increased after a challenge with WSSV. FcFABP was down-regulated by V. anguillarum challenge. The protein also had bacterial binding activity. These two lipid metabolism related proteins may play important roles in shrimp innate immunity.

  15. Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone.

    Science.gov (United States)

    Armas, Pablo; Nasif, Sofía; Calcaterra, Nora B

    2008-02-15

    Cellular nucleic acid binding protein (CNBP) is a small single-stranded nucleic acid binding protein made of seven Zn knuckles and an Arg-Gly rich box. CNBP is strikingly conserved among vertebrates and was reported to play broad-spectrum functions in eukaryotic cells biology. Neither its biological function nor its mechanisms of action were elucidated yet. The main goal of this work was to gain further insights into the CNBP biochemical and molecular features. We studied Bufo arenarum CNBP (bCNBP) binding to single-stranded nucleic acid probes representing the main reported CNBP putative targets. We report that, although bCNBP is able to bind RNA and single-stranded DNA (ssDNA) probes in vitro, it binds RNA as a preformed dimer whereas both monomer and dimer are able to bind to ssDNA. A systematic analysis of variant probes shows that the preferred bCNBP targets contain unpaired guanosine-rich stretches. These data expand the knowledge about CNBP binding stoichiometry and begins to dissect the main features of CNBP nucleic acid targets. Besides, we show that bCNBP presents a highly disordered predicted structure and promotes the annealing and melting of nucleic acids in vitro. These features are typical of proteins that function as nucleic acid chaperones. Based on these data, we propose that CNBP may function as a nucleic acid chaperone through binding, remodeling, and stabilizing nucleic acids secondary structures. This novel CNBP biochemical activity broadens the field of study about its biological function and may be the basis to understand the diverse ways in which CNBP controls gene expression.

  16. Heart-type Fatty Acid-binding Protein Is Essential for Efficient Brown Adipose Tissue Fatty Acid Oxidation and Cold Tolerance*

    OpenAIRE

    Vergnes, Laurent; Chin, Robert; Young, Stephen G.; Reue, Karen

    2010-01-01

    Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3−/− mice exhibit ...

  17. Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

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    Janyaporn Phuchareon

    2014-12-01

    Full Text Available Adenoid cystic carcinoma (ACC is an aggressive malignant neoplasm of the salivary glands. Its diagnosis is difficult due to overlapping features with other salivary tumors. Gene expression analysis may complement traditional diagnostic methods. We searched gene expression patterns in the Gene Expression Omnibus (GEO database and in our tumor and normal samples. The biologic and prognostic potential of the identified genes was analyzed. The GEO data set of primary xenografted ACCs revealed that expression of five genes, engrailed homeobox 1 (EN1, fatty acid binding protein 7 (FABP7, hemoglobin epsilon 1, MYB, and versican (VCAN, was dramatically increased. mRNA expression of EN1, FABP7, MYB, and VCAN distinguished our sporadic ACCs from normal tissues and benign tumors. FABP7 expression appeared to be regulated differently from EN1 and MYB and was crossly correlated with poor prognosis in our ACC cohort. Immunohistochemistry showed that FABP7 protein was predominantly expressed in the nucleus of myoepithelial cells of both tubular and cribriform subtypes. In contrast, in the solid subtype, which is often associated with a lower survival rate, FABP7 protein was uniformly expressed in cancerous cells. One case with cribriform architecture and the highest level of FABP7 mRNA showed strong FABP7 staining in both duct-type epithelial and myoepithelial cells, suggesting that diffuse expression of FABP7 protein might be related to aggressive tumor behavior and poor prognosis. We propose FABP7 as a novel biomarker in ACC. The molecule may be useful in diagnosis and for identifying more effective therapies targeting this protein or upstream molecules that regulate it.

  18. Fatty acid binding protein 7 and n-3 poly unsaturated fatty acid supply in early rat brain development.

    Science.gov (United States)

    Maximin, Elise; Langelier, Bénédicte; Aïoun, Josiane; Al-Gubory, Kaïs H; Bordat, Christian; Lavialle, Monique; Heberden, Christine

    2016-03-01

    Fatty acid binding protein 7 (FABP7), abundant in the embryonic brain, binds with the highest affinity to docosahexaenoic acid (DHA) and is expressed in the early stages of embryogenesis. Here, we have examined the consequences of the exposure to different DHA levels and of the in utero depletion of FABP7 on early rat brain development. Neurodevelopment was evaluated through the contents of two proteins, connexin 43 (Cx43) and cyclin-dependent kinase 5 (CDK5), both involved in neuroblast proliferation, differentiation, and migration. The dams were fed with diets presenting different DHA contents, from deficiency to supplementation. DHA brain embryos contents already differed at embryonic day 11.5 and the differences kept increasing with time. Cx43 and CDK5 contents were positively associated with the brain DHA levels. When FABP7 was depleted in vivo by injections of siRNA in the telencephalon, the enhancement of the contents of both proteins was lost in supplemented animals, but FABP7 depletion did not modify phospholipid compositions regardless of the diets. Thus, FABP7 is a necessary mediator of the effect of DHA on these proteins synthesis, but its role in DHA uptake is not critical, although FABP7 is localized in phospholipid-rich areas. Our study shows that high contents of DHA associated with FABP7 are necessary to promote early brain development, which prompted us to recommend DHA supplementation early in pregnancy.

  19. Association of the heart fatty acid-binding protein gene with quality of carcass and meat traits in pigs Associação entre o gene da proteína de ligação de ácidos graxos - coração com características de carcaça e qualidade da carne em suínos

    Directory of Open Access Journals (Sweden)

    F.C. Figueiredo

    2008-04-01

    Full Text Available The heart fatty acid-binding protein (HFABP gene was sequenced in parental animals of a F2 crossing of boars of the Brazilian native Piau breed with commercial sows (Landrace x Large White Pietrain. Primers used for PCR were designed to amplify four exons of the gene. The PCR products were sequenced and compared with the GenBank sequences. Differences between the generated sequences and the GenBank sequences were observed for both genetic groups. A total of 246 F2 animals were genotyped using the Hinf I restriction enzyme. Two genotypes were identified, 198 being animals HH and 48 Hh. The Hinf I SNP was significantly associated with weights of loin (bone-in (PO gene da proteína de ligação de ácidos graxos - coração foi seqüenciado em animais parentais de um cruzamento F2 entre varrões da raça nativa brasileira Piau e fêmeas comerciais (Landrace x Large White x Pietrain. Os primers utilizados na reação em cadeia da polimerase foram desenhados para amplificarem os quatro éxons do gene. Os fragmentos amplificados foram seqüenciados e comparados com a seqüência do gene depositada no GenBank. Foram observadas divergências entre as seqüências geradas e as do GenBank para ambos os grupos genéticos. Foram genotipados 246 animais F2 utilizando-se a enzima Hinf I. Dois genótipos foram identificados, sendo 198 animais HH e 48 animais Hh. O polimorfismo apresentou efeito sobre o peso total do carré (P<0,05, o peso da papada (P<0,05, o peso do filezinho (P<0,10 e o peso dos rins (P<0,01. Os resultados indicam que o gene da H-FABP apresenta potencial para aplicação em programas de seleção assistida por marcadores moleculares em suínos.

  20. Low heart-type fatty acid binding protein level during aging may protect down syndrome people against atherosclerosis

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    Vianello Elena

    2013-01-01

    Full Text Available Abstract Background Aging is considered an important independent risk factor for atherosclerosis. Down syndrome people (DS display an accelerated aging process compared to healthy subjects, anyway they are relatively resistant to developing atherosclerosis. The mechanisms involved in such protective effect are not well known. Since heart-type fatty acid binding protein (H-FABP is a protein involved in the transport of fatty acids and it has been recently correlated with the presence of atherosclerosis, we aimed to measure H-FABP level both in DS and in healthy subjects during aging to evaluate the association between this molecule, aging and atherosclerosis. Findings We quantified plasmatic H-FABP level in three groups of male DS and age-matched healthy subjects (children, age 2–14 years; adults, age 20–50 years; elderly, > 60 years using a biochip array analyzer. We observed that aging is associated with increased H-FABP level in healthy subjects but not in DS which display both the same protein level in the different ages of life and have also lower level compared to their age-matched healthy subjects. Conclusion Reduced H-FABP level during aging in DS may play a protective role against atherosclerosis. The potential involvement of H-FABP in the relationship between aging, atherosclerosis and development of coronary artery disease needs further investigations.

  1. Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

    Energy Technology Data Exchange (ETDEWEB)

    Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S. (Mount Sinai School of Medicine, New York, NY (USA)); Wada, H.; Horio, Y. (Univ. of Osaka (Japan))

    1990-05-01

    The hepatic plasma membrane fatty acid-binding protein (h-FABP{sub PM}) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP{sub PM} have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP{sub PM} reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of ({sup 3}H)oleate but not that of ({sup 35}S)sulfobromophthalein or ({sup 14}C)taurocholate. The inhibition of oleate uptake produced by anti-h-FABP{sub PM} can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP{sub PM} and mGOT are closely related.

  2. Low abdominal NIRS values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis

    Science.gov (United States)

    To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC...

  3. High Serum Adipocyte Fatty Acid Binding Protein Is Associated with Metabolic Syndrome in Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jer-Chuan Li

    2016-01-01

    Full Text Available Adipocyte fatty acid binding protein (A-FABP is a key mediator of obesity-related metabolic syndrome (MetS. The aim of this study was to evaluate the relationship between A-FABP concentration and MetS in type 2 diabetes mellitus (DM patients. Fasting blood samples were obtained from 165 type 2 DM volunteers. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Among 165 DM patients, 113 patients (68.5% had MetS. Diabetic persons who had MetS had significantly higher A-FABP levels (P<0.001 than those without MetS. Female DM persons had higher A-FABP level than man (P<0.001. No statistically significant differences in A-FABP levels were found in use of statin, fibrate, or antidiabetic drugs. Multivariate forward stepwise linear regression analysis revealed that body fat mass (P<0.001, logarithmically transformed creatinine (log-creatinine; P<0.001, female DM patients (P<0.001, and logarithmically transformed high sensitive C-reactive protein (log-hs-CRP; P=0.013 were positively correlated, while albumin (P=0.004 and glomerular filtration rate (GFR; P=0.043 were negatively correlated with serum A-FABP levels in type 2 DM patients. In this study, higher serum A-FABP level was positively associated with MetS in type 2 DM patients.

  4. Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events

    Directory of Open Access Journals (Sweden)

    Kamijo-Ikemori A

    2015-08-01

    Full Text Available Atsuko Kamijo-Ikemori,1,3 Nobuyuki Hashimoto,2 Takeshi Sugaya,1 Katsuomi Matsui,1 Mikako Hisamichi,1 Yugo Shibagaki,1 Fumihiko Miyake,2 Kenjiro Kimura1 1Department of Nephrology and Hypertension, 2Department of Cardiology, 3Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Contrast medium (CM induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP. Methods: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29. Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Results: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05 and 24 hours (P<0.005 after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17, but not in those without cardiovascular events (n=12. The parameter with the largest area under the curve (0.816 for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27–19.13; P=0.021. Conclusion: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk

  5. NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5

    Energy Technology Data Exchange (ETDEWEB)

    Volakakis, Nikolaos; Joodmardi, Eliza [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); Perlmann, Thomas, E-mail: thomas.perlmann@licr.ki.se [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); The Department of Cell and Molecular Biology, Karolinska Institute, S-17177 Stockholm (Sweden)

    2009-12-25

    The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPAR{beta}/{delta} signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPAR{beta}/{delta} and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels.

  6. Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A; Chatterjee, Amarnath; Neuman, Benjamin W; Joseph, Jeremiah S; Buchmeier, Michael J; Kuhn, Peter; Wüthrich, Kurt

    2009-12-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. Two antiparallel two-strand beta-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.

  7. Structural Insights Into Amino Acid Binding and Gene Control by a Lysine Riboswitch

    Energy Technology Data Exchange (ETDEWEB)

    Serganov, A.; Huang, L; Patel, D

    2008-01-01

    In bacteria, the intracellular concentration of several amino acids is controlled by riboswitches1, 2, 3, 4. One of the important regulatory circuits involves lysine-specific riboswitches, which direct the biosynthesis and transport of lysine and precursors common for lysine and other amino acids. To understand the molecular basis of amino acid recognition by riboswitches, here we present the crystal structure of the 174-nucleotide sensing domain of the Thermotoga maritima lysine riboswitch in the lysine-bound (1.9 A) and free (3.1 A) states. The riboswitch features an unusual and intricate architecture, involving three-helical and two-helical bundles connected by a compact five-helical junction and stabilized by various long-range tertiary interactions. Lysine interacts with the junctional core of the riboswitch and is specifically recognized through shape-complementarity within the elongated binding pocket and through several direct and K+-mediated hydrogen bonds to its charged ends. Our structural and biochemical studies indicate preformation of the riboswitch scaffold and identify conformational changes associated with the formation of a stable lysine-bound state, which prevents alternative folding of the riboswitch and facilitates formation of downstream regulatory elements. We have also determined several structures of the riboswitch bound to different lysine analogues5, including antibiotics, in an effort to understand the ligand-binding capabilities of the lysine riboswitch and understand the nature of antibiotic resistance. Our results provide insights into a mechanism of lysine-riboswitch-dependent gene control at the molecular level, thereby contributing to continuing efforts at exploration of the pharmaceutical and biotechnological potential of riboswitches.

  8. Perbedaan Kadar Liver Fatty Acid Binding Protein (L-FABP Urine Penderita Diabetes Melitus Tipe 2 dengan Normoalbuminuria dan Mikroalbuminuria

    Directory of Open Access Journals (Sweden)

    Kristina Wiharjo

    2014-06-01

    Full Text Available Diabetes mellitus (DM is the leading cause of the end stage renal disease (ESRD. Around 20−40% patients with DM develop diabetic nephropathy and eventually progress into ESRD. Type 2 DM has a greater prevalence to develop diabetic nephropathy. Oxidative stress accumulation can increase permeability of the glomerulus which results in increased urine albumin excretion, which is divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Glomerulus dysfunction occurs after tubulointerstisial renal dysfunction which decreases peritubular capillary flow that leads to tubulointerstisial hypoxia. Liver fatty acid binding protein function is to reduce hypoxia by binding oxidative stress and excretes it into urine. The aim of this study was to analyze the differences in the urine L-FABP level between normoalbuminuria and microalbuminuria type 2 DM patients. The study design was observational analytic using cross-sectional method. Subjects were 70 DM type 2 patients with normoalbuminuria (38 patients and microalbuminuria (32 patients. Statistical analysis was performed using the Mann Whitney test The results found that there were significant differences in levels of urine L-FABP between normoalbuminuria and microalbuminuria type 2 DM patients (ZM-W=3.513, p<0.001 with medians of 5 and 7 in normoalbuminuria and microalbuminuria, respectively. The urine L-FABP level increased because of the oxidative stress and hypoxia that happened before the glomerulus dysfunction. In conclusion, urine L-FABP level in patients DM type 2 with microalbuminuria is higher than that of the normoalbuminuria.

  9. Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma.

    Science.gov (United States)

    Ku, Chung-Yu; Liu, Yu-Huei; Lin, Hsuan-Yuan; Lu, Shao-Chun; Lin, Jung-Yaw

    2016-04-01

    Liver fatty acid-binding protein (L-FABP) is abundant in hepatocytes and known to be involved in lipid metabolism. Overexpression of L-FABP has been reported in various cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated L-FABP and its association with vascular endothelial growth factors (VEGFs) in 90 HCC patients. We found that L-FABP was highly expressed in their HCC tissues, and that this expression was positively correlated with that of VEGF-A. Additionally, L-FABP significantly promoted tumor growth and metastasis in a xenograft mouse model. We also assessed the mechanisms of L-FABP activity in tumorigenesis; L-FABP was found to associate with VEGFR2 on membrane rafts and subsequently activate the Akt/mTOR/P70S6K/4EBP1 and Src/FAK/cdc42 pathways, which resulted in up-regulation of VEGF-A accompanied by an increase in both angiogenic potential and migration activity. Our results thus suggest that L-FABP could be a potential target for HCC chemotherapy.

  10. Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

    Science.gov (United States)

    Elmes, Matthew W; Kaczocha, Martin; Berger, William T; Leung, KwanNok; Ralph, Brian P; Wang, Liqun; Sweeney, Joseph M; Miyauchi, Jeremy T; Tsirka, Stella E; Ojima, Iwao; Deutsch, Dale G

    2015-04-03

    Δ(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders.

  11. Molecular characterization, functional expression, tissue localization and protective potential of a Taenia solium fatty acid-binding protein.

    Science.gov (United States)

    Illescas, Oscar; Carrero, Julio C; Bobes, Raúl J; Flisser, Ana; Rosas, Gabriela; Laclette, Juan P

    2012-12-01

    The fatty acid-binding proteins (FABPs) comprise a family of proteins that are widely expressed in animal cells and perform a variety of vital functions. Here, we report the identification, characterization, recombinant expression, tissue localization and protective potential of a Taenia solium FABP (TsFABP1). The TsFABP1 primary structure showed all the conserved residues characteristic of the subfamily iv of the intracellular Lipid-Binding Proteins (iLBPs), including those involved in the binding stabilization of the fatty acid molecule. Through a competitive binding assay we found that TsFABP1 is able to bind at least six different fatty acids with preference toward palmitic and stearic acid, suggesting that TsFABP1 is a member of the iLBP subfamily iv. Immunolocalization assays carried out on larval and adult tissues of four species of taeniids using anti-TsFABP1 hyperimmune sera produced in mice and rabbit, showed intense labeling in the tegument of the spiral canal and in subtegumental cytons of the larvae. These findings suggest that the spiral canal might be a major place for FA uptake in the developing scolex. In contrast, only subtegumental cytons in the adult worms stained positive. We propose that TsFABP1 is involved in the mechanism to mobilize fatty acids between compartments in the extensive syncytial tissue of taeniids. Protection assays carried out in a murine model of cysticercosis showed that subcutaneous immunization with TsFABP1 resulted in about 45% reduction of parasite load against an intraperitoneal challenge with Taenia crassiceps cysts. This reduction in parasite load correlated with the level of cellular and humoral immune responses against TsFABP1, as determined in spleen lymphocyte proliferation and ELISA testing.

  12. Liver fatty acid binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice

    OpenAIRE

    Dharmarajan, Sekhar; Newberry, Elizabeth P.; Montenegro, Grace; Nalbantoglu, ILKe; Davis, Victoria R.; Clanahan, Michael J.; Blanc, Valerie; Xie, Yan; Luo, Jianyang; Fleshman, James W.; Kennedy, Susan; Davidson, Nicholas O.

    2013-01-01

    Evidence suggests a relationship between dietary fat intake, obesity and colorectal cancer, implying a role for fatty acid (FA) metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid binding protein (L-Fabp), a dominant intestinal FA binding protein, regulates intestinal FA trafficking and metabolism and L-Fabp deletion attenuates diet-induced obesity. Here we examined whether changes in intestinal FA metabolism following L-Fabp deletion modify adenoma develo...

  13. Effect of liver fatty acid binding protein on fatty acid movement between liposomes and rat liver microsomes.

    Science.gov (United States)

    McCormack, M; Brecher, P

    1987-01-01

    Although movement of fatty acids between bilayers can occur spontaneously, it has been postulated that intracellular movement is facilitated by a class of proteins named fatty acid binding proteins (FABP). In this study we have incorporated long chain fatty acids into multilamellar liposomes made of phosphatidylcholine, incubated them with rat liver microsomes containing an active acyl-CoA synthetase, and measured formation of acyl-CoA in the absence or presence of FABP purified from rat liver. FABP increased about 2-fold the accumulation of acyl-CoA when liposomes were the fatty acid donor. Using fatty acid incorporated into liposomes made either of egg yolk lecithin or of dipalmitoylphosphatidylcholine, it was found that the temperature dependence of acyl-CoA accumulation in the presence of FABP correlated with both the physical state of phospholipid molecules in the liposomes and the binding of fatty acid to FABP, suggesting that fatty acid must first desorb from the liposomes before FABP can have an effect. An FABP-fatty acid complex incubated with microsomes, in the absence of liposomes, resulted in greater acyl-CoA formation than when liposomes were present, suggesting that desorption of fatty acid from the membrane is rate-limiting in the accumulation of acyl-CoA by this system. Finally, an equilibrium dialysis cell separating liposomes from microsomes on opposite sides of a Nuclepore filter was used to show that liver FABP was required for the movement and activation of fatty acid between the compartments. These studies show that liver FABP interacts with fatty acid that desorbs from phospholipid bilayers, and promotes movement to a membrane-bound enzyme, suggesting that FABP may act intracellularly by increasing net desorption of fatty acid from cell membranes. PMID:3446187

  14. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues.

    Science.gov (United States)

    Shan, Tizhong; Liu, Weiyi; Kuang, Shihuan

    2013-01-01

    Adipose tissues regulate metabolism, reproduction, and life span. The development and growth of adipose tissue are due to increases of both adipocyte cell size and cell number; the latter is mediated by adipocyte progenitors. Various markers have been used to identify either adipocyte progenitors or mature adipocytes. The fatty acid binding protein 4 (FABP4), commonly known as adipocyte protein 2 (aP2), has been extensively used as a marker for differentiated adipocytes. However, whether aP2 is expressed in adipogenic progenitors is controversial. Using Cre/LoxP-based cell lineage tracing in mice, we have identified a population of aP2-expressing progenitors in the stromal vascular fraction (SVF) of both white and brown adipose tissues. The aP2-lineage progenitors reside in the adipose stem cell niche and express adipocyte progenitor markers, including CD34, Sca1, Dlk1, and PDGFRα. When isolated and grown in culture, the aP2-expressing SVF cells proliferate and differentiate into adipocytes upon induction. Conversely, ablation of the aP2 lineage greatly reduces the adipogenic potential of SVF cells. When grafted into wild-type mice, the aP2-lineage progenitors give rise to adipose depots in recipient mice. Therefore, the expression of aP2 is not limited to mature adipocytes, but also marks a pool of undifferentiated progenitors associated with the vasculature of adipose tissues. Our finding adds to the repertoire of adipose progenitor markers and points to a new regulator of adipose plasticity.

  15. Sequence Characterization, Tissue-specific Expression and Polymorphism of the Porcine(Sus scrofa) Liver-type Fatty Acid Binding Protein Gene%猪L-FABP基因的克隆、表达特征及遗传多态性研究

    Institute of Scientific and Technical Information of China (English)

    姜延志; 李学伟; 杨光希

    2006-01-01

    In this study, the full-length cDNA of porcine liver-type fatty acid binding protein gene (L-FABP) was obtained by the rapid amplification of cDNA ends (RACE). The nucleotide sequence and the predicted protein sequence share a high sequence identity with their mammalian counterparts. Semi-quantitative RT-PCR revealed that porcine L-FABP gene is expressed in all twelve tissues studied, but a transcript is more abundant in liver and small intestine than in other tissues. The part genomic DNA of the porcine L-FABP gene was amplified by PCR. The coding region of the pig L-FABP gene is organized in four exons and spans an approximate 2.62 kb genomic region. Comparative sequencing of four pig breeds revealed a C→T single nucleotide polymorphism (SNP) within exon 2. The allele and genotype frequencies differed significantly between indigenous Chinese Zang, Dahe,and Yanan pigs with higher frequencies of allele C and genotype CC and Yorkshire pigs with higher frequencies of allele T and genotype TT (P < 0.01). The association analysis suggested that the C→T polymorphism was associated with intramuscular fat content, indicating that the SNP is a potential molecular marker for intramuscular fat content.%FABPs属于脂结合蛋白超家族成员,是一类分子量较小而对脂肪酸有高亲和力的蛋白质,广泛存在于脊椎动物和非脊椎动物的细胞质中.FABPs担当细胞内脂肪酸的运输任务,它们与脂肪酸结合将其运输到脂肪酸氧化的位置、脂肪酸脂化成甘油三醋或磷脂的位置,或者进入细胞核内发挥其可能的调控功能.因此FABPs对脂类代谢具有重要的调控作用.本研究把L-FABP基因作为影响猪肌内脂肪含量的候选基因.为此,利用cDNA末端快速扩增(RACE)和PCR技术,克隆到猪肝脏型脂肪酸结合蛋白基因(L-FABP)的全长cDNA序列(GenBank登录号:AY960623)和部分基因组序列(GenBank登录号:DQ182323).猪L-FABP基因的cDNA序列全长518 bp,该

  16. Lipid Transport through the Fetoplacental Barrier by the Fatty Acid-Binding Proteins in Pregnant Women with Herpes Virus Infection in the third Trimester

    Directory of Open Access Journals (Sweden)

    Michael T. Lucenko, PhD, ScD

    2012-12-01

    Full Text Available In this study, the transport of the long chain polyunsaturated fatty acids (LCPUFAs from the lacunar blood through the syncytiotrophoblast of the placental villi to the fetal cord blood via a saturable protein-mediated mechanism by the heart-type fatty acid-binding proteins (H-FABPs has been examined. Exacerbation of the herpes simplex viruses (HSV-1 in the third trimester of gestation reduces the delivery of the fatty acid-binding proteins to the syncytiotrophoblast. During exacerbation of the HSV-1 infection, the selective transfer of the LCPUFAs across the syncytiotrophoblast basal plasma membrane into the fetal cord blood was observed. The supply of anti-inflammatory ω-3 PUFAs was reduced; however, the inflow of inflammatory arachidonic acid and other ω-6 PUFAs into the fetal blood was increased.

  17. Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner.

    Science.gov (United States)

    Long, Eric K a; Hellberg, Kristina; Foncea, Rocio; Hertzel, Ann V; Suttles, Jill; Bernlohr, David A

    2013-07-01

    Obesity results in increased macrophage recruitment to adipose tissue that promotes a chronic low-grade inflammatory state linked to increased fatty acid efflux from adipocytes. Activated macrophages produce a variety of pro-inflammatory lipids such as leukotriene C4 (LTC4) and 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE) suggesting the hypothesis that fatty acids may stimulate eicosanoid synthesis. To assess if eicosanoid production increases with obesity, adipose tissue of leptin deficient ob/ob mice was analyzed. In ob/ob mice, LTC4 and 12-HETE levels increased in the visceral (but not subcutaneous) adipose depot while the 5-HETE levels decreased and 15-HETE abundance was unchanged. Since macrophages produce the majority of inflammatory molecules in adipose tissue, treatment of RAW264.7 or primary peritoneal macrophages with free fatty acids led to increased secretion of LTC4 and 5-HETE, but not 12- or 15-HETE. Fatty acid binding proteins (FABPs) facilitate the intracellular trafficking of fatty acids and other hydrophobic ligands and in vitro stabilize the LTC4 precursor leukotriene A4 (LTA4) from non-enzymatic hydrolysis. Consistent with a role for FABPs in LTC4 synthesis, treatment of macrophages with HTS01037, a specific FABP inhibitor, resulted in a marked decrease in both basal and fatty acid-stimulated LTC4 secretion but no change in 5-HETE production or 5-lipoxygenase expression. These results indicate that the products of adipocyte lipolysis may stimulate the 5-lipoxygenase pathway leading to FABP-dependent production of LTC4 and contribute to the insulin resistant state.

  18. Serum liver fatty acid binding protein levels correlate positively with obesity and insulin resistance in Chinese young adults.

    Directory of Open Access Journals (Sweden)

    Juan Shi

    Full Text Available BACKGROUND: Liver fatty acid-binding protein (FABP1 plays an inconclusive role in adiposity. We investigated the association of serum FABP1 levels with obesity and insulin resistance in Chinese young people under 30 years old. METHODOLOGY AND PRINCIPAL FINDINGS: Cross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum FABP1 and biochemical characteristics were measured. Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR and by the insulin sensitivity index (S(i derived from Bergman's minimal model. FABP1 levels in obese subjects were significantly higher than those in normal-weight subjects (p<0.001 and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001. Serum FABP1 levels were significantly correlated with many metabolic-related parameters, with BMI and triglycerides as the independent determinants. FABP1 levels remained an independent risk factor of insulin resistance assessed by binary S(i (OR = 1.868 per SD unit, 95% CI [1.035-3.373], p = 0.038 after adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend <0.001. Multiple regression modeling for the MetS and its components demonstrated that hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels. CONCLUSIONS AND SIGNIFICANCE: Serum FABP1 correlates positively with obesity and insulin resistance in Chinese young adults. Our data supports the fact that FABP1 might be an important mediator participating in fatty acid metabolism and energy balance.

  19. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jun [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Ren, Pingping; Zhang, Lin [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Wang, Xing Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Chen, Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Shen, Ying H., E-mail: hyshen@bcm.edu [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States)

    2010-02-26

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.

  20. Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity.

    Science.gov (United States)

    Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

    2011-03-01

    Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of N(ε)-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of N(ε)-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID.

  1. Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.

    Science.gov (United States)

    Negishi, Kousuke; Noiri, Eisei; Doi, Kent; Maeda-Mamiya, Rui; Sugaya, Takeshi; Portilla, Didier; Fujita, Toshiro

    2009-04-01

    The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP levels increased exponentially even in the lowest dose group as early as 2 hours, whereas blood urea nitrogen (BUN) levels increased at 48 hours. In IR-induced AKI, BUN levels increased only in the 30-minute ischemia group 24 hours after reperfusion; however, urinary L-FABP levels increased more than 100-fold, even in the 5-minute ischemia group after 1 hour. In both AKI models, urinary L-FABP levels showed a better correlation with final histological injury scores and glomerular filtration rates measured by fluorescein isothiocyanate-labeled inulin injection than with levels of BUN and urinary N-acetyl-D-glucosaminidase, especially at earlier time points. Receiver operating characteristic curve analysis demonstrated that urinary L-FABP was superior to other biomarkers for the detection of significant histological injuries and functional declines. In conclusion, urinary L-FABP levels are better suited to allow the accurate and earlier detection of both histological and functional insults in ischemic and nephrotoxin-induced AKI compared with conventional renal markers.

  2. Plasma Free Fatty Acids, Fatty Acid-binding Protein 4, and Mortality in Older Adults (From the Cardiovascular Health Study)

    Science.gov (United States)

    Miedema, Michael D.; Maziarz, Marlena; Biggs, Mary L.; Zieman, Susan J.; Kizer, Jorge R.; Ix, Joachim H.; Mozaffarian, Dariush; Tracy, Russell P.; Psaty, Bruce M.; Siscovick, David S.; Mukamal, Kenneth J.; Djousse, Luc

    2014-01-01

    Plasma free fatty acids (FFA) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992–1993 as part of the Cardiovascular Health Study, an observational cohort of community dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio (HR) per standard deviation (SD): 1.14, 95% confidence interval (CI) 1.09–1.18), but FABP4 levels were not (HR 1.04, 95% CI 0.98–1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death due to cardiovascular disease, dementia, infection, and respiratory causes, but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p=0.45), but FABP4 appeared to be associated with total mortality differentially among men and women (HR 1.17 (1.08–1.26) for men, HR 1.02 (0.96–1.07) for women, interaction p-value <0.001). In conclusion, in a cohort of community-dwelling older individuals, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and non-cardiovascular mortality. PMID:25073566

  3. Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease.

    Directory of Open Access Journals (Sweden)

    Masato Furuhashi

    Full Text Available BACKGROUND: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2, a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD, a group at high risk for atherosclerosis-associated morbidity and mortality. METHODS AND RESULTS: Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD. Serum FABP4 level in females (404.2±30.5 ng/ml was significantly higher than that in males (315.8±30.0 ng/ml, and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05-25.31. CONCLUSION: These findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.

  4. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Mika; Sugiyama, Shigeru, E-mail: sugiyama@chem.eng.osaka-u.ac.jp [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Ishida, Hanako; Niiyama, Mayumi [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Daisuke; Hara, Toshiaki [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Mizohata, Eiichi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Murakami, Satoshi [Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Kanagaw 226-8501 (Japan); Inoue, Tsuyoshi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Shigeru; Murata, Michio [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan)

    2013-11-01

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS.

  5. Upregulation of peroxisome proliferator-activated receptors and liver fatty acid binding protein in hepatic cells of broiler chicken supplemented with conjugated linoleic acids

    Directory of Open Access Journals (Sweden)

    Suriya Kumari Ramiah

    2015-09-01

    Full Text Available Since conjugated linoleic acid (CLA has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR and liver fatty acid binding protein (LFABP in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks were randomly assigned to two diets containing 0 and 2.5% CLA and fed for 6 weeks. Fatty acid (FA composition of liver and PPAR α and γ and L-FABP were analyzed. It has been demonstrated that CLA was found in the liver of CLA-feed chicken compared to control group. Hepatic PPAR α and γ mRNA levels were upregulated 1.2 and 3-fold in CLA-fed chickens compared to chickens fed diet without CLA respectively. A similar response of upregulation was observed for L-FABP mRNA expression. Our data highlights the role of PPARs as a core regulator in the regulation of lipid metabolism in chicken liver.

  6. Sex Differences in Long Chain Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

    Science.gov (United States)

    Ockner, Robert K.; Burnett, David A.; Lysenko, Nina; Manning, Joan A.

    1979-01-01

    Female sex and estrogen administration are associated with increased hepatic production of triglyceride-rich lipoproteins; the basis for this has not been fully elucidated. Inasmuch as hepatic lipoprotein production is also influenced by FFA availability and triglyceride biosynthesis, we investigated sex differences in FFA utilization in rat hepatocyte suspensions and in the components of the triglyceride biosynthetic pathway. Isolated adult rat hepatocyte suspensions were incubated with albumin-bound [14C]oleate for up to 15 min. At physiological and low oleate concentrations, cells from females incorporated significantly more 14C into glycerolipids, especially triglycerides, and into oxidation products than did male cells, per milligram cell protein. At 0.44 mM oleate, incorporation into triglycerides in female cells was approximately twice that in male cells. Comparable sex differences were observed in cells from fasted animals and when [14C]-glycerol incorporation was measured. At higher oleate concentrations, i.e., fatty acid:albumin mole ratios in excess of 2:1, these sex differences were no longer demonstrable, suggesting that maximal rates of fatty acid esterification and oxidation were similar in female and male cells. In female and male hepatic microsomes, specific activities of long chain acyl coenzyme A synthetase, phosphatidate phosphohydrolase, and diglyceride acyltransferase were similar, but glycerol-3-phosphate acyltransferase activity was slightly greater in females at certain substrate concentrations. Microsomal incorporation of [14C]oleate into total glycerolipids was not significantly greater in females. In further contrast to intact cells, microsomal incorporation of [14C]oleate into triglycerides, although significantly greater in female microsomes, accounted for only a small fraction of the fatty acid esterified. The binding affinity and stoichiometry of partially purified female hepatic fatty acid binding protein (FABP) were similar to

  7. Association between codon 54 polymorphism of intestinal fatty acid-binding protein 2 gene and plasma lipids in middle-aged and old populations%中老年人群小肠脂肪酸结合蛋白FABP2基因54位密码子多态性与血脂水平的关系

    Institute of Scientific and Technical Information of China (English)

    常晓彤; 王振辉; 侯丽娟; 李彪英; 董明纲; 李桂喜

    2008-01-01

    背景:有研究表明,在不同人群中,突变型54T FABP2与血脂障碍以及代谢综合征的其他特征相关.目的: 调查中老年人群小肠脂肪酸结合蛋白FABP2基因多态性频率分布,分析突变型54T FABP2基因与血脂水平的关系.设计:病例-对照分析.单位: 河北北方学院生物化学教研室和解放军第二五一医院检验科.对象:选择2003-10/2005-04在解放军第二五一医院体检中心进行体检的中老年人469名,男217名,平均年龄(56±10)岁;女252名,平均年龄(55±13)岁.除外肝、肾功能异常者,相互间无血缘关系;患者均对本实验均知情同意.实验已经医院伦理委员会批准.方法:①空腹12 h后,采用全自动生化仪(Olympus AU 6400)测定血浆总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白AⅠ、载脂蛋白B水平.②采集空腹静脉血1mL,枸橼酸钠抗凝,分离白细胞,蛋白酶K消化,酚/氯仿抽提基因组DNA.采用PCR-限制性片段长度多态性技术检测各组基因型分布频率.主要观察指标:①血脂水平.②FABP2 54位点基因型分布频率.结果:①频率分布:男性54A/T FABP2基因型频率分布为A/A0.48,A/T 0.42,T/T0.10;女性为A/A0.44,A/T0.46,T/T 0.10.男性和女性突变型54T等位基因频率分别为0.31,0.33.男女间频率分布情况比较,差异无显著性意义(P > 0.05).②血脂:男性,54T等位基因携带者血浆低密度脂蛋白胆固醇、载脂蛋白B高于54A等位基因携带者,差异有显著性意义(P < 0.05);女性,54T等位基因携带者血浆总胆固醇、低密度脂蛋白胆固醇高于54A等位基因携带者,差异有显著性意义(P < 0.05).结论:在中老年人群中,FABP2基因多态性频率分布与性别无关;54T FABP2基因携带者有高血脂特征.%BACKGROUND: Studies have shown that alanine (A) to threonine (T) substitution at codon 54 of intestinal fatty acid-binding protein (FABP2) in different populations

  8. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    Directory of Open Access Journals (Sweden)

    Moch Holger

    2009-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP are involved in the intracellular transport of fatty acids (FA. We examined the level of brain-type (B and liver-type (L FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test, correlations and survival analyses. Results B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4 showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2. Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. Conclusion While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients

  9. [Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan].

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Ichikawa, Daisuke; Matsui, Katsuomi; Yokoyama, Takeshi; Sugaya, Takeshi; Kimura, Kenjiro

    2013-07-01

    Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.

  10. Fatty Acid Binding Protein-1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias.

    Science.gov (United States)

    Schroeder, Friedhelm; McIntosh, Avery L; Martin, Gregory G; Huang, Huan; Landrock, Danilo; Chung, Sarah; Landrock, Kerstin K; Dangott, Lawrence J; Li, Shengrong; Kaczocha, Martin; Murphy, Eric J; Atshaves, Barbara P; Kier, Ann B

    2016-06-01

    The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine, and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear-especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human single nucleotide polymorphism (SNP) (26-38 % minor allele frequency and 8.3 ± 1.9 % homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant's impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system in hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.

  11. Influence of Ala54Thr polymorphism of fatty acid-binding protein 2 on histological alterations and insulin resistance of non alcoholic fatty liver disease.

    Science.gov (United States)

    Aller, R; De Luis, D A; Fernandez, L; Calle, F; Velayos, B; Izaola, O; Gonzalez Sagrado, M; Conde, R; Gonzalez, J M

    2009-01-01

    A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the influence of Ala54Thr polymorphism in the FABP2 gene on the histological alterations of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Thirty subjects with the presence of biopsy-proven NAFLD were enrolled for this study. Glucose, Insulin, Insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, resistin, leptin, adiponectin, interleukin-6 and TNF-alfa serum levels were measured at basal time. A tetrapolar bioimpedance, BMI, waist circumference, waist to hip ratio, blood pressure and a prospective serial assessment of nutritional intake with 3 days written food records were examined. Genotype of Ala54Thr FABP2 gene polymorphism was studied. The mean age was 41.6 +/- 11 years and the mean BMI 29.2 +/- 6.6 with 24 males (80%) and 6 females (20%). Fifteen patients (50%) had the genotype Ala54/Ala54 (wild type group) and 15 (50%) patients Ala54/Thr54 (13 patients) or Thr54/Thr54 (2 patients) (mutant type group). Both genotype groups have the similar anthropometric parameters. Serum aspartate aminotransferase and alcaline phosfatase were higher in wild type group than mutant type group, with an unclear explanation. Dietary intake was similar in both groups. A non-statistical significant low levels of adiponectin in mutant group was observed. No differences were detected among other adipokines. There were no differences between genotypes in histological results of inflammation (portal or lobular inflammation) or grade of steatosis or fibrosis. In conclusion, the present study demonstrates that the polymorphism Ala54Thr of FABP in patients with NAFLD doesn't predict liver histological changes, nor both insulin resistance

  12. Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the Women's Health Initiative Observational Study.

    Science.gov (United States)

    Chan, Kei-Hang K; Song, Yiqing; Hsu, Yi-Hsiang; You, Nai-Chieh Y; F Tinker, Lesley; Liu, Simin

    2010-09-01

    Adipocypte fatty acid-binding protein-4 (FABP4/adipocyte P2) may play a central role in energy metabolism and inflammation. In animal models, defects of the aP2 gene (aP2(-/-)) partially protected against the development of obesity-related insulin resistance, dyslipidemia, and atherosclerosis. However, it is unclear whether common genetic variation in FABP4 gene contributes to risk of type 2 diabetes (T2D) or diabetes-related metabolic traits in humans. We comprehensively assess the genetic associations of variants in the FABP4 gene with T2D risk and diabetes-associated biomarkers in a prospective study of 1,529 cases and 2,147 controls among postmenopausal women aged 50-79 years who enrolled in the Women's Health Initiative Observational Study (WHI-OS). We selected and genotyped a total of 11 haplotype-tagging single-nucleotide polymorphisms (tSNPs) spanning 41.3 kb across FABP4 in all samples. None of the SNPs and their derived haplotypes showed significant association with T2D risk. There were no significant associations between SNPs and plasma levels of inflammatory and endothelial biomarkers, including C-reactive protein, tumor necrosis factor (TNF), interleukin-6 (IL-6), E-selectin, and intercellular adhesion molecule (ICAM-1). Among African-American women, several SNPs were significantly associated with lower levels of vascular cell adhesion molecule-1 (VCAM-1), especially among those with incident T2D. On average, plasma levels of VCAM-1 were significantly lower among carriers of each minor allele at rs1486004(C/T; -1.08 ng/ml, P = 0.01), rs7017115(A/G; -1.07 ng/ml, P = 0.02), and rs2290201(C/T; -1.12 ng/ml, P = 0.002) as compared with the homozygotes of the common allele, respectively. After adjusting for multiple testing, carriers of the rs2290201 minor allele remained significantly associated with decreasing levels of plasma VCAM-1 in these women (P = 0.02). In conclusion, our finding from a multiethnic cohort of postmenopausal women did not support the

  13. 肝型脂肪酸结合蛋白研究进展%Advance in Liver-type Fatty Acid Binding Protein

    Institute of Scientific and Technical Information of China (English)

    蔡璨

    2011-01-01

    Liver-type fatty acid binding protein ( L-FABP) is a key member of FABP superfamily, mainly functioning to regulate the absorption and transportation of fatty acid, intracellular transportation of long-chained fatty acid,and redistribution and use of fatty acids in organelles.L-FABP also regulates the target gene transcription mediated by peroxisome proliferator-activated receptor α and impacts on the lipid metabolism and energy balance,as a signalling transduction molecule.L-FABP is closely associated with metabolic diseases and isrhemic injuries of tissues and organs,as a potential sensitive marker of liver,intestinal and renal injuries and target of drug treatment for some metabolic diseases.%肝型脂肪酸结合蛋白(L-FABP)是脂肪酸结合蛋白超家族中的重要成员,主要功能是机体对脂肪酸的吸收、转运及细胞内长链脂肪酸的转运,以及脂肪酸在细胞器内的再分布利用.L-FABP调节过氧化物酶体增殖子激动受体α介导的靶基因转录,影响机体的脂质代谢和能量平衡,起到信号转导分子的作用.L-FABP与代谢性疾病及组织器官缺血损伤等密切相关,有望成为肝、肠、肾等组织损伤的敏感标志物,并可能成为某些代谢性疾病的药物治疗靶点.

  14. Fatty acid-binding proteins and its biological characteristics%脂肪酸结合蛋白及其生物学功能

    Institute of Scientific and Technical Information of China (English)

    陈轶霞; 骆学农; 王红宁

    2012-01-01

    脂肪酸结合蛋白(fatty acid-binding protein,FABP)是胞内脂质结合蛋白超家族成员,存在于脊椎动物和无脊椎动物的细胞内,在长链脂肪酸的摄取、转运及代谢调节中发挥重要作用,并涉及生物体的其他生命过程.本文从FABP的分布、类型、结构、结合及表达特征、生物学功能,特别是近来发现的免疫调节功能等方面阐述了FABP的研究进展,为深入研究该基因家族提供参考.%Fatty acid-binding proteins (FABPs) are members of intracellular lipid binding protein superfamily. These proteins are extensively expressed in animals including invertebrates and vertebrates, and responsible for long chain fatty acid uptake, transport and metabolic regulation and also be involved in many other biological processes. This article reviews research advances in the distribution, type, structure, binding and expression features, immune regulation and the other important biological roles of FABPs. This information presented here will put insights into further studies on FABPs.

  15. Comparison of purified 12 kDa and recombinant 15 kDa Fasciola hepatica antigens related to a Schistosoma mansoni fatty acid binding protein

    Directory of Open Access Journals (Sweden)

    George V. Hillyer

    1995-04-01

    Full Text Available Vaccines in schistosomiasis using homologous antigens have been studied extensively in experimentally infected mammalian hosts. Vaccines using heterologous antigens have received comparatively less attention. This review summarizes recent work on a heterologous 12 kDa Fasciola hepatica antigenic polypeptide which cross reacts with Schistosoma mansoni. A cDNA has been cloned and sequenced, and the predicted amino acid sequence of the recombinant protein has been shown to have significant (44 identity with a 14 kDa S. mansoni fatty acid binding protein. Thus in the parasitic trematodes fatty acid binding proteins may be potential vaccine candidates. The F. hepatica recombinant protein has been overexpressed and purified and denoted rFh15. Preliminary rFh15 migrates more slowly (i.e. may be slightly larger than nFh12 on SDS-PAGE and has a predicted pI of 6.01 vs. observed pI of 5.45. Mice infected with F. hepatica develop antibodies to nFh12 by 2 weeks of infection vs. 6 weeks of infection to rFh15; on the other hand, mice with schistosomiasis mansoni develop antibodies to both nFh12 and rFh15 by 6 weeks of infection. Both the F. hepatica and S. mansoni cross-reactive antigens may be cross-protective antigens with the protection inducing capability against both species.

  16. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake.

    OpenAIRE

    1995-01-01

    To explore the relationship between mitochondrial aspartate aminotransferase (mAspAT; EC 2.6.1.1) and plasma membrane fatty acid-binding protein (FABPpm) and their role in cellular fatty acid uptake, 3T3 fibroblasts were cotransfected with plasmid pMAAT2, containing a full-length mAspAT cDNA downstream of a Zn(2+)-inducible metallothionein promoter, and pFR400, which conveys methotrexate resistance. Transfectants were selected in methotrexate, cloned, and exposed to increasing methotrexate co...

  17. 心肌型脂肪酸结合蛋白的临床应用进展%Clinical Application of Heart Fatty Acid-binding Protein

    Institute of Scientific and Technical Information of China (English)

    范树虹

    2011-01-01

    Heart fatty-acid-binding protein (H-FABP) is a low molecular weight cytostolic protein. It is abundant in the myocardium and has high tissue specificity. Concentration of H-FABP changes regularly in serum after myocardial injury, and is positively correlated with the degree of myocardial injury. H-FABP has been used as an early diagnostic biochemical marker of acute myocardial ischemia. The physio-chemical nature, detection of H-FABP, and its application in the diagnosis of myocardial injury are reviewed in this article.%心肌型脂肪酸结合蛋白(heart fatty acid-binding protein,H-FABP)是一种低分子量可溶性蛋白,在心肌细胞胞浆中含量丰富.具有组织特异性,心肌损伤后血浆中H-FABP水平变化有时间规律性,且血浆H-FABP水平与心肌损伤程度成正相关,故H-FABP可作为诊断早期心肌缺血的生化标志物.现就H-FABP的生理化学特性、检测方法及其在心肌损伤诊断中的应用做一综述.

  18. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Anna Garbelli

    Full Text Available DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication.

  19. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication.

    Science.gov (United States)

    Garbelli, Anna; Beermann, Sandra; Di Cicco, Giulia; Dietrich, Ursula; Maga, Giovanni

    2011-05-12

    DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication.

  20. Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins

    DEFF Research Database (Denmark)

    Madsen, Peder; Rasmussen, H H; Leffers, H

    1992-01-01

    as MRP 14, L1, or calprotectin; calgranulin A or MRP 8; and cystatin A or stefin A. Here, we have cloned and sequenced the cDNA (clone 1592) encoding a new member of this group of low-molecular-weight proteins [isoelectric focusing (IEF) SSP 3007 in the keratinocyte 2D gel protein database] that we have...

  1. Rapid Diagnosis of acute kidney injury (AKI associated with cardiac surgery, using the liver type fatty acid binding protein (L-FABP biomarker

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    Mirbagheri L

    2012-01-01

    Full Text Available Background and objectives: cardiac surgery is often associated with acutekidney injury (AKI. Nowadays, AKI is typically diagnosed by an increase inserum creatinine, which is a delayed and unreliable biomarker. Recent studiesrecommended using the liver type fatty acid binding protein (L-FABP as anearly biomarker.Material and Methods: The urine samples of 18 adult patients undergoingcardiac surgery were collected in different times before (2, 4,8,24 hour andafter cardiac surgery for detection of L-FABP by Elisa.Results: The results from ELISA test show that the increasing amount of LFABPin urine samples of 4 patients is a diagnostic indicator for AKI. Themean concentration of L-FABP has increased up to 17 times at 8 hours aftercardiac surgery compared to before surgery.Conclusion: according to our findings, we speculated that the urinary L-FABPcan be a reliable and rapid biomarker for diagnosis of acute kidney injury.Key words: Acute Kidney Injury, Liver type Fatty Acid Binding Protein,Cardiac surgery

  2. Influence of berberine combining with atorvastatin on serum high-sensitivity C-reactive protein and adipocyte fatty acid-binding protein in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Fei-qi ZHU

    2015-01-01

    Full Text Available Objective To observe the influence of berberine combining with atorvastatin on serum high-sensitivity C-reactive protein (hs-CRP and adipocyte fatty acid-binding protein (A-FABP in patients with acute ischemic stroke.  Methods Ischemic stroke patients (N = 55 were randomized into 3 groups: atorvastatin 20 mg/d (N = 28, atorvastatin 40 mg/d (N = 11 and berberine 0.40 g three times a day + atorvastatin 20 mg/d (combined treatment, N = 16. They were treated for 3 months. The expression changes of serum hs-CRP and A-FABP before and after treatment were compared among 3 groups.  Results There were significant decreases between before and 3 months after treatment on the expression of hs-CRP and A-FABP in 3 groups (P = 0.023, 0.000. After treatment, both the expression of hs-CRP and A-FABP significantly decreased, and the decreases were (1.69 ± 2.29 and (281.43 ± 311.05 mg/L in atorvastatin 20 mg/d group, (7.81 ± 12.48 and (321.59 ± 289.35 mg/L in atorvastatin 40 mg/d group, and (2.16 ± 3.34 and (376.55 ± 249.72 mg/L in combined treatment group. However, there was no significant difference among 3 groups (P > 0.05, for all, and there was no correlation between drugs and observation time points (P > 0.05, for all.  Conclusions The effect of berberine combined with atorvastatin on hs-CRP and A-FABP is similar to atorvastation (40 mg/d therapy. DOI: 10.3969/j.issn.1672-6731.2015.01.010

  3. 肝型脂肪酸结合蛋白研究进展%Progress in liver type fatty acid binding protein

    Institute of Scientific and Technical Information of China (English)

    王南南; 徐力致; 王亚平

    2012-01-01

    Liver fatty acid binding protein (L-FABP) which mainly expresses in liver, intestine and kidney, is an important member of FABP family. It is found that L-FABP is related to the translocation of saturated fatty acid, unsaturated fatty acid, cholesterol, bile acid and so on. Many studies have indicated that L-FABP was involved in fatty liver, cirrhosis and hepatocarcinoma. Moreover, L-FABP can be an appropriate biomarker in predicting the progression of liver injury. Recent researches have demonstrated that u-LFABP might be a new tool in the prediction of diabetic nephropathy in type 1 diabetic patients. Besides, L-FABP levels reflect the severity of diabetic nephropathy accurately in type 2 diabetes. This article aims to review the characteristics, conformation of L-FABP, and its relationship with some diseases.%肝型脂肪酸结合蛋白(liver fatty acid binding protein,L-FABP)是脂肪酸结合蛋白(fatty acid binding proteins,FABPs)家族重要的成员,在肝脏、小肠、肾脏等组织中均有表达.L-FABP在不饱和脂肪酸、饱和脂肪酸、胆固醇、胆汁酸等转运过程中扮演重要角色.目前研究显示L-FABP在脂肪肝、肝硬化以及肝癌发生发展中起到重要作用,并有望作为肝损伤的早期检测指标.此外,新近研究发现尿中L-FABP水平还可以用于预测1型糖尿病患者的临床结局.在2型糖尿病中,尿中L-FABP与糖尿病性肾病的病程有密切关系.主要就L-FABP的特性、结构及其与疾病的关系做一综述.

  4. Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat.

    Science.gov (United States)

    Clements, Peter; Brady, Sally; York, Malcolm; Berridge, Brian; Mikaelian, Igor; Nicklaus, Rosemary; Gandhi, Mitul; Roman, Ian; Stamp, Clare; Davies, Dai; McGill, Paul; Williams, Thomas; Pettit, Syril; Walker, Dana; Turton, John

    2010-08-01

    We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.

  5. Liver fatty acid-binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice.

    Science.gov (United States)

    Dharmarajan, Sekhar; Newberry, Elizabeth P; Montenegro, Grace; Nalbantoglu, Ilke; Davis, Victoria R; Clanahan, Michael J; Blanc, Valerie; Xie, Yan; Luo, Jianyang; Fleshman, James W; Kennedy, Susan; Davidson, Nicholas O

    2013-10-01

    Evidence suggests a relationship between dietary fat intake, obesity, and colorectal cancer, implying a role for fatty acid metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid-binding protein (L-Fabp), a dominant intestinal fatty acid-binding protein, regulates intestinal fatty acid trafficking and metabolism, and L-Fabp deletion attenuates diet-induced obesity. Here, we examined whether changes in intestinal fatty acid metabolism following L-Fabp deletion modify adenoma development in Apc(Min)(/+) mice. Compound L-Fabp(-/-)Apc(Min)(/+) mice were generated and fed a 10% fat diet balanced equally between saturated, monounsaturated, and polyunsaturated fat. L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in adenoma number and total polyp area compared with Apc(Min)(/+)controls, reflecting a significant shift in distribution toward smaller polyps. Adenomas from L-Fabp(-/-)Apc(Min)(/+) mice exhibited reductions in cellular proliferation, high-grade dysplasia, and nuclear β-catenin translocation. Intestinal fatty acid content was increased in L-Fabp(-/-)Apc(Min)(/+) mice, and lipidomic profiling of intestinal mucosa revealed significant shifts to polyunsaturated fatty acid species with reduced saturated fatty acid species. L-Fabp(-/-)Apc(Min)(/+) mice also showed corresponding changes in mRNA expression of enzymes involved in fatty acid elongation and desaturation. Furthermore, adenomas from L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in mRNA abundance of nuclear hormone receptors involved in cellular proliferation and in enzymes involved in lipogenesis. These findings collectively implicate L-Fabp as an important genetic modifier of intestinal tumorigenesis, and identify fatty acid trafficking and metabolic compartmentalization as an important pathway linking dietary fat intake, obesity, and intestinal tumor formation.

  6. Bombyx mori nucleopolyhedrovirus nucleic acid binding proteins BRO-B and BRO-E associate with host T-cell intracellular antigen 1 homologue BmTRN-1 to influence protein synthesis during infection.

    Science.gov (United States)

    Kotani, Eiji; Muto, Sayaka; Ijiri, Hiroshi; Mori, Hajime

    2015-07-01

    Previous reports have indicated that the Bombyx mori nucleopolyhedrovirus (BmNPV) nucleic acid binding proteins BRO-B and BRO-E are expressed during the early stage of infection and that the BRO family likely supports the regulation of mRNA; however, no study has directly examined the function of BRO family proteins in virus-permissive cells. Here, we show that BRO-B and BRO-E associate with cellular T-cell intracellular antigen 1 homologue (BmTRN-1), a translational regulator, and other cellular translation-related proteins in silkworm cells during viral infection. We created BM-N cells that expressed BRO-B/E to study molecular interactions between BmTRN-1 and BRO-B/E and how they influenced protein synthesis. Fluorescent microscopy revealed that BmTRN-1 was localized in cytoplasmic foci during BmNPV infection. Immunofluorescence studies confirmed that BmTRN-1 and BRO-B/E were colocalized in the amorphous conspicuous cytoplasmic foci. Reporter gene studies revealed that co-expression of BRO-B/E synergistically led to a significant decrease in protein synthesis from a designed transcript carrying the 5'untranslated region of a cellular mRNA with no significant change of transcript abundance. Additionally, RNA interference-mediated knockdown of BmTRN-1 resulted in a marked inhibition of the ability of BRO-B/E to regulate the transcript. These results suggested that the association of BmTRN-1 with BRO-B/E is responsible for the inhibitory regulation of certain mRNAs at the post-transcriptional level and add an additional mechanism for how baculoviruses control protein synthesis during infection.

  7. Structural and functional interaction of fatty acids with human liver fatty acid-binding protein (L-FABP) T94A variant.

    Science.gov (United States)

    Huang, Huan; McIntosh, Avery L; Martin, Gregory G; Landrock, Kerstin K; Landrock, Danilo; Gupta, Shipra; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2014-05-01

    The human liver fatty acid-binding protein (L-FABP) T94A variant, the most common in the FABP family, has been associated with elevated liver triglyceride levels. How this amino acid substitution elicits these effects is not known. This issue was addressed using human recombinant wild-type (WT) and T94A variant L-FABP proteins as well as cultured primary human hepatocytes expressing the respective proteins (genotyped as TT, TC and CC). The T94A substitution did not alter or only slightly altered L-FABP binding affinities for saturated, monounsaturated or polyunsaturated long chain fatty acids, nor did it change the affinity for intermediates of triglyceride synthesis. Nevertheless, the T94A substitution markedly altered the secondary structural response of L-FABP induced by binding long chain fatty acids or intermediates of triglyceride synthesis. Finally, the T94A substitution markedly decreased the levels of induction of peroxisome proliferator-activated receptor α-regulated proteins such as L-FABP, fatty acid transport protein 5 and peroxisome proliferator-activated receptor α itself meditated by the polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid in cultured primary human hepatocytes. Thus, although the T94A substitution did not alter the affinity of human L-FABP for long chain fatty acids, it significantly altered human L-FABP structure and stability, as well as the conformational and functional response to these ligands.

  8. A new size-independent score for pairwise protein structure alignment and its application to structure classification and nucleic-acid binding prediction.

    Science.gov (United States)

    Yang, Yuedong; Zhan, Jian; Zhao, Huiying; Zhou, Yaoqi

    2012-08-01

    A structure alignment program aligns two structures by optimizing a scoring function that measures structural similarity. It is highly desirable that such scoring function is independent of the sizes of proteins in comparison so that the significance of alignment across different sizes of the protein regions aligned is comparable. Here, we developed a new score called SP-score that fixes the cutoff distance at 4 Å and removed the size dependence using a normalization prefactor. We further built a program called SPalign that optimizes SP-score for structure alignment. SPalign was applied to recognize proteins within the same structure fold and having the same function of DNA or RNA binding. For fold discrimination, SPalign improves sensitivity over TMalign for the chain-level comparison by 12% and over DALI for the domain-level comparison by 13% at the same specificity of 99.6%. The difference between TMalign and SPalign at the chain level is due to the inability of TMalign to detect single domain similarity between multidomain proteins. For recognizing nucleic acid binding proteins, SPalign consistently improves over TMalign by 12% and DALI by 31% in average value of Mathews correlation coefficients for four datasets. SPalign with default setting is 14% faster than TMalign. SPalign is expected to be useful for function prediction and comparing structures with or without domains defined. The source code for SPalign and the server are available at http://sparks.informatics.iupui.edu.

  9. Conserved charged amino acids are key determinants for fatty acid binding proteins (FABPs)-membrane interactions. A multi-methodological computational approach.

    Science.gov (United States)

    Zamarreño, Fernando; Giorgetti, Alejandro; Amundarain, María Julia; Viso, Juan Francisco; Córsico, Betina; Costabel, Marcelo D

    2017-03-16

    Based on the analysis of the mechanism of ligand transfer to membranes employing in vitro methods, Fatty Acid Binding Protein (FABP) family has been divided in two subgroups: collisional and diffusional FABPs. Although the collisional mechanism has been well characterized employing in vitro methods, the structural features responsible for the difference between collisional and diffusional mechanisms remain uncertain. In this work, we have identified the amino acids putatively responsible for the interaction with membranes of both, collisional and diffusional, subgroups of FABPs. Moreover, we show how specific changes in FABPs' structure could change the mechanism of interaction with membranes. We have computed protein-membrane interaction energies for members of each subgroup of the family, and performed Molecular Dynamics simulations that have shown different configurations for the initial interaction between FABPs and membranes. In order to generalize our hypothesis, we extended the electrostatic and bioinformatics analysis over FABPs of different mammalian genus. Also, our methodological approach could be used for other systems involving protein-membrane interactions.

  10. TGD4 involved in endoplasmic reticulum-to-chloroplast lipid trafficking is a phosphatidic acid binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Wang Z.; Xu C.; Benning, C.

    2012-05-01

    The synthesis of galactoglycerolipids, which are prevalent in photosynthetic membranes, involves enzymes at the endoplasmic reticulum (ER) and the chloroplast envelope membranes. Genetic analysis of trigalactosyldiacylglycerol (TGD) proteins in Arabidopsis has demonstrated their role in polar lipid transfer from the ER to the chloroplast. The TGD1, 2, and 3 proteins resemble components of a bacterial-type ATP-binding cassette (ABC) transporter, with TGD1 representing the permease, TGD2 the substrate binding protein, and TGD3 the ATPase. However, the function of the TGD4 protein in this process is less clear and its location in plant cells remains to be firmly determined. The predicted C-terminal {beta}-barrel structure of TGD4 is weakly similar to proteins of the outer cell membrane of Gram-negative bacteria. Here, we show that, like TGD2, the TGD4 protein when fused to DsRED specifically binds phosphatidic acid (PtdOH). As previously shown for tgd1 mutants, tgd4 mutants have elevated PtdOH content, probably in extraplastidic membranes. Using highly purified and specific antibodies to probe different cell fractions, we demonstrated that the TGD4 protein was present in the outer envelope membrane of chloroplasts, where it appeared to be deeply buried within the membrane except for the N-terminus, which was found to be exposed to the cytosol. It is proposed that TGD4 is either directly involved in the transfer of polar lipids, possibly PtdOH, from the ER to the outer chloroplast envelope membrane or in the transfer of PtdOH through the outer envelope membrane.

  11. The Trypanosoma cruzi nucleic acid binding protein Tc38 presents changes in the intramitochondrial distribution during the cell cycle

    Directory of Open Access Journals (Sweden)

    Nardelli Sheila C

    2009-02-01

    Full Text Available Abstract Background Tc38 of Trypanosoma cruzi has been isolated as a single stranded DNA binding protein with high specificity for the poly [dT-dG] sequence. It is present only in Kinetoplastidae protozoa and its sequence lacks homology to known functional domains. Tc38 orthologues present in Trypanosoma brucei and Leishmania were proposed to participate in quite different cellular processes. To further understand the function of this protein in Trypanosoma cruzi, we examined its in vitro binding to biologically relevant [dT-dG] enriched sequences, its expression and subcellular localization during the cell cycle and through the parasite life stages. Results By using specific antibodies, we found that Tc38 protein from epimastigote extracts participates in complexes with the poly [dT-dG] probe as well as with the universal minicircle sequence (UMS, a related repeated sequence found in maxicircle DNA, and the telomeric repeat. However, we found that Tc38 predominantly localizes into the mitochondrion. Though Tc38 is constitutively expressed through non-replicating and replicating life stages of T. cruzi, its subcellular localization in the unique parasite mitochondrion changes according to the cell cycle stage. In epimastigotes, Tc38 is found only in association with kDNA in G1 phase. From the S to G2 phase the protein localizes in two defined and connected spots flanking the kDNA. These spots disappear in late G2 turning into a diffuse dotted signal which extends beyond the kinetoplast. This later pattern is more evident in mitosis and cytokinesis. Finally, late in cytokinesis Tc38 reacquires its association with the kinetoplast. In non-replicating parasite stages such as trypomastigotes, the protein is found only surrounding the entire kinetoplast structure. Conclusions The dynamics of Tc38 subcellular localization observed during the cell cycle and life stages support a major role for Tc38 related to kDNA replication and maintenance.

  12. Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1∙Nup98)

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Beili; Seo, Hyuk-Soo; Blobel, Günter; Ren, Yi [Rockefeller

    2014-07-01

    mRNA export factor 1 (Rae1) and nucleoporin 98 (Nup98) are host cell targets for the matrix (M) protein of vesicular stomatitis virus (VSV). How Rae1 functions in mRNA export and how M protein targets both Rae1 and Nup98 are not understood at the molecular level. To obtain structural insights, we assembled a 1:1:1 complex of M•Rae1•Nup98 and established a crystal structure at 3.15-Å resolution. We found that the M protein contacts the Rae1•Nup98 heterodimer principally by two protrusions projecting from the globular domain of M like a finger and thumb. Both projections clamp to the side of the β-propeller of Rae1, with the finger also contacting Nup98. The most prominent feature of the finger is highly conserved Methionine 51 (Met51) with upstream and downstream acidic residues. The complementary surface on Rae1 displays a deep hydrophobic pocket, into which Met51 fastens like a bolt, and a groove of basic residues on either side, which bond to the acidic residues of the finger. Notably, the M protein competed for in vitro binding of various oligonucleotides to Rae1•Nup98. We localized this competing activity of M to its finger using a synthetic peptide. Collectively, our data suggest that Rae1 serves as a binding protein for the phosphate backbone of any nucleic acid and that the finger of M mimics this ligand. In the context of mRNA export, we propose that a given mRNA segment, after having been deproteinated by helicase, is transiently reproteinated by Nup98-tethered Rae1. We suggest that such repetitive cycles provide cytoplasmic stopover sites required for ratcheting mRNA across the nuclear pore.

  13. Effects of linoleic and gamma-linolenic acids (efamol evening primrose oil) on fatty acid-binding proteins of rat liver.

    Science.gov (United States)

    Dutta-Roy, A K; Demarco, A C; Raha, S K; Shay, J; Garvey, M; Horrobin, D F

    We have studied the effects of Efamol evening primrose oil (EPO) on fatty acid-binding proteins (L-FABP) of rat liver. EPO contains 72% cis-linoleic acid and 9% cis-gamma linolenic acid. EPO has been clinically used for treatment of a number of diseases in humans and animals. EPO is also known to lower cholesterol level in humans and animals. Feeding of an EPO supplemented diet to rats (n = 9) for 2 months decreases the oleate binding capacity of purified L-FABP of rat liver whereas the palmitate binding activity was increased by 38%. However, EPO feeding did not alter the L-FABP concentrations significantly as measured by using the fluorescence fatty acid probe, dansylamino undecanoic acid. Endogenous fatty acid analysis of L-FABPs revealed significant qualitative and quantitative changes in fatty acid pattern after EPO feeding. EPO feeding decreased the endogenous palmitate level by 53% and oleate level by 64% in L-FABPs and also EPO feeding decreased the total endogenous fatty acid content from 62 nanomole per mg of protein to 42 nanomole per mg of L-FABP (n = 3).

  14. Adipocyte Fatty Acid Binding Protein Potentiates Toxic Lipids-Induced Endoplasmic Reticulum Stress in Macrophages via Inhibition of Janus Kinase 2-dependent Autophagy

    Science.gov (United States)

    Hoo, Ruby L. C.; Shu, Lingling; Cheng, Kenneth K. Y.; Wu, Xiaoping; Liao, Boya; Wu, Donghai; Zhou, Zhiguang; Xu, Aimin

    2017-01-01

    Lipotoxicity is implicated in the pathogenesis of obesity-related inflammatory complications by promoting macrophage infiltration and activation. Endoplasmic reticulum (ER) stress and adipocyte fatty acid binding protein (A-FABP) play key roles in obesity and mediate inflammatory activity through similar signaling pathways. However, little is known about their interplay in lipid-induced inflammatory responses. Here, we showed that prolonged treatment of palmitic acid (PA) increased ER stress and expression of A-FABP, which was accompanied by reduced autophagic flux in macrophages. Over-expression of A-FABP impaired PA-induced autophagy associating with enhanced ER stress and pro-inflammatory cytokine production, while genetic ablation or pharmacological inhibition of A-FABP reversed the conditions. PA-induced expression of autophagy-related protein (Atg)7 was attenuated in A-FABP over-expressed macrophages, but was elevated in A-FABP-deficient macrophages. Mechanistically, A-FABP potentiated the effects of PA by inhibition of Janus Kinase (JAK)2 activity, thus diminished PA-induced Atg7 expression contributing to impaired autophagy and further augmentation of ER stress. These findings suggest that A-FABP acts as autophagy inhibitor to instigate toxic lipids-induced ER stress through inhibition of JAK2-dependent autophagy, which in turn triggers inflammatory responses in macrophages. A-FABP-JAK2 axis may represent an important pathological pathway contributing to obesity-related inflammatory diseases. PMID:28094778

  15. Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

    Science.gov (United States)

    Asada, Toshifumi; Isshiki, Rei; Hayase, Naoki; Sumida, Maki; Inokuchi, Ryota; Noiri, Eisei; Nangaku, Masaomi; Yahagi, Naoki; Doi, Kent

    2016-01-01

    Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793-0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741-0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697-0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

  16. Induction of fatty acid-binding protein 3 in brown adipose tissue correlates with increased demand for adaptive thermogenesis in rodents.

    Science.gov (United States)

    Yamashita, Hitoshi; Wang, Zuocheng; Wang, Youxue; Segawa, Masahiko; Kusudo, Tatsuya; Kontani, Yasuhide

    2008-12-12

    We investigated the contribution of fatty acid-binding protein 3 (FABP3) to adaptive thermogenesis in brown adipose tissue (BAT) in rodents. The expression of FABP3 mRNA in BAT was regulated discriminatively in response to alteration of the ambient temperature, which regulation was similar and reciprocal to the regulation of uncoupling protein 1 (UCP1) and leptin, respectively. FABP3 expression in the BAT was significantly higher in the UCP1-knockout (KO) mice than in the wild-type ones, and these KO mice showed a higher clearance rate of free fatty acid from the plasma. In addition, FABP3 expression in the BAT was increased greatly with the development of diet-induced obesity in mice. These results indicate that the induction of FABP3 in BAT correlates with an increased demand for adaptive thermogenesis in rodents. FABP3 appears to be essential for accelerating fatty acid flux and its oxidation through UCP1 activity for non-shivering thermogenesis in BAT.

  17. HUMAN LIVER FATTY ACID BINDING PROTEIN (L-FABP) T94A VARIANT ALTERS STRUCTURE, STABILITY, AND INTERACTION WITH FIBRATES

    OpenAIRE

    Martin, Gregory G.; McIntosh, Avery L.; Huang, Huan; Gupta, Shipra; Atshaves, Barbara P.; Landrock, Kerstin K.; Landrock, Danilo; Kier, Ann B.; Schroeder, Friedhelm

    2013-01-01

    Although the human L-FABP T94A variant arises from the most commonly occurring SNP in the entire FABP family, there is a complete lack of understanding regarding the role of this polymorphism in human disease. It has been hypothesized that the T94A substitution results in complete loss of ligand binding ability and function analogous to L-FABP gene ablation. This possibility was addressed using recombinant human WT T94T and T94A variant L-FABP and cultured primary human hepatocytes. Non-conse...

  18. Nuclear Magnetic Resonance Structure of the Nucleic Acid-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 3▿

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A.; Chatterjee, Amarnath; Neuman, Benjamin W.; Joseph, Jeremiah S.; Buchmeier, Michael J.; Kuhn, Peter; Wüthrich, Kurt

    2009-01-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand β-sheet holding two α-helices of three and four turns that are oriented antiparallel to the β-strands. Two antiparallel two-strand β-sheets and two 310-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold. PMID:19828617

  19. Loss of sialic acid binding domain redirects protein σ1 to enhance M cell-directed vaccination.

    Directory of Open Access Journals (Sweden)

    Dagmara Zlotkowska

    Full Text Available Ovalbumin (OVA genetically fused to protein sigma 1 (pσ1 results in tolerance to both OVA and pσ1. Pσ1 binds in a multi-step fashion, involving both protein- and carbohydrate-based receptors. To assess the relative pσ1 components responsible for inducing tolerance and the importance of its sialic binding domain (SABD for immunization, modified OVA-pσ1, termed OVA-pσ1(short, was deleted of its SABD, but with its M cell targeting moiety intact, and was found to be immunostimulatory and enhanced CD4(+ and CD8(+ T cell proliferation. When used to nasally immunize mice given with and without cholera toxin (CT adjuvant, elevated SIgA and serum IgG responses were induced, and OVA-pσ1(s was more efficient for immunization than native OVA+CT. The immune antibodies (Abs were derived from elevated Ab-forming cells in the upper respiratory tissues and submaxillary glands and were supported by mixed Th cell responses. Thus, these studies show that pσ1(s can be fused to vaccines to effectively elicit improved SIgA responses.

  20. Polymorphism of human intestinal fatty acid binding protein gene and serum lipid levels in coronary heart disease%小肠脂肪酸结合蛋白基因多态性与冠心病患者血脂水平关系的研究

    Institute of Scientific and Technical Information of China (English)

    邹艳慧; 高学文; 王萍; 云雅丽

    2012-01-01

    explore the relationship between FABP2 54 gene polymorphism and serum lipid levels in different ethnic patients with coronary heart disease.Methods We collected fasting blood from participants,then extracted DNA from whole blood,and detected lipids from serum.We performed 54A/T FABP2 genotyping for participants in the case and the control groups by polymerase chain reaction (PCR) and DNA restriction enzyme digestion techniques.Results ( 1 ) In Hans population with coronary heart disease,the allelic frequency of point in 54T gene was 0.542,and 54A gene was 0.458 ; in urban Mongolian with coronary heart disease,the allelic frequency of point in 54T gene was 0.708,and that of 54A gene was 0.292.The allelic frequency of point in 54T and 54A genes were 0.284 and 0.716 respectively in the Han population control group and 0.353 and 0.647 respectively in the normal urban Mongolian group.Compared with the control groups,mutant 54T allele frequency in the case groups of Han and urban Mongolian was significantly higher ( Han:x2 =14.967,P < 0.05 ; Mongolian:x2 =28.083,P < 0.05 ).Compared with the Han Chinese population with coronary heart disease,the mutant 54T allele frequency in urban Mongolian with coronary heart disease was significantly (x2 =7.111,P < 0.05 ).There was no significant difference in mutant 54T allele frequency between the Mongolian control group and the Han control group ( x2 =3.392,P > 0.05 ).( 2 ) Patients with coronary heart disease who carry Thr54 ( + ) had a significantly higher level of fasting plasma TG [ CC Thr54 (-):( 1.89 ± 0.57 ) mmol/L,CC Thr54 ( + ):( 3.92 ± 1.63 ) mmol/L; CM Thr54 (-):(2.23 ± 0.13 ) mmol/L,CM Thr54 ( + ):(4.03 ± 1.14) mmol/L; Hans:P =0.001,Mongolian:P =0.035 ],and LDL-C [ CC Thr54 (-):( 3.09 ± 0.92) mmol/L,CC Thr54 ( + ):(4.05 ± 1.14 ) mmol/L ; CM Thr54 (-):( 4.26 ± 0.08 ) mmol/L,CM Thr54 ( + ):( 5.10 ± 0.56 ) mmol/L; Hans:P =0.025,Mongolian:P =0.045 ] than those with Thr54 (-).Conclusion (1) Threre is FABP2 gene

  1. Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin.

    Science.gov (United States)

    Lee, Chang Woo; Kim, Jung Eun; Do, Hackwon; Kim, Ryeo-Ok; Lee, Sung Gu; Park, Hyun Ho; Chang, Jeong Ho; Yim, Joung Han; Park, Hyun; Kim, Il-Chan; Lee, Jun Hyuck

    2015-09-11

    Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions.

  2. Distinct roles of urinary liver-type fatty acid-binding protein in non-diabetic patients with anemia.

    Directory of Open Access Journals (Sweden)

    Naohiko Imai

    Full Text Available Various stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients.A total of 156 patients were studied in this retrospective cross-sectional analysis. The associations between anemia and urinary L-FABP levels, and the predictors of urinary L-FABP levels in non-diabetic patients were evaluated.Urinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001 and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001 were significant predictors of urinary L-FABP levels.Urinary L-FABP is strongly associated with anemia in non-diabetic patients.

  3. Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5.

    Science.gov (United States)

    Levi, Liraz; Wang, Zeneng; Doud, Mary Kathryn; Hazen, Stanley L; Noy, Noa

    2015-11-23

    Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes and precursors for signalling molecules. Here we show that these biological compounds also regulate gene expression and that they do so by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. The data indicate that these activities of LCFA are mediated by FABP5, which delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. We show further that, by concomitantly promoting the activation of RAR and inhibiting the activation of PPARβ/δ, SLCFA suppress the oncogenic properties of FABP5-expressing carcinoma cells in cultured cells and in vivo. The observations suggest that compounds that inhibit FABP5 may constitute a new class of drugs for therapy of certain types of cancer.

  4. Research Progress in Intestinal-type Fatty Acid Binding Protein%肠型脂肪酸结合蛋白研究进展

    Institute of Scientific and Technical Information of China (English)

    王家胜; 杨强

    2012-01-01

    肠型脂肪酸结合蛋白( Ⅰ-FABP,FABP2)是脂肪酸结合蛋白超家族中的重要成员,主要参与机体对脂肪酸的吸收、转运、以及在细胞器内的再分布及利用.近年研究表明,FABP2与代谢性疾病、炎症性疾病、肠组织缺血损伤等密切相关,不但是肠组织损伤的敏感性标志,而且可以作为炎症严重程度的评价指标,并可能成为某些代谢性疾病的药物治疗靶点.%Intestinal-type fatty acid binding protein (I-FABP, FABP2 ) is a key member of the FABP super family, participating in the organism's absorption,transferring,intracellular redistribution and use of fatty acids. Recent research has demonstrated that FABP2 is closely related with metabolic diseases,inflammatory diseases and ischemic injuries of intestinal tissue. It is not only a sensitive sign of intestinal injuries but also a severity evaluation indicator of inflammation. What's more,it can probably be a pharmacotherapy target of some metabolic diseases.

  5. High sensitive troponin T and heart fatty acid binding protein: Novel biomarker in heart failure with normal ejection fraction?: A cross-sectional study

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    Barroso Michael

    2011-07-01

    Full Text Available Abstract Background High sensitive troponin T (hsTnT and heart fatty acid binding protein (hFABP are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF. We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF. Methods We analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD, and 30 controls with normal diastolic function. Patients were classified to have HFnEF when the diagnostic criteria as recommended by the European Society of Cardiology were met. Results Levels of hs TnT and hFABP were significantly higher in patients with asymptomatic LVDD and HFnEF (both p Conclusion In HFnEF patients, hsTnT and hFABP are elevated independent of coronary artery disease, suggesting that ongoing myocardial damage plays a critical role in the pathophysiology. A combination of biomarkers and echocardiographic parameters might improve diagnostic accuracy and risk stratification of patients with HFnEF.

  6. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats.

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    Elsherbiny, Marwa E; Goruk, Susan; Monckton, Elizabeth A; Richard, Caroline; Brun, Miranda; Emara, Marwan; Field, Catherine J; Godbout, Roseline

    2015-10-22

    Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.

  7. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

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    Marwa E. Elsherbiny

    2015-10-01

    Full Text Available Arachidonic (AA and docosahexaenoic acid (DHA brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7, a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.

  8. Increase in skin autofluorescence and release of heart-type fatty acid binding protein in plasma predicts mortality of hemodialysis patients.

    Science.gov (United States)

    Arsov, Stefan; Trajceska, Lada; van Oeveren, Wim; Smit, Andries J; Dzekova, Pavlina; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Graaff, Reindert

    2013-07-01

    Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (ΔAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty-nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (hs-CRP), heart-type fatty acid binding protein (H-FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1-year ΔAF of HD patients was 0.16 ± 0.06, which was around seven- to ninefold higher than 1-year ΔAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1-year ΔAF, hs-CRP, ICAM-1, and H-FABP were independent predictors of overall mortality. Hypertension, 1-year ΔAF, hs-CRP, and H-FABP were also independent predictors of cardiovascular mortality. One-year ΔAF and plasma H-FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.

  9. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

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    Zulezwan A. Malik

    2013-12-01

    Full Text Available Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC coupled to mass spectrometry (MS affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group bred as either high- or low-capacity runners (HCR and LCR, respectively that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p < 0.0001 in running capacity during a standardized treadmill test. Soluble muscle proteins were extracted, digested with trypsin and individual biological replicates (50 ng of tryptic peptides subjected to LC-MS profiling. Proteins were identified by triplicate LC-MS/MS analysis of a pooled sample of each biological replicate. Differential expression profiling was performed on relative abundances (RA of parent ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897 and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5. Sixteen proteins were significantly (p < 0.05 more abundant in HCR muscle and hierarchal clustering of the profiling data highlighted two protein subgroups, which encompassed proteins associated with either the respiratory chain or fatty acid oxidation. Heart-type fatty acid binding protein (FABPH was 1

  10. Adipocyte fatty acid-binding protein and metabolic syndrome%脂肪细胞型脂肪酸结合蛋白与代谢综合征

    Institute of Scientific and Technical Information of China (English)

    李秋桂; 肖永康; 蒋建华

    2009-01-01

    脂肪细胞型脂肪酸结合蛋白(A-FABP)是近年来新发现的脂肪因子.动物实验表明其可以促进代谢综合征各组分如胰岛素抵抗、血脂紊乱、2型糖尿病和动脉粥样硬化的发生、发展.人群研究也发现,其过度表达而导致血浆中含量增加是反映代谢综合征的一个可靠生物标志物.随着研究的深入,A-FABP对于治疗代谢综合征的作用也日益受到人们的关注.以下主要就近年来有关A-FABP的分布、结构、特性及其与代谢综合征组分的关系作一综述.%Adipocyte fatty acid-binding protein(A-FABP) is a new-found adipocytokine which secreted from adipocyte. Animal experiment indicated that A-FABP can promote the development of insulin resistance, dyslipidemia, type 2 diabetes mellitns and artheroaclerosis in metabolic syndrome. Population studies found that serum A-FABP level might be an independent biomarker of metabolic syndrome. The effect of A-FABP in treating metabolic syndrome is concerned by people gradually. This article introduces the distribution, structure, property of A-FABP, and the relationship between A-FABP and the components of metabolic syndrome.

  11. Role of Heart-Type Fatty Acid Binding Protein in Early Detection of Acute Myocardial Infarction in Comparison with cTnI, CK-MB and Myoglobin

    Institute of Scientific and Technical Information of China (English)

    陈莉莉; 郭小梅; 杨霏

    2004-01-01

    Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB)and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n= 32) and non-AMI group (n= 61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29 % within 3 h and 84.38 %within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100 % within 3h and 91.8 % within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CKMB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris.In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.

  12. Plasma-free fatty acids, fatty acid-binding protein 4, and mortality in older adults (from the Cardiovascular Health Study).

    Science.gov (United States)

    Miedema, Michael D; Maziarz, Marlena; Biggs, Mary L; Zieman, Susan J; Kizer, Jorge R; Ix, Joachim H; Mozaffarian, Dariush; Tracy, Russell P; Psaty, Bruce M; Siscovick, David S; Mukamal, Kenneth J; Djousse, Luc

    2014-09-15

    Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes, but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992 to 1993 as part of the Cardiovascular Health Study, an observational cohort of community-dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio [HR] per SD: 1.14, 95% confidence interval [CI] 1.09 to 1.18), but FABP4 levels were not (HR 1.04, 95% CI 0.98 to 1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death because of cardiovascular disease, dementia, infection, and respiratory causes but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p = 0.45), but FABP4 appeared to be associated with total mortality differentially in men and women (HR 1.17, 95% CI 1.08 to 1.26 for men; HR 1.02, 95% CI 0.96 to 1.07 for women, interaction p value <0.001). In conclusion, in a cohort of community-dwelling older subjects, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and noncardiovascular mortality.

  13. Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

    Institute of Scientific and Technical Information of China (English)

    Yoon Shin Park; Yoosik Yoon; Hong Seok Ahn

    2007-01-01

    AIM: To investigate the effect of Platycodon grandiflorum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats.METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis.RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE significantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue.CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat diet.From these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.

  14. Low Abdominal NIRS Values and Elevated Plasma Intestinal Fatty Acid-Binding Protein in a Premature Piglet Model of Necrotizing Enterocolitis.

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    Irving J Zamora

    Full Text Available To identify early markers of necrotizing enterocolitis (NEC, we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP measured every 6 hours can detect NEC prior to onset of clinical symptoms. Premature piglets received parenteral nutrition for 48-hours after delivery, followed by enteral feeds every three hours until death or euthanasia at 96-hours. Continuous A-NIRS, systemic oxygen saturation (SpO2, and heart rate were measured while monitoring for clinical signs of NEC. Blood samples obtained at 6-hour intervals were used to determine pI-FABP levels by ELISA. Piglets were classified as fulminant-NEC (f-NEC, non-fulminant-NEC (nf-NEC and No-NEC according to severity of clinical and histologic features. Of 38 piglets, 37% (n=14 developed nf-NEC, 18% (n=7 developed f-NEC and 45% (n=17 had No-NEC. There were significant differences in baseline heart rate (p=0.008, SpO2 (p0.25ng/mL identified animals with NEC (68% sensitivity and 90% specificity. NIRS is a real-time, non-invasive tool that can serve as a diagnostic modality for NEC. In premature piglets, low A-NIRS in the early neonatal period and increased variability during initial feeds are highly predictive of NEC, which is then confirmed by rising plasma I-FABP levels. These modalities may help identify neonates with NEC prior to clinical manifestations of disease.

  15. Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME: Background and design of a diagnostic study in primary care

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    Doevendans Pieter A

    2008-04-01

    Full Text Available Abstract Background Currently used biomarkers for cardiac ischemia are elevated in blood plasma after a delay of several hours and therefore unable to detect acute coronary syndrome (ACS in a very early stage. General practitioners (GPs, however, are often confronted with patients suspected of ACS within hours after onset of complaints. This ongoing study aims to evaluate the added diagnostic value beyond clinical assessment for a rapid bedside test for heart-type fatty-acid binding protein (H-FABP, a biomarker that is detectable as soon as one hour after onset of ischemia. Methods Participating GPs perform a blinded H-FABP rapid bedside test (Cardiodetect® in patients with symptoms suggestive of ACS such as chest pain or discomfort at rest. All patients, whether referred to hospital or not, undergo electrocardiography (ECG and venapunction for a plasma troponin test within 12–36 hours after onset of complaints. A final diagnosis will be established by an expert panel consisting of two cardiologists and one general practitioner (blinded to the H-FABP test result, using all available patient information, also including signs and symptoms. The added diagnostic value of the H-FABP test beyond history taking and physical examination will be determined with receiver operating characteristic curves derived from multivariate regression analysis. Conclusion Reasons for presenting the design of our study include the prevention of publication bias and unacknowledged alterations in the study aim, design or data-analysis. To our knowledge this study is the first to assess the diagnostic value of H-FABP outside a hospital-setting. Several previous hospital-based studies showed the potential value of H-FABP in diagnosing ACS. Up to now however it is unclear whether these results are equally promising when the test is used in primary care. The first results are expected in the end of 2008.

  16. Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity.

    Science.gov (United States)

    Kano, Fumiya; Matsubara, Kohki; Ueda, Minoru; Hibi, Hideharu; Yamamoto, Akihito

    2017-03-01

    Peripheral nerves (PNs) exhibit remarkable self-repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, we show that an implantation of the serum-free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED-CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. In contrast, SHED-CM specifically depleted of a set of anti-inflammatory M2 macrophage inducers, monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9) lost the ability to restore neurological function in this model. Notably, the combination of MCP-1 and sSiglec-9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, the implantation of a collagen graft containing MCP-1/sSiglec-9 into the nerve gap induced anti-inflammatory M2 macrophage polarization, generated a Schwann-cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. The specific elimination of M2 macrophages by Mannosylated-Clodrosome suppressed the MCP-1/sSiglec-9-mediated neurological recovery. Taken together, our data suggest that MCP-1/sSiglec-9 regenerates PNs by inducing tissue-repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries. Stem Cells 2017;35:641-653.

  17. Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.

    Science.gov (United States)

    Martin, Ivelisse; Cabán-Hernández, Kimberly; Figueroa-Santiago, Olgary; Espino, Ana M

    2015-04-15

    TLR4, the innate immunity receptor for bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. There is a need to develop molecules that block either activation through TLR4 or the downstream signaling pathways to inhibit the storm of inflammation typically elicited by bacterial LPS, which is a major cause of the high mortality associated with bacterial sepsis. We report in this article that a single i.p. injection of 15 μg fatty acid binding protein from Fasciola hepatica (Fh12) 1 h before exposure to LPS suppressed significantly the expression of serum inflammatory cytokines in a model of septic shock using C57BL/6 mice. Because macrophages are a good source of IL-12p70 and TNF-α, and are critical in driving adaptive immunity, we investigated the effect of Fh12 on the function of mouse bone marrow-derived macrophages (bmMΦs). Although Fh12 alone did not induce cytokine expression, it significantly suppressed the expression of IL-12, TNF-α, IL-6, and IL-1β cytokines, as well as inducible NO synthase-2 in bmMΦs, and also impaired the phagocytic capacity of bmMΦs. Fh12 had a limited effect on the expression of inflammatory cytokines induced in response to other TLR ligands. One mechanism used by Fh12 to exert its anti-inflammatory effect is binding to the CD14 coreceptor. Moreover, it suppresses phosphorylation of ERK, p38, and JNK. The potent anti-inflammatory properties of Fh12 demonstrated in this study open doors to further studies directed at exploring the potential of this molecule as a new class of drug against septic shock or other inflammatory diseases.

  18. Uptake of oleate by isolated rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut

    Energy Technology Data Exchange (ETDEWEB)

    Schwieterman, W.; Sorrentino, D.; Potter, B.J.; Rand, J.; Kiang, C.L.; Stump, D.; Berk, P.D.

    1988-01-01

    A portion of the hepatocellular uptake of nonesterified long-chain fatty acids is mediated by a specific 40-kDa plasma membrane fatty acid binding protein, which has also been isolated from the gut. To investigate whether a similar transport process exists in other tissues with high transmembrane fatty acid fluxes, initial rates (V/sub O/) of (/sup 3/H)-oleate uptake into isolated rat adipocytes were studied as a function of the concentration of unbound (/sup 3/H)oleate in the medium. V/sub O/ reached a maximum as the concentration of unbound oleate was increased and was significantly inhibited both by phloretin and by prior incubation of the cells with Pronase. A rabbit antibody to the rat liver plasma membrane fatty acid binding protein inhibited adipocyte fatty acid uptake by up to 63% in dose-dependent fashion. Inhibition was noncompetitive; at an immunoglobulin concentration of 250 ..mu..g/ml V/sub max/ was reduced from 2480 /plus minus/ 160 to 1870 /plus minus/ 80 pmol/min per 5 /times/ 10/sup 4/ adipocytes, with no change in K/sub m/. A basic kDa adipocyte plasma membrane fatty acid binding protein, isolated from crude adipocyte plasma membrane fractions, reacted strongly in both agar gel diffusion and electrophoretic blots with the antibody raised against the corresponding hepatic plasma membrane protein. These data indicate that the uptake of oleate by rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut.

  19. Clinical Usefulness of Urinary Fatty Acid Binding Proteins in Assessing the Severity and Predicting Treatment Response of Pneumonia in Critically Ill Patients: A Cross-Sectional Study.

    Science.gov (United States)

    Tsao, Tsung-Cheng; Tsai, Han-Chen; Chang, Shi-Chuan

    2016-05-01

    To investigate the clinical relevance of urinary fatty acid binding proteins (FABPs), including intestinal-FABP, adipocyte-FABP, liver-FABP, and heart-FABP in pneumonia patients required admission to respiratory intensive care unit (RICU).Consecutive pneumonia patients who admitted to RICU from September 2013 to October 2014 were enrolled except for those with pneumonia for more than 24 h before admission to RICU. Pneumonia patients were further divided into with and without septic shock subgroups. Twelve patients without infection were enrolled to serve as control group. Urine samples were collected on days 1 and 7 after admission to RICU for measuring FABPs and inflammatory cytokines. Clinical and laboratory data were collected and compared between pneumonia and control groups, and between the pneumonia patients with and without septic shock.There were no significant differences in urinary levels of various FABPs and inflammatory cytokines measured on day 1 between control and pneumonia groups. Urinary values of intestine-FABP (P = 0.020), adipocyte-FABP (P = 0.005), heart-FABP (P = 0.025), and interleukin-6 (P = 0.019) were significantly higher and arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2, P/F) ratio (P = 0.024) was significantly lower in pneumonia patients with septic shock on day 1 than in those without septic shock. After multivariate analysis, adipocyte-FABP was the independent factor (P = 0.026). Urinary levels of FABPs measured on day 7 of pneumonia patients were significantly lower in the improved than in nonimproved groups (P = 0.030 for intestine-FABP, P = 0.003 for adipocyte-FABP, P = 0.010 for heart-FABP, and P = 0.008 for liver-FABP, respectively). After multivariate analysis, adipocyte-FABP was the independent factor (P = 0.023).For pneumonia patients required admission to RICU, urinary levels of adipocyte-FABP on days 1 and 7 after admission to RICU may be valuable in assessing the

  20. Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation.

    Science.gov (United States)

    Ichikawa, Daisuke; Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Shibagaki, Yugo; Yasuda, Takashi; Katayama, Kimie; Hoshino, Seiko; Igarashi-Migitaka, Junko; Hirata, Kazuaki; Kimura, Kenjiro

    2014-03-15

    The aim of this study was to assess the renoprotective effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.

  1. Conjugated linoleic acid and fatty acid binding protein as antioxidants Ácido linoleico conjugado y proteína transportadora de ácidos grasos como antioxidantes

    Directory of Open Access Journals (Sweden)

    V.A. Piergiacomi

    2006-12-01

    Full Text Available Studies were carried out to determine the effect of conjugated linoleic acid (CLA and rat liver cytosolic protein enriched in fatty acid binding protein (FABP on the non-enzymatic lipid peroxidation of rat liver microsomes. The inhibition of lipid peroxidation was more evident when the FABP containing fraction obtained from CLA-group was used with either kind of microsomes (CLA and control. The chemiluminescence and polyunsaturated fatty acid composition of rat liver microsomes changed after CLA treatment. When native and peroxidized microsomes obtained from control group were compared, the most affected polyunsaturated fatty acids were: C18:2, C18:3 and C20:4, while in CLA-group C20:4 was mainly peroxidized The simultaneous analysis of chemiluminescence and fatty acid composition demonstrated that CLA and FABP play a role protecting rat liver microsomes against the harmful effect of lipid peroxidation.El objetivo del trabajo fue determinar el efecto del ácido linoleico conjugado (ALC y de la proteína citosólica de hígado de rata enriquecida en Proteína Transportadora de Ácidos Grasos (PTAG, sobre la peroxidación no enzimática de lípidos de microsomas hepáticos de rata. Luego de la incubación de éstos en un sistema ascorbato-Fe++ se observó que el total de cpm/mg de proteina originada por quimioluminiscencia fue menor en los microsomas obtenidos de las ratas del grupo ALC respecto a los del grupo control. Cuando la fracción PTAG obtenida del grupo ALC fue agregada a la peroxidación de microsomas de ambos grupos de animales ALC y control, la inhibición de la lipoperoxidación fue más evidente. Además se encontró que ambas fracciones PTAG, tanto la obtenida de animales del grupo ALC como la obtenida del grupo control, tuvieron mayor efecto como antioxidantes cuando se usaron microsomas ALC respecto a microsomas control. La composición de ácidos grasos de los microsomas cambió luego del tratamiento con ALC. Comparando

  2. Purification and initial characterization of the 71-kilodalton rat heat-shock protein and its cognate as fatty acid binding proteins.

    Science.gov (United States)

    Guidon, P T; Hightower, L E

    1986-06-03

    The major rat heat-shock (stress) protein and its cognate were purified to electrophoretic homogeneity from livers of heat-shocked rats. Both proteins exhibited similar behavior on a variety of column chromatography matrices but were separable by preparative isoelectric focusing under nondenaturing conditions by virtue of a 0.2 pH unit difference in isoelectric point. Both purified proteins had similar physical properties, suggesting the possibility that they may have similar biological functions as well. Both proteins were homodimers under nondissociative conditions (Mr 150 000) with isoelectric points of 5.0 (cognate) and 5.2 (major stress protein). After denaturation, both proteins had an increase in isoelectric point of 0.6 pH unit, and the resulting polypeptide chains had apparent molecular weights of 73 000 (cognate) and 71 000 (major stress protein). Similarities in the electrophoretic properties of these two proteins and serum albumin, which also undergoes a large basic shift in isoelectric point due to loss of fatty acids and conformational changes accompanying denaturation, prompted us to search for lipids associated with the purified 71-kilodalton stress protein and its cognate. Thin-layer chromatography of chloroform/methanol extracts of these two proteins revealed nonesterified fatty acids bound to both proteins. Palmitic acid, stearic acid, and a small amount of myristic acid were identified by gas chromatography/mass spectroscopy. Both proteins contained approximately four molecules of fatty acid per dimer with palmitate and stearate present in a one to one molar ratio. Possible roles of the major stress protein and its cognate as fatty acid associated proteins in cellular responses to stress are discussed.

  3. Diagnosis of Non-ST-Elevation Acute Coronary Syndrome by the Measurement of Heart-Type Fatty Acid Binding Protein in Serum: A Prospective Case Control Study

    Directory of Open Access Journals (Sweden)

    Priscilla Abraham Chandran

    2014-01-01

    Full Text Available A prospective case control study was undertaken to evaluate the diagnostic performance of serum heart-type fatty acid binding protein (HFABP in comparison to cardiac TnT and TnI in 33 patients admitted with chest pain, diagnosed as NSTE-ACS (non ST elevation acute coronary syndrome and 22 healthy controls. Area under the receiver operating curve (AUC was highest for H-FABP (AUC 0.79; 95% CI 0.66–0.89 versus cTnI (AUC 0.73; 95% CI 0.59–0.84 and cTnT (AUC 0.71; 95% CI 0.57–0.83. The H-FABP level above 6.5 ng/mL showed 56.7% (CI 37.4–74.5 sensitivity, 0.5 (95% CI 0.3–0.7 negative likelihood ratio (−LR, 100% (CI 84.6–100.0 specificity, and 100% (CI 79.4–100.0 positive predictive value (PPV, 62.9% (CI 44.9–78.5 negative predictive value (NPV. cTnI level above 0.009 μg/L had 40% (CI 22.7–59.4 sensitivity, 0.6 (95% CI 0.4–0.8 −LR, 100% (CI 84.6–100.0 specificity, 100% (CI 73.5–100.0 PPV, and 55% (CI 38.5–70.7 NPV. cTnT showed 46.7% (CI 28.3–65.7 sensitivity, 0.5 (95% CI 0.4–0.7 −LR, 100% (CI 84.6–100.0 specificity, 100% (CI 76.8–100.0 PPV, and 57.9% (CI 40.8–73.7 NPV at level above 9 μg/L. +LR were 12.5 (95% CI 1.8–86.8, 1.7 (95% CI 1.0–3.0, and 1.2 (95% CI 0.8–1.9 for H-FABP, cTnI, and cTnT respectively. In conclusion measurement of H-FABP is a valuable tool in the early diagnosis of patients with chest pain (6–8 hrs and seems to be a preferred biomarker in the differential diagnosis of NSTE-ACS. More studies are needed to determine whether serum H-FABP further improves diagnostic performance.

  4. 脂肪细胞型脂肪酸结合蛋白与肥胖及代谢综合征%Association of adipocyte fatty acid-binding protein with obesity and metabolism syndrome

    Institute of Scientific and Technical Information of China (English)

    黄岚; 邹大进

    2009-01-01

    脂肪细胞型脂肪酸结合蛋白(A-FABP)主要在脂肪组织中大量表达,其主要生理作用为参与细胞内部的脂肪酸转运和靶向定位.近期的研究发现,A-FABP是全身胰岛素敏感性以及糖脂代谢的重要调节冈素,与肥胖及代谢综合征的发生发展有紧密联系.%Adipocyte fatty acid-binding protein(A-FABP)belongs to the fatty acid-binding protein super-family, and it is highly expressed in adipose tissue.The physiologic function of A-FABP is involved in the intracellular trafficking and targeting of fatty acids inside cells.Recent research indicated that this protein may be all important regulator of systemic insulin sensitivity as well as lipid and glucose metabolism,indicating that A-FABP participates in the pathogenesis of obesity and metabolic syndrome.

  5. Sequence-specific {sup 1}H, {sup 13}C, and {sup 15}N resonance assignments for intestinal fatty-acid-binding protein complexed with palmitate (15.4 kDA)

    Energy Technology Data Exchange (ETDEWEB)

    Hodsdon, M.E.; Toner, J.J.; Cistola, D.P. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-12-01

    Intestinal fatty-acid-binding protein (I-FABP) belongs to a family of soluble, cytoplasmic proteins that are thought to function in the intracellular transport and trafficking of polar lipids. Individual members of this protein family have distinct specificities and affinities for fatty acids, cholesterol, bile salts, and retinoids. We are comparing several retinol- and fatty-acid-binding proteins from intestine in order to define the factors that control molecular recognition in this family of proteins. We have established sequential resonance assignments for uniformly {sup 13}C/{sup 15}N-enriched I-FABP complexed with perdeuterated palmitate at pH7.2 and 37{degrees}C. The assignment strategy was similar to that introduced for calmodulin. We employed seven three-dimensional NMR experiments to establish scalar couplings between backbone and sidechain atoms. Backbone atoms were correlated using triple-resonance HNCO, HNCA, TOCSY-HMQC, HCACO, and HCA(CO)N experiments. Sidechain atoms were correlated using CC-TOCSY, HCCH-TOCSY, and TOCSY-HMQC. The correlations of peaks between three-dimensional spectra were established in a computer-assisted manner using NMR COMPASS (Molecular Simulations, Inc.) Using this approach, {sup 1}H, {sup 13}C, and {sup 15}N resonance assignments have been established for 120 of the 131 residues of I-FABP. For 18 residues, amide {sup 1}H and {sup 15}N resonances were unobservable, apparently because of the rapid exchange of amide protons with bulk water at pH 7.2. The missing amide protons correspond to distinct amino acid patterns in the protein sequence, which will be discussed. During the assignment process, several sources of ambiguity in spin correlations were observed. To overcome this ambiguity, the additional inter-residue correlations often observed in the HNCA experiment were used as cross-checks for the sequential backbone assignments.

  6. Identification of okadaic acid binding protein 2 in reconstituted sponge cell clusters from Halichondria okadai and its contribution to the detoxification of okadaic acid.

    Science.gov (United States)

    Konoki, Keiichi; Okada, Kayo; Kohama, Mami; Matsuura, Hiroki; Saito, Kaori; Cho, Yuko; Nishitani, Goh; Miyamoto, Tomofumi; Fukuzawa, Seketsu; Tachibana, Kazuo; Yotsu-Yamashita, Mari

    2015-12-15

    Okadaic acid (OA) and OA binding protein 2 (OABP2) were previously isolated from the marine sponge Halichondria okadai. Because the amino acid sequence of OABP2 is completely different from that of protein phosphatase 2A, a well-known target of OA, we have been investigating the production and function of OABP2. In the present study, we hypothesized that OABP2 plays a role in the detoxification of OA in H. okadai and that the OA concentrations are in proportional to the OABP2 concentrations in the sponge specimens. Based on the OA concentrations and the OABP2 concentrations in the sponge specimens collected in various places and in different seasons, however, we could not determine a positive correlation between OA and OABP2. We then attempted to determine distribution of OA and OABP2 in the sponge specimen. When the mixture of dissociated sponge cells and symbiotic species were separated with various pore-sized nylon meshes, most of the OA and OABP2 was detected from the same 0-10 μm fraction. Next, when sponge cell clusters were prepared from a mixture of dissociated sponge cells and symbiotic species in the presence of penicillin and streptomycin, we identified the 18S rDNA of H. okadai and the gene of OABP2 in the analysis of genomic DNA but could not detect OA by LC-MS/MS. We thus concluded that the sponge cells express OABP2, and that OA was not apparently present in the sponge cells but could be colocalized with OABP2 in the sponge cells at a concentration less than the limit of detection.

  7. Nucleic acid binding properties of a helix stabilising nucleoid protein from the thermoacidophilic archaeon Sulfolobus acidocaldarius that condenses DNA into compact structures.

    Science.gov (United States)

    Celestina, F; Suryanarayana, T

    1995-12-01

    Helix stabilising nucleoid protein (HSNP-C') from an acidothermophilic archaeon Sulfolobus acidocaldarius has been characterised with respect to interaction with nucleic acids by gel retardation assay, binding to nucleic acid columns, fluorescence titrations and electron microscopy. The protein exists in solution as very large multimeric aggregates as indicated by cross-linking studies. The protein binds strongly and co-operatively to double stranded DNA. Electron microscopy of the complexes of the protein with DNA shows compact structures suggesting that the protein condenses DNA.

  8. Identification and functional characterization of the Arabidopsis Snf1-related protein kinase SnRK2.4 phosphatidic acid-binding domain

    NARCIS (Netherlands)

    Julkowska, M.M.; McLoughlin, F.; Galvan-Ampudia, C.S.; Rankenberg, J.M.; Kawa, D.; Klimecka, M.; Haring, M.A.; Munnik, T.; Kooijman, E.E.; Testerink, C.

    2015-01-01

    Phosphatidic acid (PA) is an important signalling lipid involved in various stress-induced signalling cascades. Two SnRK2 protein kinases (SnRK2.4 and SnRK2.10), previously identified as PA-binding proteins, are shown here to prefer binding to PA over other anionic phospholipids and to associate wit

  9. 脂肪酸结合蛋白与心脑血管病的早期诊断%Fatty acid-binding proteins and the early diagnosis of cardio-cerebrovascular diseases

    Institute of Scientific and Technical Information of China (English)

    张黎军; 赵中

    2010-01-01

    Currently, the commonly used diagnostic markers have the shortcomings of lower sensitivity or specificity in the early diagnosis of cardio-cerebrovascular diseases. Therefore, it needs to use the novel specific biochemical markers for the early diagnosis arid treatment, so as to decrease the high mortality and disability caused by cardio-cerebrovascular events. Fatty acid-binding proteins (FABPs) are a family of low-molecular-weight intracellular lipid-binding proteins. They are divided into 9 different subtypes, including the liver-, intestinal-, heart-, brain-, adipocyte-, skin-, ileal-, myelin-, and testis-subtype. Their primary function is to transport long-chain fatty acids into the cells, and thus regulate intracellular lipid metabolism. The structures of all FABP subtypes are similar, inclusive of two α2 helices arid one β2 fold structure. Among them, the sensitivities and specificities of the heart- and brain-subtype FABPs are higher in the early diagnosis of cardio-cerebrovascular diseases. It is promising to become the novel markers in the early diagnosis of cardio-cerebrovascular diseases.%在心脑血管病的早期诊断方面,目前常用的诊断标志物存在敏感性或特异性较低的缺点,因此需要利用新的生化特异标志物来进行早期诊断和早期治疗,以降低心脑血管事件导致的高病死率和高致残率.脂肪酸结合蛋白(fatty acid-binding protein,FABP)是一种低分子胞内脂质结合蛋白,分为肝脏型、肠型、心型、脑型、脂肪细胞型、表皮型、回肠型、髓磷脂型和睾丸型等9种亚型,其主要功能是转运长链脂肪酸至细胞内,从而调节细胞内脂质代谢.各种FABP亚型的结构相似,均含有2个α2螺旋和1个β2折叠结构.其中,心型和脑型FABP早期诊断心脑血管病的敏感性和特异性较高,有望成为心脑血管病早期诊断的新型标志物.

  10. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample) proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group) bred as either high- or low-capacity runners (HCR and LCR, respectively) that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897) and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5). Sixteen proteins were significantly (p ion (551.21 m/z) of the doubly-charged peptide SLGVGFATR (454.19 m/z) of residues 23-31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095) in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study) finding FABPH abundance was 2.23-fold greater (p = 0.0396) in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier

  11. Liver - fatty acid binding protein and renal disease%肝型脂肪酸结合蛋白(L-FABP)与肾脏疾病

    Institute of Scientific and Technical Information of China (English)

    孔祥雷; 许冬梅

    2008-01-01

    脂肪酸结合蛋白(FABPs)属于脂结合蛋白(lipid-binding proteins)超家族中的一类,根据其组织的特异性分布,可分为肝型(L-FABP)、小肠型(I-FABP)、心肌型(H-FABP)等9种.目前国外研究L-FABP在肾脏疾病中具有重要的意义,国内尚无报道,本文就L-FABP在肾脏疾病中的研究进展做一简要综述.

  12. 心型脂肪酸结合蛋白在急性冠状动脉综合征中的研究进展%Research of Heart-type Fatty Acid-Binding Protein in Acute Coronary Syndrome

    Institute of Scientific and Technical Information of China (English)

    黄艳

    2011-01-01

    Acute coronary syndrome ( ACS) is a major cause of death. In order to reduce the chances of cardiac deformity and death, it is important to diagnose ACS early and monitor its progression. Heart-type fatty acid-binding protein is a marker that has a high degree of specificity for the myocardium and may be viable as a diagnostic tool for early stage ACS. This article reviews the potential for ACS to serve as a biochemical cardiac marker for the early diagnosis of ACS.%急性冠状动脉综合征已成为严重危害人类健康的重要致死病因,它的早期预测及预防其进展,对它的发生率、致残率、病死率的降低具有重要意义.心型脂肪酸结合蛋白作为心肌损伤标志物,具有较高的心肌特异性,对于诊断早期急性冠状动脉综合征具有较高的敏感性和良好的特异性,更适合于临床急性冠状动脉综合征的早期诊断,对于心肌损伤诊断的准确性和及时性都会有极大的提高.

  13. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

    Science.gov (United States)

    Alqahtani, Mashael F; Smith, Craig M; Weiss, Scott L; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (psepsis.

  14. 大鼠非酒精性脂肪肝中L-FABP的动态表达%Expression of liver fatty acid binding protein in rat nonalcoholic fatty liver

    Institute of Scientific and Technical Information of China (English)

    冯爱娟; 陈东风

    2004-01-01

    目的:研究L-FABP(liver fatty acid binding protein)在大鼠非酒精性脂肪肝形成中的作用.方法:建立高脂饮食脂肪肝模型,用半定量逆转录聚合酶链反应(RT-PCR)与聚丙烯凝胶蛋白电泳(Western Blot)方法测定脂肪肝肝组织中L-FABP表达变化.结果:高脂饮食脂肪肝大鼠肝脏中L-FABP于2 wk时其mRNA及蛋白表达增强,于12 wk时表达最为明显,与正常组比较相差显著(1.42±0.034vs0.90±0.04;13 372.00±23.86vs6857.33±32.9 6637;P<0.05).结论:高脂饮食引起L-FABP表达增强,最初是一种适应性反应,随着L-FABP表达进一步增强,导致脂肪酸代谢失衡,引起脂肪肝的发生.

  15. Fatty acid binding protein in children with obesity%脂肪酸结合蛋白与肥胖的关系

    Institute of Scientific and Technical Information of China (English)

    武明雷

    2013-01-01

    随着人们生活水平的提高、饮食结构的改变,肥胖问题凸显,已成为严重威胁人类健康的重要隐患.在这个庞大的群体中,儿童所占比例越来越高.在肥胖的相关研究领域中,许多因子扮演着重要角色,其中脂肪酸结合蛋白在肥胖发生发展中的作用近年来成为研究热点.该文就脂肪酸结合蛋白与儿童肥胖之间的联系作一综述.%With the improvement of living standards and dietary changes,obesity has become a serious threat to human health.In this huge group,the proportion of children is increasing.Many factors play significant roles in obesity-related research areas.Fatty acid blinding protein has become a hot topic in recent years.

  16. Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

    Directory of Open Access Journals (Sweden)

    Mas Rizky A A Syamsunarno

    Full Text Available Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA utilization, are disturbed. FA binding protein 4 (FABP4 and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice, as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT and glycogen in skeletal muscle (SkM was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.

  17. Selective staining of CdS on ZnO biolabel for ultrasensitive sandwich-type amperometric immunoassay of human heart-type fatty-acid-binding protein and immunoglobulin G.

    Science.gov (United States)

    Qin, Xiaoli; Xu, Aigui; Liu, Ling; Sui, Yuyun; Li, Yunlong; Tan, Yueming; Chen, Chao; Xie, Qingji

    2017-05-15

    We report on an ultrasensitive metal-labeled amperometric immunoassay of proteins, which is based on the selective staining of nanocrystalline cadmium sulfide (CdS) on ZnO nanocrystals and in-situ microliter-droplet anodic stripping voltammetry (ASV) detection on the immunoelectrode. Briefly, antibody 1 (Ab1), bovine serum albumin (BSA), antigen and ZnO-multiwalled carbon nanotubes (MWCNTs) labeled antibody 2 (Ab2-ZnO-MWCNTs) were successively anchored on a β-cyclodextrin-graphene sheets (CD-GS) nanocomposite modified glassy carbon electrode (GCE), forming a sandwich-type immunoelectrode (Ab2-ZnO-MWCNTs/antigen/BSA/Ab1/CD-GS/GCE). CdS was selectively grown on the catalytic ZnO surfaces through chemical reaction of Cd(NO3)2 and thioacetamide (ZnO-label/CdS-staining), due to the presence of an activated cadmium hydroxide complex on ZnO surfaces that can decompose thioacetamide. A beforehand cathodic "potential control" in air and then injection of 7μL of 0.1M aqueous HNO3 on the immunoelectrode allow dissolution of the stained CdS and simultaneous cathodic preconcentration of atomic Cd onto the electrode surface, thus the following in-situ ASV detection can be used for immunoassay with enhanced sensitivity. Under optimized conditions, human immunoglobulin G (IgG) and human heart-type fatty-acid-binding protein (FABP) are analyzed by this method with ultrahigh sensitivity, excellent selectivity and small reagent-consumption, and the limits of detection (LODs, S/N=3) are 0.4fgmL(-1) for IgG and 0.3fgmL(-1) for FABP (equivalent to 73 FABP molecules in the 6μL sample employed).

  18. Fatty acid binding proteins (FABPs in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Jung Klaus

    2011-07-01

    Full Text Available Abstract Background Fatty acid binding proteins (FABP play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Methods Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. Results General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Conclusions Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the

  19. Relationship of Urinary Liver-Type Fatty Acid-Binding Protein to Kidney Damage in Diabetic Patients%尿肝型脂肪酸结合蛋白与糖尿病肾损伤的相关性

    Institute of Scientific and Technical Information of China (English)

    曾宪飞; 李军民; 谈昀; 王小刚

    2013-01-01

    目的 探讨在1型和2型糖尿病患者中尿肝型脂肪酸结合蛋白(liver-type fatty-acid binding protein,L-FABP)与糖尿病肾损伤程度的关系.方法 选择2011年8月~10月门诊确诊1型糖尿病患者119例,2型糖尿病患者128例,以及103例体检确认的健康者,依据尿蛋白/血肌酐比(albumin-to-creatinine rate,ACR)和血清肌酐水平将糖尿病确诊患者分为无蛋白尿组(ACR176.8 mmol/L).酶联免疫吸附法(ELISA)测定受试者尿L-FABP浓度,同时检测全血糖化血红蛋白(HbA1c)、血清肌酐(Scr)、尿肌酐、尿清蛋白和尿胱抑素C等指标,MDRD校正方程估算肾小球滤过率(eGFR).结果 健康人群尿L-FABP水平为13.0(10.8~14.8)μg/g·cr,95%参考值范围为9.0~17.5 μg/g·cr;随着糖尿病肾损伤程度的加重,尿L-FABP水平增高(各组间比较H=282.5,P0.05).结论 尿L-FABP水平能准确反映糖尿病肾损伤程度,可作为诊断糖尿病肾损伤的标志物.%Objective To study the relationship of urinary liver type fatty acid binding protein (L FABP) and kidney damage in type 1 and 2 diabetic patients. Methods 103 healthy subjects from physical examination people and 247 diabetic patients (119 type 1 and 128 type 2) from outpatients were recruited in this study. Patients were divided into four diabetic nephropa thy groups based on the degree of albumin to creatinine rate or renal function,as follows:normoalbuminuria (ACR176. 8 mmol/L). Urinary L FABP was measured by ELISA and whole blood HbAlc,serum creati nine,urinary creatiine,urinary albumin,and urinary cstatin C were measured by respective biochemical or immunological methods. MDRD equation was used to evaluate the glomemlar filtration rate. Results The level of urinary L FABP was 13. 0 (10. 8~14. 8)μg/g · cr in 103 healthy subjects. The high urinary L FABP levels were associated with the progression of dia betic nephropathy. There was a significant difference of urinary L FABP among groups ( H= 282. 5, P<0. 005

  20. 心脏型脂肪酸结合蛋白对急性肺栓塞早期预后评估的价值%Prognostic Value of Heart Type Fatty Acid Binding Protein in Acute Pulmonary Embolism

    Institute of Scientific and Technical Information of China (English)

    黄奕奕; 沈翔; 张淑云

    2015-01-01

    Objective To assess the value of heart type fat y acid binding protein (H-FABP)for prognosis of patients with acute pulmonary embolism(APE).Methods There were 51 patients with APE, divided into two groups:H-FABP≥10μg/l group (n=21)and H-FABP<10μg/l group (n=30),The relations between H-FABP and risk stratification and prognosis evaluating were evaluated in the two groups.Results In the positive group,there were 9 high-risk PE,10 middle-risk PE,2 low-risk PE,6 died within 1 months.In the negative group,there were 4 high-risk PE,14 middle-risk PE,12 low-risk PE,2 died within 1 months. There was statistical significance in the occur ence of hypotension,right heart dysfunction and myocardial damage between the two groups ( <0.05).Also there was statistical significance in the cases with high-risk,low-risk and death( <0.05).Conclusion H-FABP is a reliable predictor of short-term of patient with APE.%目的:探讨心脏型脂肪酸结合蛋白(heart type fat y acid binding protein,H-FABP)水平对急性肺栓塞(acute pulmonary embolism,APE)早期预后的评估价值。方法51例急性肺栓塞患者根据H-FABP测定值分为阳性组21例(H-FABP≥10μg/l)及阴性组30例(H-FABP<10μg/l),分析H-FABP升高对APE患者危险分层与临床预后的关系。结果阳性组中高危9例,中危10例,低危2例,死亡6例。阴性组中高危4例,中危14例,低危12例,死亡2例。两组比较低血压、右心室功能不全以及心肌损伤的发生率之间差异有统计学意义(<0.05);在高危、低危及1月内死亡人数方面相比差异亦具有统计学意义(<0.05)。结论 H-FABP对急性肺栓塞患者的早期预后判定有着很好的相关性。

  1. Critical review and meta-analysis on the combination of heart-type fatty acid binding protein (H-FABP) and troponin for early diagnosis of acute myocardial infarction.

    Science.gov (United States)

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco

    2013-01-01

    An early diagnosis is crucial for effective triage and management of patients with suspected acute myocardial infarction (AMI). Although troponin testing is the cornerstone of diagnosis, the sensitivity of this biomarker is still suboptimal at patient admission. The heart-type fatty acid binding protein (H-FABP) is an early and sensitive biomarker of myocardial ischemia, whose appropriate setting is in combination with troponin testing. We performed a systematic review and meta-analysis of articles that have assessed the combination of troponin and H-FABP in the early diagnosis of AMI. Eight studies, totaling 2735 patients, met the inclusion criteria but none of them used a high-sensitivity troponin immunoassay. The between-study variation was high (98.5%), and attributable to heterogeneity. When considered alone, troponin exhibited a significantly greater pooled area under the curve (AUC) than H-FABP alone (0.820 versus 0.784; ptroponin alone than for H-FABP alone (0.94 versus 0.83; ptroponin than for H-FABP (0.73 versus 0.80; p=0.02). The combination of both biomarkers exhibited a greater AUC than troponin alone (0.881; ptroponin immunoassay seems advantageous for increasing the sensitivity of the former biomarker, at the expense of a lower specificity. The introduction of H-FABP testing would hence require careful assessment of laboratory data or clinical signs and symptoms for excluding sources of elevation different from AMI. Further studies are needed to assess the diagnostic effectiveness of combining H-FABP with a high-sensitivity troponin immunoassay.

  2. Recent Studies in Clinical Application of Heart Fatty Acid Binding Protein in Pediatric Diseases%心型脂肪酸结合蛋白在儿科疾病的临床应用新进展

    Institute of Scientific and Technical Information of China (English)

    李婷(综述); 徐家丽(审校)

    2015-01-01

    Heart-type fatty acid binding protein ( H-FABP) is one of the promising biological markers for the evaluation of myocardial injury.H-FABP is known to be rapid released from injured myocardium into the blood.With the progress of the study, it is discovered that H-FABP is also expressed in brain, skeletal muscle,lung,kidney,adrenal,mammary gland and so on.Because it is an effective marker for early diagno-sis,risk stratification,and assessing prognosis,it′s more and more widely applied in clinical.At present,the study of H-FABP is focused on adult disease,but rarely reported in pediatric disease.%心型脂肪酸结合蛋白( H-FABP)是评价心肌组织损伤的一种更为敏感的新型生物标志物,其能从损伤的心肌组织中快速释放到血液中。随着对H-FABP越来越深入的研究,研究者发现其也在脑、骨骼肌、肺、肾、肾上腺和乳腺等组织中表达,故其在临床中的应用(如早期诊断、危险分层、预后评估等)越来越广泛。目前的研究主要集中在成人疾病中,在儿科疾病中报道不多。

  3. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects.

    Science.gov (United States)

    Weickert, Martin O; Loeffelholz, Christian V; Roden, Michael; Chandramouli, Visvanathan; Brehm, Attila; Nowotny, Peter; Osterhoff, Martin A; Isken, Frank; Spranger, Jochen; Landau, Bernard R; Pfeiffer, Andreas F H; Möhlig, Matthias

    2007-10-01

    Liver fatty acid-binding protein (L-FABP) is a highly conserved key factor in lipid metabolism. Amino acid replacements in L-FABP might alter its function and thereby affect glucose metabolism in lipid-exposed subjects, as indicated by studies in L-FABP knockout mice. Amino acid replacements in L-FABP were investigated in a cohort of 1,453 Caucasian subjects. Endogenous glucose production (EGP), gluconeogenesis, and glycogenolysis were measured in healthy carriers of the only common Thr(94)-to-Ala amino acid replacement (Ala/Ala(94)) vs. age-, sex-, and BMI-matched wild-type (Thr/Thr(94)) controls at baseline and after 320-min lipid/heparin-somatostatin-insulin-glucagon clamps (n = 18). Whole body glucose disposal was further investigated (subset; n = 13) using euglycemic-hyperinsulinemic clamps without and with lipid/heparin infusion. In the entire cohort, the only common Ala/Ala(94) mutation was significantly associated with reduced body weight, which is in agreement with a previous report. In lipid-exposed, individually matched subjects there was a genotype vs. lipid-treatment interaction for EGP (P = 0.009) driven mainly by reduced glycogenolysis in Ala/Ala(94) carriers (0.46 +/- 0.05 vs. 0.59 +/- 0.05 mgxkg(-1)xmin(-1), P = 0.013). The lipid-induced elevation of plasma glucose levels was smaller in Ala/Ala(94) carriers compared with wild types (P glycogenolysis and less severe hyperglycemia in lipid-exposed humans and was further associated with reduced body weight in a large cohort. Data clearly show that investigation of L-FABP phenotypes in the basal overnight-fasted state yielded incomplete information, and a challenge test was essential to detect phenotypical differences in glucose metabolism between L-FABP genotypes.

  4. A newly developed kit for the measurement of urinary liver-type fatty acid-binding protein as a biomarker for acute kidney injury in patients with critical care.

    Science.gov (United States)

    Sato, Ryo; Suzuki, Yasushi; Takahashi, Gaku; Kojika, Masahiro; Inoue, Yoshihiro; Endo, Shigeatsu

    2015-03-01

    In recent years, it has been reported that the urinary level of Liver-type fatty acid-binding protein (L-FABP) serves as a useful biomarker for diagnosing acute kidney injury (AKI) or sepsis complicated by AKI. However, because the urinary level of L-FABP is currently measured by enzyme-linked immunosorbent assay (ELISA), several days may elapse before the results of the measurement become available. We have newly developed a simplified kit, the Dip-test, for measuring the urinary level of L-FABP. The Dip-test was measured at 80 measurement points (22 points in noninfectious disease, 13 points in SIRS, 20 points in infectious disease, and 25 points in sepsis) in 20 patients. The urinary L-FABP levels as determined by ELISA in relation to the results of the Dip-test were as follows: 10.10 ± 12.85 ng/ml in patients with a negative Dip-test ([-] group), 41.93 ± 50.51 ng/ml in patients with a ± test ([±] group), 70.36 ± 73.70 ng/ml in patients with a positive test ([+] group), 1048.96 ± 2117.68 ng/ml in patients with a 2 + test ([2+] group), and 23,571.55 ± 21,737.45 ng/ml in patients with a 3 + test ([3+] group). The following tendency was noted: the stronger the positive Dip-test reaction, the higher the urinary L-FABP level. Multigroup comparison revealed a significant differences in the urinary L-FABP levels between the Dip-test (-) group and each of the other groups. In this study, the usefulness of the Dip-test, our newly developed simplified kit for measuring the urinary L-FABP level, is suggested.

  5. Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

    Science.gov (United States)

    Maeda, Yoshiteru; Suzuki, Atsushi; Ishii, Junnichi; Sekiguchi-Ueda, Sahoko; Shibata, Megumi; Yoshino, Yasumasa; Asano, Shogo; Hayakawa, Nobuki; Nakamura, Kazuhiro; Akiyama, Yasukazu; Kitagawa, Fumihiko; Sakuishi, Toshiaki; Fujita, Takashi; Hashimoto, Shuji; Ozaki, Yukio; Itoh, Mitsuyasu

    2015-05-01

    Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

  6. СHARACTERISTICS OF THE HEART FATTY ACID-BINDING PROTEIN, INTERLEUKIN-6 AND INTERLEUKIN-8 AS ALTERNATIVE MARKERS OF DIABETIC NEPHROPATHY PROGRESSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Yu. A. Ryzhikova

    2015-01-01

    Full Text Available The aim of this work was to study the levels of the heart fatty acid-binding protein (h-FABP, interleukin6 (IL-6 and interleukin-8 (IL-8, in diabetic nephropathy (DN in patients with type 1 diabetes mellitus (T1DM. Material and methods. We examined 87 patients aged 18 to 54 with T1DM within the study group. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients – with proteinuria. The control group consisted of 24 healthy donor aged 22 to 29. The comparison group included 22 patients aged 20 to 42 with verified diagnosis of essential arterial hypertension (AH without carbohydrate metabolism disorders. The daily urinary albumin excretion was determined by immunoturbidimetric technique. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients with proteinuria.Calculation of glomerular filtration rate was performed according to the Hoek formula with the use of cystatinС serum concentrations. Contents of h-FABP, IL-6 and cystatin C in serum and h-FABP, IL-8 inurine were determined by enzyme-linked immunosorbent assay. Results. Analysis of the h-FABP content in serum showed that the concentration of this marker in individuals with T1DM was higher than in patients of the control group and the comparison group. Analysis of the h-FABP content in the urine revealed that individuals with essential hypertension showed an increased level of h-FABP while patients with T1DM demonstrated the highest concentration of h-FABP. The concentration of IL-6 inindividuals with T1DM and in individuals with AH significantly exceeded the control values. The contents of h-FABP and IL-6 inserum and h-FABP and IL-8 inurine increased with the progression of DN and reached maximum in individuals of the proteinuria subgroup. At the same time, the levels of h-FABP and IL-8 inthe urine of patients in the microalbuminuria (MAU subgroup were

  7. Clinical Value of Heart Type Fatty Acid-binding Protein in Pulmonary Disease%心型脂肪酸结合蛋白在肺疾病中的临床应用进展

    Institute of Scientific and Technical Information of China (English)

    王宇宏; 李敏

    2015-01-01

    The heart type fatty acid-binding protein (H-FABP) as a new biological marker receives closely attention in recent years. It characteristics of high specificity and strong sensitivity and has a value to screen early myocardial damage. When pulmonary parenchyma and pulmonary vascular disease involved right heart function, the prognosis is poor. Always, the majority of patients died from right heart failure. If we can early detect myocardial injury, we would take measures as soon as possible. H-FABP can be used as a marker of early myocardial damage caused by pulmonary disease. The detection of H-FABP can be help for assessment risk stratification and prognosis. In this paper, we reviewed the clinical value of H-FABP in acute pulmonary embolism (APE), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), obstructive sleep apnea hypopnea syndrome (OSAHS) in recent years.%心型脂肪酸结合蛋白(H-FABP)作为一种新生的生物学标志物近些年来获得研究者们的青睐,它是心肌损伤早期检测的标志物,具有高度特异性及敏感性。肺组织和肺血管疾病因并发右心功能不全而预后差,大部分患者死于右心衰竭。若临床早期发现肺疾病所致心肌受损,则有利于及早采取治疗措施,延缓病情进展。H-FABP可以作为所致肺疾病早期心肌损伤检测的标志物,用于评估病情危险程度及预后。本文就近年来H-FABP在急性肺栓塞(APE),慢性阻塞性肺疾病(COPD)、肺动脉高压(PH)、呼吸睡眠暂停(OSAHS)等疾病的临床应用进行综述。

  8. Relationship between serum adipocyte fatty acid-binding protein and coronary heart disease%脂肪细胞型脂肪酸结合蛋白与冠心病临床相关性的研究

    Institute of Scientific and Technical Information of China (English)

    牛海军; 张宁汝; 张恒; 刘进军; 李妙男; 王本芳; 耿家峰

    2012-01-01

    目的:比较不同类型、不同病变支数冠心病患者的血清脂肪细胞型脂肪酸结合蛋白(A-FABP)的血清水平,分析其与冠心病的关系.方法:选择冠心病患者64例,同期造影阴性对照组24例.采用固相夹心酶偶联免疫吸附法(ELISA)检测A-FABP、白细胞介素6(IL-6)含量,免疫散射比浊法测定血清高敏C反应蛋白(hs-CRP).结果:A-FABP水平在对照组[5.96(4.87~7.99)ng/ml]较冠心病组[7.76(6.28~9.12)ng/ml]明显降低(P<0.05).A-FABP水平在多支病变组[9.33(8.04~11.09)ng/ml]较单支病变组[6.61(5.62~7.59)ng/ml](P<0.01)高.A-FABP与IL-6呈正相关(r=0.592,P<0.01),与hs-CRP呈正相关(r=0.604,P<0.01).Logistic回归分析示血清A-FABP水平与冠心病危险度呈正相关(x2=21.734,P<0.01).结论:血清A-FABP水平与冠心病的病变程度、IL-6、hs-CRP及冠心病危险度呈正相关.%Objective:To detect the serum adipocyte fatty acid-binding protein (A-FABP) in patients with coronary heart disease (CHD). Methods: 64 patients with CHD and 24 controls with normal coronary arteris were enrolled. Serum A-FABP and interleukin-6 (IL-6) were detected by ELISA, while serum hs-CRP was detected by immunoturbidimetry. Results:Serum A-FABP was significantly higher in patients with CHD [7. 76(6. 28 —9. 12) ng/ml] than that in control group [5. 96(4. 87 — 7. 99)ng/ml] (P<0. 05). Serum A-FABP in multi-vessel lesions group [9. 33(8. 04—11. 09)ng/ml] was significantly higher than that in single-vessel lesion group [6. 61(5. 62—7. 59)ng/ml] (P<0. 01). Serum A-FABP positively correlated with serum IL-6 (r=0. 592, P<0. 01) and hs-CRP (r=0. 604, P<0. 01). Logistic regression analysis showed that serum A-FABP level and CHD were closely related (x2 =21. 734, P<0. 01). Conclusion:Serum levels of A-FABP is positively correlated with the coronary lesions, IL-6, hs-CRP, which may be a risk factor of CHD.

  9. The change and significance of heart fatty acid-binding protein and cardiac troponin Ⅰ in valve replacement patients%心脏瓣膜置换围手术期H-FABP和cTnI的变化及意义

    Institute of Scientific and Technical Information of China (English)

    陈志军; 王永连; 王忠民

    2011-01-01

    目的 探讨心脏瓣膜置换术后心肌肌钙蛋白I(cTnI)和心型脂肪酸结合蛋白(H-FABP)的变化规律.方法 选本院风湿性心脏病手术患者40例,随机分为晶体停搏液灌注组和冷血停搏液灌注组,选取8个时间点,分析和比较各时点血清cTnI和H-FABP浓度变化规律.结果 晶体停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=2744.397,P<0.01; F交互=125.345,P<0.01),冷血停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=1056.357,P<0.01; F交互 =64.242,P<0.01);晶体停搏液灌注组H- FABP组间及交互效应差异均有统计学意义(F组间=1775.022,P<0.01;F交互=34.297,P<0.01),冷血停搏液灌注组H -FABP组间及交互效应差异均有统计学意义(F组间=3064.451,P<0.01;F交互=60.472,P<0.01).结论 H-FABP心肌的特异性强,有效诊断窗口期短,较符合心肌损伤的理想判定标志物.%Objective To explore change trend of Cardiac Troponin Ⅰ (cTnI) and Heart Fatty Acid-binding Protein(H-FABP) in serum during the perioperation of valve replacement.Methods Forty patients with heumatoid valvular heart disease were selected for this study,and the patients were randomly divided into two groups.Blood samples were taken from center vein,and the serum levels of cTnI and H-FABP were determined.The change of the serum levels of these two markers at different time points was recorded and compared between two groups.Results There were significant differences in the concentration of cTnl in the cold crystalloid cardioplegia group ( F between group =2744.397,P <0.01 ; F interaction =125.345,P <0.01 ).There were significant differences in the concentration of cTnI in the cold blood cardioplegia group ( F between group =1056.357,P < 0.01 ; Finteraction =64.242,P < 0.01 ).There were significant differences in the concentration of H - FABP in the cold crystalloid cardioplegia group ( F between group =1775.022,P <0.01; F

  10. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

    Directory of Open Access Journals (Sweden)

    Mashael F Alqahtani

    Full Text Available Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1, mid-regional pro-atrial natriuretic peptide (mrProANP, and adipocyte fatty-acid-binding proteins (A-FaBPs have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n were reduced on day 1 (0.024, 0.004-0.174, 13, day 2 (0.020, 0.002-0.109, 10, and day 3 (0.018, 0.003-0.058, 23 compared with febrile (0.705, 0.187-1.778, 22 and healthy (0.7, 0.4-1.2, 29 (p< 0.05 controls. A-FaBP and mrProANP (Median, IQR ng/mL, n were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05. The area under the curve (AUC for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05. A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05. MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05. A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7 were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11. MMP-9/TIMP-1 ratios were

  11. The human YB-1 cold shock domain : structural, dynamical and binding properties of the central nucleic acid binding domain of the human Y-box protein YB-1, a transcription and translation regulating protein

    NARCIS (Netherlands)

    Kloks, Cathelijne Petra Anne Marie

    2003-01-01

    Y-box proteins are a highly conserved group of proteins present in bacteria, plants and animals. They are essential in regulating transcription and translation and the coupling between theses two processes. Their central domain, the so-called cold shock domain (CSD), is responsible for the nucleic a

  12. The 18-kilodalton Chlamydia trachomatis histone H1-like protein (Hc1) contains a potential N-terminal dimerization site and a C-terminal nucleic acid-binding domain

    DEFF Research Database (Denmark)

    Pedersen, LB; Birkelund, Svend; Holm, A

    1996-01-01

    , in part, be due to Hc1-mediated alterations of DNA topology. To locate putative functional domains within Hc1, polypeptides Hc1(2-57) and Hc1(53-125), corresponding to the N- and C-terminal parts of Hc1, respectively, were generated. By chemical cross-linking with ethylene glycol-bis (succinic acid N...... retardation assays, Hc1(53-125) was shown to contain a domain capable of binding both DNA and RNA. Under the same conditions, Hc1(2-57) had no nucleic acid-binding activity. Electron microscopy of Hc1-DNA and Hc1(53-125)-DNA complexes revealed differences suggesting that the N-terminal part of Hc1 may affect...

  13. Significance of heart-type fatty acid binding protein in patients with acute coronary syndrome%心脏型脂肪酸结合蛋白在急性冠脉综合征中检测的意义

    Institute of Scientific and Technical Information of China (English)

    王斌

    2014-01-01

    目的:探讨心脏型脂肪酸结合蛋白(H-FABP)在急性冠脉综合征中检测的意义。方法将102例急性冠脉综合征分为不稳定型心绞痛(UA)35例,非 ST 段抬高急性心肌梗死(NSTEMI)49例和 ST 段抬高急性心肌梗死(STEMI)18例。另外选择40例健康人为正常组。测定血清肌钙蛋白(cTnI)和 H-FABP。结果 UA、NSTEMI、STEMI 组血清 cTnI 和 H-FABP 均高于正常组(P ﹤0.01),NSTEMI 组血清 cTnI 和 H-FABP 均高于 UA 组( P ﹤0.01),STEMI 组血清 cTnI 和 H-FABP 均高于 NSTEMI 组(P ﹤0.01)。在胸痛发作后2、4、6 h 血清中 H-FABP 阳性率明显高于 cTnI 阳性率,两者比较差异有统计学意义(P ﹤0.05),胸痛发作后12 h,血清中 H-FABP 阳性率明显低于 cTnI 阳性率,两者比较差异有统计学意义(P ﹤0.05)。血清 cTnI 和 H-FABP 在高危组均高于中危组、低危组(P 均﹤0.05),在中危组高于低危组(P 均﹤0.05)。血清 cTnI 和 GRACE 评分呈正相关(r =0.27,P ﹤0.05),血清H-FABP 和 GRACE 评分呈正相关(r =0.58,P ﹤0.05)。血清 H-FABP 和 GRACE 评分的相关系数大于血清 cTnI 和GRACE 评分的相关系数。结论 H-FABP 对急性冠脉综合征的诊断和危险分层更敏感。%Objective To study the significance of heart-type fatty acid binding protein( H-FABP)in patients with acute coronary syndrome. Methods One hundred and two cases of acute coro-nary syndrome were divided into unstable angina(UA)(35 cases),non-ST segment elevation acute my-ocardial infarction(NSTEMI)(49 cases)and ST segment elevation acute myocardial infarction(STE-MI)(18 cases). Forty cases of normal healthy people were enrolled into the normal group. Serum cTnI and H-FABP levels were detected. Results Serum cTnI and H-FABP levels in UA,NSTEMI,STEMI were higher than those in the normal group(P ﹤ 0. 01). Serum cTnI and H-FABP levels in NSTEMI were higher than those in the UP

  14. 川崎病患儿心型脂肪酸结合蛋白和脑利钠肽的变化及与心功能的关系%Changes of serum heart type fatty acid binding protein and brain natriuretic peptide and their clinical significance in children with Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    王金菊; 陈宗波; 王文棣

    2015-01-01

    Objective To explore the serum levels changes of heart-type fatty acid-binding protein and brain natriuretic peptide in children with Kawasaki disease,as well as their links with the heart function. Methods A total of 53 children with Kawasaki disease admitted to our hospital from February 2008 to March 2012 were selected and at the same time 50 healthy controls were randomly selected. The serum levels for the children in acute phase,recovery period of Kawasaki disease and control group children were determined by en-zyme-linked immnoabsorbent assay. The internal diameter of coronary artery,LVEF,LVSF,CI and E/A of chil-dren were measured by two-dimensional echocardiography. Results The heart-type fatty acid-binding protein and brain natriuretic peptide concentrations of children with Kawasaki disease in acute stage[(18. 23 ± 13. 81) ng/ml,(517. 2 ±213. 2) pg/ml] were higher than those in recovery stage[(6. 29 ± 1. 26) ng/ml,(92. 1 ± 46. 0) pg/ml](P<0. 05). They were also higher for children in acute stage than those of control group[(6. 26 ± 1. 60) ng/ml,(37. 6 ± 7. 6) pg/ml]. The LVEF,LVSF,CI of Kawasaki disease for children in acute stage were lower than those in recovery phase[(60. 3 ± 3. 6)% vs. (64. 8 ± 4. 3)%,(30. 6 ± 2. 5)% vs. (34. 9 ± 1. 9)%,(3. 1 ± 0. 3)% vs. (3. 5 ± 0. 3)%]. Linear correlation analysis showed the heart-type fatty acid-binding protein and brain natriuretic peptide′concentrations in Kawasaki disease were negatively correlated with LVEF (P<0. 05). The heart-type fatty acid-binding protein′positive rates were also higher than brain natriuretic peptide for the children in acute and recovery phase. Conclusion The heart-type fatty acid-binding protein and brain na-triuretic peptide could be used as the biochemical markers for myocardial damage of children with Kawasaki dis-ease. The heart-type fatty acid-binding protein was more significant than brain natriuretic peptide. The heart-type fatty acid-binding protein and brain

  15. 缺血修饰清蛋白和心型脂肪酸结合蛋白检测在不稳定性心绞痛诊断及危险分层中的应用%Application of ischemia modified albumin and heart-type fatty acid-binding protein for the diagnosis and risk stratification of unstable angina

    Institute of Scientific and Technical Information of China (English)

    辛增莲; 杨丽; 郭宇璇; 彭辉; 徐菲莉

    2015-01-01

    Objective To determine the value of ischemia modified albumin,heart-type fatty acid-binding protein,B-type natri-uretic peptide and homocysteine in the risk stratification of patients with unstable angina pectoris;thus to provide an assessment for the condition of patients in clinic.Methods 135 patients with unstable angina were included in the disease group and subjected to risk stratification according to GRACE risk score software,70 cases of low-risk group,60 cases in the middle-risk group and 5 cases in the high-risk group.Another 145 healthy people were in the control group.The levels of ischemia modified albumin,heart-type fatty acid-binding protein,B-type natriuretic peptide and homocysteine were detected and compared.Results Between the control group and the disease group,significant difference of heart-type fatty acid-binding protein,B-type natriuretic peptide and homocys-teine was found (P 0.05).In the dis-ease group,the levels of ischemia modified albumin,heart-type fatty acid-binding protein and homocysteine in each risk stratification showed no significant difference(P >0.05).The level of B-type natriuretic peptide in high-risk group was higher than that in the low-risk group and in the middle-risk group and the difference was statistically significant (P 0.05 ).Conclusion The detection of heart-type fatty acid-binding protein,B-type natriuretic peptide and homocysteine possesses certain meaning in diagnosing unstable angi-na,and the level of B-type natriuretic peptide indicates the risk degree of the disease.%目的:探讨血清缺血修饰清蛋白(IMA)、心型脂肪酸结合蛋白(H-FABP)、B 型利钠肽(BNP)、同型半胱氨酸(Hcy)与不稳定性心绞痛(UA)危险分层的关联性,为临床提供评估患者病情的依据。方法选取135例不稳定性心绞痛(UA)患者作为病例组,根据全球急性冠状动脉事件注册(GRACE)危险评分软件,将病例组分为低危组70例、中危组60例及高危组5

  16. Correlation of intestinal fatty acid binding protein and intestinal injury in severe sepsis%肠脂肪酸结合蛋白与严重脓毒症患者肠道损伤的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱承睿; 丁仁彧; 孙旖旎; 马晓春

    2014-01-01

    Objective To investigate the content of intestinal fatty acid binding protein (IFABP) and its clinical significance in patients with severe sepsis.Methods A prospective observational study was conducted.Fifty patients with severe sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from July to December 2012 were enrolled,and 20 healthy patients served as control group.The concentrations of serum IFABP,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) were determined with enzyme-linked immunosorbent assay (ELISA) on days 0,1 and 3 after ICU admission.Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score,28-day prognosis,acute gastrointestinal injury (AGI) grade were recorded at the same time.Furthermore,the contents of IFABP were compared between control group and the severe sepsis group,abdominal infection group and non-abdominal infection group,the survival group and the death group,as well as among different AGI-grade groups.Correlation analysis of IFABP and inflammatory factors,IFABP and two scores,and IFABP and time of stay in ICU and mechanical ventilation were studied.Multivariate logistic regression and analysis of 28-day outcome of the patients were also studied.Results IFABP levels were increased in severe sepsis patients on days 0,1 and 3 compared with those of healthy control group (mg/L:731.90 ±53.91,592.07 ±41.94,511.85 ±47.97 vs.439.88 ±23.68,all P =0.000).There was no statistical significance of IFABP levels between abdominal infection group and non-abdominal infection group,the survival group and the death group,or among different AGI-grade groups.The correlation analysis showed that IFABP was statistically related with IL-6 (r=0.794,P=0.000),TNF-α (r=0.878,P=0.010),APACHE Ⅱ score (r=0.428,P=0.000) in patients with severe sepsis.Significant correlations were also found between IFABP and IL-6 (r=0.812,P=0.000),TNF-α (r

  17. 急性心肌梗死疾病实施心型脂肪酸结合蛋白浓度水平检测意义的探讨%To explore the clinical significance of the early Acute myocardial infarction diagnosis by the Heart-type Fatty Acid-Binding Protein testing

    Institute of Scientific and Technical Information of China (English)

    陈明; 韩帅

    2014-01-01

    Objective To explore the clinical significance of the early Acute myocardial infarction diagnosis by the Heart-type Fatty Acid-Binding Protein testing.Methods Choosing 86 cases of patients with Acute myocardial infarc-tion disease for the experimental group,according to the time we can be divided for the (0-3 h)group of 30 cases,the (3-6 h)group of 28 cases and(≥6 h)group of 28 cases,and 30 cases of healthy check-up for the control group,testing the Heart-type Fatty Acid-Binding Protein and Ischemia Modified Albumin,analyze the results comprehensively.Results Compared with the control group,there were significantly higher of the experimental group of the Heart-type Fatty Acid-Binding Protein and Ischemia Modified Albumin results(P0.05).Clinical specimens correlation analysis results show that the Heart-type Fatty Acid-Binding Protein and the correlation of clinical diagnosis result is good(Kappa=0.81).Conclusion There is a good indicators for the early Acute myocardial infarction diagnosis which as same as to the Ischemia Modified Albumin,and worthy to clin-ical promotion.%目的:探讨检测心型脂肪酸结合蛋白浓度水平对于早期诊断急性心肌梗死疾病的应用价值。方法选择86例确诊为急性心肌梗死的患者设为试验组,根据疾病发作时间可分为(0-3 h)组30例、(3-6 h)组28例和(≥6 h)组28例,并选择同期进行健康体检且结果为健康的人30例设为参照组,所以纳入对象均进行心型脂肪酸结合蛋白浓度水平的检测,同时进行缺血修饰白蛋白浓度水平检测,对结果进行综合分析。结果与参照组比较,(0-3 h)组、(3-6 h)组和(≥6 h)组的患者检测心型脂肪酸结合蛋白浓度水平和缺血修饰白蛋白浓度水平均有显著性升高,差异有统计学意义(P<0.05);阳性检出率分析可见,试验各组的心型脂肪酸结合蛋白和缺血修饰白蛋白的阳性检出率均在80.00%以上且两

  18. The Value of Heart Fatty Acid Binding Protein in Early Diagnosis of Kawasaki Disease with Myocardial Ischemia%心肌脂肪酸结合蛋白在川崎病心肌缺血损伤早期诊断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    段庆宁

    2013-01-01

    目的:探讨心肌脂肪酸结合蛋白(h-FABP)在川崎病患儿心肌缺血损伤早期诊断中的应用价值。方法分别测定54例川崎病患儿在急性期、亚急性期、恢复期的h-FABP,并选择50例健康患儿为对照组。应用SPSS13.0软件对结果进行统计学分析。结果川崎病患儿各期h-FABP水平均明显高于对照组(P<0.05)。结论h-FABP可作为川崎病心肌缺血损伤早期判断指标。%Objective To investigate the value of heart fat y acid binding protein in early diagnosis of kawasaki disease (KD) complicated with myocardial ischemia. Methods Heart fat y acid binding protein (h-FABP) levels were measured in acute stage, subacute stage and recovery stage of KD Patients, and 50 healthy controls as wel .The results were analyzed by statistical package for the social science 13.0 (SPSS 13.0). Results The h-FABP levels of al stages in KD were obviously higher than control group (P<0.05). Conclusion H-FABP can be used in early diagnosis of myocardial ischemia in KD.

  19. Nucleic acid binding and other biomedical properties of artificial oligolysines

    Directory of Open Access Journals (Sweden)

    Roviello GN

    2016-11-01

    Full Text Available Giovanni N Roviello,1 Caterina Vicidomini,1 Vincenzo Costanzo,1 Valentina Roviello2 1CNR Istituto di Biostrutture e Bioimmagini, Via Mezzocannone site and Headquarters, 2Centro Regionale di Competenza (CRdC Tecnologie, Via Nuova Agnano, Napoli, Italy Abstract: In the present study, we report the interaction of an artificial oligolysine (referred to as AOL realized in our laboratory with targets of biomedical importance. These included polyinosinic acid (poly rI and its complex with polycytidylic acid (poly I:C, RNAs with well-known interferon-inducing ability, and double-stranded (ds DNA. The ability of the peptide to bind both single-stranded poly rI and ds poly I:C RNAs emerged from our circular dichroism (CD and ultraviolet (UV studies. In addition, we found that AOL forms complexes with dsDNA, as shown by spectroscopic binding assays and UV thermal denaturation experiments. These findings are encouraging for the possible use of AOL in biomedicine for nucleic acid targeting and oligonucleotide condensation, with the latter being a key step preceding their clinical application. Moreover, we tested the ability of AOL to bind to proteins, using serum albumin as a model protein. We demonstrated the oligolysine–protein binding by CD experiments which suggested that AOL, positively charged under physiological conditions, binds to the protein regions rich in anionic residues. Finally, the morphology characterization of the solid oligolysine, performed by scanning electron microscopy, showed different crystal forms including cubic-shaped crystals confirming the high purity of AOL. Keywords: nucleic acid binding, polyinosinic acid, double-stranded nucleic acids, oligolysine, circular dichroism

  20. Comparative study of the fatty acid binding process of a new FABP from Cherax quadricarinatus by fluorescence intensity, lifetime and anisotropy.

    Directory of Open Access Journals (Sweden)

    Jiayao Li

    Full Text Available Fatty acid-binding proteins (FABPs are small cytosolic proteins, largely distributed in invertebrates and vertebrates, which accomplish uptake and intracellular transport of hydrophobic ligands such as fatty acids. Although long chain fatty acids play multiple crucial roles in cellular functions (structural, energy metabolism, regulation of gene expression, the precise functions of FABPs, especially those of invertebrate species, remain elusive. Here, we have identified and characterized a novel FABP family member, Cq-FABP, from the hepatopancreas of red claw crayfish Cherax quadricarinatus. We report the characterization of fatty acid-binding affinity of Cq-FABP by four different competitive fluorescence-based assays. In the two first approaches, the fluorescent probe 8-Anilino-1-naphthalenesulfonate (ANS, a binder of internal cavities of protein, was used either by directly monitoring its fluorescence emission or by monitoring the fluorescence resonance energy transfer occurring between the single tryptophan residue of Cq-FABP and ANS. The third and the fourth approaches were based on the measurement of the fluorescence emission intensity of the naturally fluorescent cis-parinaric acid probe or the steady-state fluorescence anisotropy measurements of a fluorescently labeled fatty acid (BODIPY-C16, respectively. The four methodologies displayed consistent equilibrium constants for a given fatty acid but were not equivalent in terms of analysis. Indeed, the two first methods were complicated by the existence of non specific binding modes of ANS while BODIPY-C16 and cis-parinaric acid specifically targeted the fatty acid binding site. We found a relationship between the affinity and the length of the carbon chain, with the highest affinity obtained for the shortest fatty acid, suggesting that steric effects primarily influence the interaction of fatty acids in the binding cavity of Cq-FABP. Moreover, our results show that the binding affinities

  1. 阿司匹林及其衍生物与脂肪酸结合蛋白4复合物的晶体学研究%Crystallography study of the complexes of human fatty acid binding protein 4 with aspirin and its derivative

    Institute of Scientific and Technical Information of China (English)

    黄佩; 李敏军; 左刚; 郭豪杰; 周欢; 谢牧云; 郁峰; 徐春艳; 何建华

    2016-01-01

    脂肪酸结合蛋白4(Fatty Acid Binding Protein 4, FABP4)作为脂肪酸伴侣,参与调节脂肪酸代谢、运输、脂介导的信号转导以及巨噬细胞的炎症反应。该蛋白的抑制经常作为治疗脂肪代谢疾病的有效方案。本文报道了经典非甾体抗炎药阿司匹林及其水解物水杨酸与FABP4蛋白复合物的晶体结构,从而推测阿司匹林可能通过FABP4蛋白途径抑制动脉粥样硬化的分子机制。结构分析进一步阐明了FABP4蛋白疏水残基Phe16苯环侧链与水杨酸之间的 C-H-π相互作用比亲水位点静电相互作用提供更稳定的结合。该发现为设计更高选择性FABP4抑制剂提供了新的途径。%Background:Fatty acid binding protein 4 (FABP4), as fatty acid chaperone, plays center roles in lipid transport, lipolysis and liposynthesis, and it has been proved to be involved in the lipid signaling and inflammatory responses. Inhibitors of FABP4 are promising treatments for the diabetes and atherosclerosis. Purpose:The aim is to reveal the structural conformation of aspirin and salicylic acid binding to the FABP4, and to explore the novel structural features for the design of high-selective FABP4 inhibitors. Methods: Single crystal X-ray diffraction is applied to solve the structure of the ligand-protein complexes. Results:We have determined the crystal structures of FABP4 in complex with aspirin and its derivative, and from which a special C-H-πinteraction between the residues Phe16, Arg126 and the benzyl ring of aspirin has been defined. Conclusion:The complex structures of FABP4 bound with aspirin and its derivative show that the edge-to-face C-H-πinteraction between the residues Phe16, Arg126 and the benzyl ring of aspirin is a critical intermolecular force between the ligand-FABP4 interactions, which enables us to consciously apply these interactions in hit and lead optimization in rational structure based drug design.

  2. Crystal structures of the staphylococcal toxin SSL5 in complex with sialyl Lewis X reveal a conserved binding site that shares common features with viral and bacterial sialic acid binding proteins.

    Science.gov (United States)

    Baker, Heather M; Basu, Indira; Chung, Matthew C; Caradoc-Davies, Tom; Fraser, John D; Baker, Edward N

    2007-12-14

    Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared by other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.

  3. Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Baker, H.M.; Basu, I.; Chung, M.C.; Caradoc-Davies, T.; Fraser, J.D.; Baker, E.N.

    2009-06-02

    Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared by other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.

  4. Value of heart-type fatty acid-binding protein to the early diagnosis of acute myocardial infarction%心型脂肪酸结合蛋白在急性心肌梗死早期诊断中价值

    Institute of Scientific and Technical Information of China (English)

    马春华; 王文红; 曲淑杰; 张彦宗; 秦笛

    2012-01-01

    Objective To investigate the value of heart-type fatty acid-binding protein (H-FABP) to the early diagnosis of acute myocardial infarction. Methods A total of 83 patients were suspected acute myocardial infarction at admission in 6 hours after onset of acute chest pain. They were randomly divided into AMI group (n = 32) and non-AMI group (n = 51) including 33 patients with unstable angina pectoris (UAP group) and 18 patients with non-cardiogenic chest pain (NCCP group). Another 40 healthy volunteers were as controls (control group). The plasma level of H-FABP was measured with ELISA, and compared with the traditional cardiac markers. Results The H-FABP level was significantly higher in AMI group than that in the other three groups (P<0. 01). ROC curve showed AUC of H-FABP was 0. 954 (95%CI: 0. 912 to 0. 997). The optimum cut-off point of H-FABP for diagnosing AMI was 6. 65 ng/mL. The sensitivity, specificity, negative prediction value and accuracy of H-FABP for diagnosing AMI in 6 hours were 90. 26%, 80.39%, 93.18% and 84. 34% respectively. The sensitivity, negative prediction value and accuracy of H-FABP were significantly higher than those of the traditional cardiac markers as myoglobin, creatine kinase-myocardial band and cardiac troponin I (P<0. 05). Conclusion H-FABP has better value to diagnosing AMI in the early stage.%目的 探讨血浆心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)对早期诊断急性心肌梗死(acute myocardial infarction,AMI)的意义.方法 发病6h内以急性胸痛就诊的疑似AMI患者83例,根据出院诊断分为AMI组32例与非AMI组51例,非AMI组又分为不稳定型心绞痛33例(UAP组)与非心源性胸痛18例(NCCP组),选择体检健康者40名为对照组,采用ELISA法检测各组血清H-FABP水平,并与传统心肌标志物的诊断效能进行比较.结果 AMI组血清H-FABP水平明显高于非AMI组和对照组(P均<0.01);ROC曲线显示,H-FABP的AUC为0.954(95%CI:0.912~0

  5. Predictive value of heart fatty acid-binding protein to major adverse cardiovascular events in patients with acute myocardial infarction%心型脂肪酸结合蛋白对急性心肌梗死患者主要不良心脏事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    魏庆民; 周彬; 史永堂; 张友良

    2012-01-01

    Objective To observe the predictive value of peak concentration of plasma heart fatty acid-binding protein (H-FABP) to major adverse cardiovascular events ( MACE ) in patients with acute myocardial infarction ( AMI) . Methods The AMI patients ( n=60) were selected within two hours from admission to disease attack from Jan. 2010 to Jim. 2011. The concentration of plasma H-FABP was detected every two hours in the patients from admission to disease attack for 10 hours. According to the average value of H-FABP peak value, all the patients were divided into group A ( with higher H-FABP than average ) and group B ( with lower H-FABP than average ) . The occurrence status of MACE [severe heart failure, malignant arrhythmia, recurrent myocardial infarction, cardiac death and target lesion revascularization ( TLR ) ] was compared between two groups after disease attack for one month and one year. Results After disease attack for one month and one year, the incidence of severe heart failure was higher in group A than that in group B (P<0.05 ) , and the incidence of other events had no statistical difference between two groups. Conclusion The increase of H-FABP peak value has some predictive value to severe heart failure of MACE in AMI patients.%目的 观察血浆心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)的峰值浓度对急性心肌梗死(AMI)患者主要不良心脏事件(MACE)的预测价值.方法 入选2010年1月至2011年6月入院距发病时间2h以内的AMI患者60例,于入院即刻至发病10h期间,每2h测定1次血浆H-FABP的浓度.根据H-FABP峰值水平的平均值将患者划分为H-FABP高值组和低值组,比较两组患者发病后1个月、1年的主要不良心脏事件(严重心力衰竭、恶性心律失常、再发心肌梗死、心源性死亡、靶病变血管重建)的发生率.结果 与H-FABP低值组相比,H-FABP高值组发病后1个月、1年,MACE及严重心力衰竭的发生率更

  6. 心型脂肪酸结合蛋白在心梗患者行介入治疗中的意义%Significance of Heart-type Fatty Acid Binding Protein in Interventional Therapy for Patients With Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    刘伟忠

    2015-01-01

    Objective To study the applications of heart-type fatty acid binding protein in interventional treatment for patients with myocardial infarction, to explore the change of heart-type fatty acid binding protein(H-FABP)in patients with percutaneous coronary intervention(PCI). Methods 178 cases of ST-segment elevation myocardial infarction patients were selected for research and analysis. After coronary intervention in patients with ST fall down as the ST group,the other for non-ST group. For patients with H-FABP and troponin(cTnI)were measured, observed ST decline rate after two hours. Results There was no statistical difference between two groups,H-FABP after six hours was better than before surgery. H-FABP within 24 hours of ST group patients to return to a normal state,non-ST group did not fall back to normal state. Conclusion H-FABP of ST elevation myocardial infarction is directly linked to the severity of coronary artery disease. Surgery will affect the H-FABP levels in patients. The patients of ST fal by more than 50%and H-FABP decreased to normal status,clinical myocardial injury lighter, reperfusion effect was better.%目的:研究分析心型脂肪酸结合蛋白对心梗患者介入治疗的应用情况,探讨患者使用经皮冠脉介入治疗对患者心型脂肪酸结合蛋白变化的影响。方法选取我院178例ST段抬高型心肌梗死患者来进行研究分析,将冠脉介入治疗后ST回落患者作为ST回落组,其余为ST无回落组。对患者的心型脂肪酸结合蛋白以及心肌肌钙蛋白进行测定,观察术后2小时ST回落幅度。结果两组患者术前无统计学差异性,术后6 h的心型脂肪酸结合蛋白均要优于术前。ST回落组患者的心型脂肪酸结合蛋白在24 h内恢复到正常状态,ST无回落组没有恢复正常状态。结论 ST抬高型心肌梗死患者的心型脂肪酸结合蛋白和冠脉病变程度有直接联系,手术会影响患者的心型脂肪酸结合蛋

  7. Value of heart-type fatty acid binding protein to predicting senile unstable angina pectoris%心脏型脂肪酸结合蛋白预测老年不稳定型心绞痛患者预后的价值

    Institute of Scientific and Technical Information of China (English)

    钱海燕; 黄觊; 杨跃进; 杨艳敏; 张朝阳

    2013-01-01

    Objective To explore the value of heart fatty acid binding protein (H-FABP) to predicting the prognosis of senile unstable angina pectoris (UAP).Methods A total of 175 UAP patients aged 60 years or older were divided into positive H-FABP group and negative H-FABP group,and were recorded and analyzed the clinical data and 12-month follow-up survey results.Results The age was older,body mass index was larger,and the proportions of smoking history,family history of coronary heart disease,previous myocardial infarction and coronary artery bypass history,and diabetes mellitus were higher in positive group than those in negative group (P<0.05).The left ventricular ejection fraction was lower in positive group than that in negative group (P<0.05).Coronary angiography results showed that the rates of multi-vessel lesions,diffusive and occlusive lesions,and left main and left anterior descending lesions were higher in positive group than those in negative group (P<0.05).After the follow-up survey for 12 months,the incidence of major adverse cardiovascular events was significantly higher in positive group than that in negative group (P<0.01).Conclusion H FABP is valuable to identify the high risk population and to predict the prognosis of UAP patients aged 60 years or older.%目的 探讨心脏型脂肪酸结合蛋白(heart type fatty acid binding protein,H-FABP)预测老年不稳定型心绞痛患者预后的价值.方法 年龄≥60岁不稳定型心绞痛患者175例,分为H-FABP阳性组48例和阴性组127例,记录并分析2组资料及12个月随访结果.结果 阳性组年龄、体质量指数大于阴性组(P<0.05),吸烟、冠心病家族史、既往心肌梗死病史、冠状动脉介入和旁路移植手术史及合并糖尿病比例明显高于阴性组(P<0.05),左室射血分数低于阴性组(P<0.05);冠状动脉造影显示,阳性组多支、弥漫甚至闭塞病变、累及左主干和前降支比例高于阴性组(P<0.05);随访12个

  8. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs.

    Directory of Open Access Journals (Sweden)

    Zhichao Miao

    2015-12-01

    Full Text Available Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i the definition of nucleic acid binding sites; ii the training and test datasets; iii the algorithmic methods for the prediction strategies; iv the performance measures and v the distribution and availability of the prediction programs. Here we report a large-scale assessment of 19 web servers and 3 stand-alone programs on 41 datasets including more than 5000 proteins derived from 3D structures of protein-nucleic acid complexes. Well-defined binary assessment criteria (specificity, sensitivity, precision, accuracy… are applied. We found that i the tools have been greatly improved over the years; ii some of the approaches suffer from theoretical defects and there is still room for sorting out the essential mechanisms of binding; iii RNA binding and DNA binding appear to follow similar driving forces and iv dataset bias may exist in some methods.

  9. 心型脂肪酸结合蛋白在急性心肌梗死早期诊断中的临床应用%The clinical application of heart-fatty acid binding protein in AMI early diagnosis

    Institute of Scientific and Technical Information of China (English)

    罗俭权; 李竞春; 龙振洪; 徐超成; 江金萍

    2016-01-01

    目的探讨心型脂肪酸结合蛋白(heart-fatty acid binding protein, H-FABP)对早期诊断急性心肌梗死(acute myocardial infarction, AMI)的临床应用价值。方法选取2013年1月至2015年6月我院诊断为AMI的患者151例为AMI组,同期选择有胸痛指征但最终排除AMI诊断的其他疾病患者68例为对照组,检测两组患者发病后0-3 h、3-6 h、6-12 h血清H-FABP、心肌肌钙蛋白I(cardiac tro-ponin I, cTnI)、肌酸激酶(creatine kinase, CK)及肌酸激酶同工酶(MB isoenzyme of creatine kinase, CK-MB)水平,对检测结果进行统计学分析。结果 AMI组0-3 h、3-6 h、6-12 h的H-FABP、cTnI、CK、CK-MB检测水平均显著高于对照组,且差异均具有统计学意义(P均<0.05)。血清H-FABP诊断AMI的灵敏度、特异性及受试者工作特征曲线下面积分别为78.8%、89.7%及0.919,均高于其他三项指标。所有AMI患者中,H-FABP与cTnI、CK及CK-MB在不同时间段的检测结果均有较好的相关性,且相关系数r均>0.8。结论 H-FABP对早期诊断AMI有较好的临床应用价值,优于cTnI、CK及CK-MB。%Objective To investigate the clinical application value of heart-fatty acid binding protein (H-FABP) in acute myocardial infarction(AMI) diagnosis. Methods 151 cases AMI patients in our hospital from January 2013 to June 2015 were collected as the AMI group. 68 cases patients with chest pain indications but obviated AMI during the same period were selected as the control group. The levels of H-FABP , cardiac troponin I(cTnI), creatine kinase(CK) and MB isoenzyme of creatine kinase(CK-MB) at 0-3 h, 3-6 h, 6-12 h of all the patients to fall in disease were detected. The results were analyzed statistically. Results The levels of H-FABP, cTnI, CK and CK-MB at 0-3 h, 3-6 h, 6-12 h in AMI group were all higher than that of control group, and the differences all had statistical significance

  10. 慢性心力衰竭患者心型脂肪酸结合蛋白与超敏C-反应蛋白的变化及其相关性%The relationship of heart-type fatty acid binding protein and high-sensitivity C-reactive protein in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    李洁琪; 李晓翔; 吴立荣; 方颖; 李屏

    2009-01-01

    Objective To examine clinical significance and relativity of heart-type fatty acid binding protein (H-FABP) and high-sensitivity C-reactive protein (hs-CRP) in patients with chronic heart failure. Methods Ser-um concentrations of H-FABP and hs-CRP were measured in 60 patients with chronic heart failure and 30 control subjects. Left ventricular ejection fraction (LVEF) was examined by Doppler echocardio graphic in all subjects. Re-sults Serum concentrations of H-FABP and hs-CRP were higher in patients with chronic heart failure than in con-trol subjects[(6.11±1.49)μg/L vs (4.24±1.40)μg/L,and (12.77±3.65)mg/L vs(4.85±1.35) mg/L,t=5.746 and 7.543,P<0.01] but LVEF was lower in patients with chronic heart failure than in control subjects [(42.13±6.55) % vs (61.50±3.89) %,t=-14.902,P<0.01]. In CHF subgroups,H-FABP and hs-CRP lev-el increased with advancing NYHA class (F=26.288 and 351.784,P<0.01) but LVEF decreased (F=252.834,P<0.01). The serum H-FABP concentrations had a positive correlation with serum hs-CRP concentrations (r=0.801,P<0.01),and a negative correlation with LVEF (r=-0.718,P<0.01) ;serum hs-CRP concentrations had a negative correlation with LVEF(r=-0.881,P<0.01). Conclusion Serum H-FABP and hs-CRP levels are in-creased with the worsening of CHF. H-FABP and hs-CRP level are pnsitiviely related. The quantitative determination of serum concentrations of H-FABP and hs-CRP is valuable for risk stratification in patients with chronic heart fail-ure.%目的 观察慢性心力衰竭(CHF)患者血清心型脂肪酸结合蛋白(H-FABP)和超敏C-反应蛋白(hs-CRP)的浓度变化,并探讨其相关性及临床意义.方法 选择不同心功能级别的CHF患者60例及同期健康体检者30例,测定其血清H-FABP及hs-CRP的浓度,同时用彩色多普勒超声测定左心室射血分数(LVEF).结果 CHF组H-FABP[(6.11±1.49)μg/L]及ks-CRP[(12.77±3.65)mg/L]的浓度均较对照组[分别为(4.24±1.40)μg/L和(4.85±1.35)mg/L]升高(t值分别为5

  11. Cloning of a DNA-binding protein that interacts with the ethylene-responsive enhancer element of the carnation GST1 gene.

    Science.gov (United States)

    Maxson, J M; Woodson, W R

    1996-07-01

    Ethylene transcriptionally activates a glutathione S-transferase gene (GST1) at the onset of the senescence program in carnation (Dianthus caryophyllus L.) flower petals. A 126 bp region of the GST1 promoter sequence has been identified as an ethylene-responsive enhancer element (ERE). In this paper, we demonstrate the ability of nuclear proteins from senescing petals to recognize a 22 bp sequence within the ERE (ERE oligonucleotide). Mutation of the ERE oligonucleotide sequence significantly alters the strength of this nuclear protein-DNA association. The wild-type ERE oligonucleotide sequence was used to isolate a cDNA clone encoding a sequence-specific DNA binding protein. Nucleotide sequencing and deduced amino acid sequence analysis of this cDNA predicted a 32 kDa protein which we have designated carnation ethylene-responsive element-binding protein-1 (CEBP-1). The mRNA expression pattern of CEBP-1 suggests that it is not transcriptionally regulated by ethylene. The amino acid sequence homology of CEBP-1 with other plant nucleic acid binding proteins indicates a conserved nucleic acid binding domain. Within this domain are two highly conserved RNA-binding motifs, RNP-1 and RNP-2. An acidic region and a putative nuclear localization signal are also identified.

  12. Role of heart-type fatty acid-binding protein in assessing the prognosis of acute pulmonary embolism%心肌型脂肪酸结合蛋白在急性肺栓塞预后中的作用

    Institute of Scientific and Technical Information of China (English)

    李宾公; 郑泽琪; 王梦洪; 彭景添; 颜琼; 肖坚

    2011-01-01

    Objective To study the role of heart - type fatty acid - binding protein ( H - FABP) in assessing the prognosis of acute pulmonary embolism (APE).Methods The levels of plasma H - FABP, cTnI and D - dimer were determined in 72 patients with APE and 30 healthy controls.The associations between the biomarkers and severe complications were determined by Logistic regression model.Results The levels of D - dimer in the patients with APE were significantly higher than that in healthy controls (P < 0.01).The incidence of severe complications was higher in the H FABP positive group of APE than in the H - FABP negative group (66.7% vs 3.5%, P < 0.05).By Logistic regression analysis, elevated H -FABP was associated with a 50.44 -fold increase in the death or complication risk (95% CI 7.40 ~ 342.38, P < 0.001).Conclusion The H - FABP might be a useful biomarker for prediction prognosis of patients with APE.%目的 探讨心肌型脂肪酸结合蛋白(H-FABP)在急性肺栓塞(APE)预后中的作用.方法 检测72例确诊为急性肺栓塞(APE)患者及对照组30例健康受试者血浆H-FABP、心肌肌钙蛋白I(cTnI)、D-二聚体水平.应用Logistic回归模型分析各生化标志物与APE预后的关系.结果 APE组血浆D-二聚体水平较对照组明显增高(P<0.01).APE组中H-FABP阳性组30 d内不良事件发生率高于H-FABP阴性组(66.7% vs 3.5%,P<0.05).Logistic回归分析显示,H-FABP为APE预后的独立危险因素,H-FABP阳性者发生不良事件的危险性是H-FABP阴性者的50.44倍(95%CI 7.40~342.38,P<0.001).结论 H-FABP阳性APE者预后较差,H-FABP可用于APE的危险分层.

  13. The changes and clinical significance of heart fatty acid-binding protein concentrations in children patients after open heart surgery%儿童心脏直视术后心肌脂肪酸结合蛋白水平的变化及意义

    Institute of Scientific and Technical Information of China (English)

    王永连; 王忠民; 陈志军; 姚文健; 卢建国; 李汉臣

    2009-01-01

    Objective To observe the changes and clinical significance of plasma heart fatty acid-binding protein(H-FABP)in children after open heart surgery. Methods Forty patients with congenital heart disease(CHD) who had undergone cardiac operation with cardiopulmonary bypass(CPB) were selected in this study,and were randomly divided into two groups (each 20 cases): cold crystalloid cardioplegia perfusion group (Ⅰ group) and cold blood cardioplegia perfusion group(Ⅱ group). Blood samples were taken to check the plasma H-FABP concentration before CPB and different time after CPB. Plasma H-FABP concentration was estimated by enzyme-linked immunosorbent assay (ELISA). Results The difference of plasma concentration of H-FABP before operation was not obvious between Ⅰ group and Ⅱ group. The plas-ma concentration of H-FABP intraoperation and different time after operation was higher than that before anesthesia induction obviously in two groups, and Ⅰ group rose more significantly [(50.13±3.98) μg/L vs (39.27±4.22) μg/L, P0.05),体外循环结束即刻,1、4、12、24 hH-FABP水平较麻醉诱导前均有不同程度的升高(P<0.01),于体外循环结束后1 h达峰值(P<0.01),Ⅰ组升高比Ⅱ组更明显[(50.13±3.98)μg/L比(39.27±4.22)μg/L,P<0.01].结论 体外循环心脏术后H-FABP显著升高,峰值浓度出现早,可作为一项早期判断心肌损伤的敏感指标.与灌注晶体停搏液相比,含血停搏液有良好的心肌保护作用.

  14. 心肌脂肪酸结合蛋白对急性冠脉综合征患者病情转归的预测价值%The value of heart-type fatty acid-binding protein in predicting disease outcome of patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    谢明水; 刘杨; 蒋守涛; 李玲; 晏文强; 张振建

    2013-01-01

    OBJECTIVE To investigate the value of heart-type fatty acid-binding protein in predicting disease outcome of patients with acute coronary syndrome (ACS). METHODS The H-FABP levels of 81 patients with acute coronary syndrome were detected. In 30 cases of acute myocardial infarction (AMI), there were 26 cases of unstable angina pectoris (UAP), 25 cases of stable angina pectoris (SAP). At the same period, 27 healthy volunteers were selected as the control group. The disease outcome of various types of ACS were analyzed and compared. RESULTS The H-FABP level (73.35 ± 56.73ngml) in AMI group was highest, and the H-FABP level (13.50 ± 5.64ng/ml) in UAP group was higher (P 0.05). Compared with all groups, the H-FABP level of AMI group was highest, but the disease outcome and prognosis were the worst (P < 0.05). CONCLUSION The H-FABP level could be used as an effective predictive indicator in disease outcome of patients with acute coronary syndrome.%目的 探讨心肌脂肪酸结合蛋白对急性冠脉综合征患者病情转归的预测价值.方法 81例急性冠脉综合征患者检测血浆心肌脂肪酸结合蛋白表达水平,其中急性心肌梗死(AMI) 30例,不稳定型心绞痛(UAP) 26例,稳定型心绞痛(SAP) 25例,同期选择27例健康体检者为对照组.对各组疾病患者病情转归进行分析比较.结果 AMI组的H-FABP水平(73.35±56.73 ng/ml)最高,UAP组(13.50±5.64 ng/ml)次之(P< 0.01); SAP组(4.65±3.38 ng/ml)与对照组(3.42±1.53 ng/ml)比较差异无统计学意义(P>0.05);各组观察对比,H-FABP水平最高的AMI组病情转归及预后最差(P<0.05).结论 H-FABP可作为一种预测急性冠脉综合征患者病情转归情况的有效指标.

  15. The research progress on the diagnosis of myocardial injury of heart-type fatty acid-binding protein%心型脂肪酸结合蛋白在心肌损伤诊断中的研究进展

    Institute of Scientific and Technical Information of China (English)

    李继元; 李洪; 杨天德

    2011-01-01

    背景 心肌标志物的正确应用为临床准确诊断、鉴别心血管疾病和判断治疗效果起到了革命性的作用,目前已经有越来越多的心肌损伤标志物在临床中得到应用,现对心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)的研究相关进展作一综述.目的 了解H-FABP的理化性质和临床检测方法,认识H-FABP在早期心肌梗塞诊断中的独特优势.内容 结合国内外文献对H-FABP的基础和临床研究现状进行了阐述,对目前临床检测的方法进行了介绍,并对发展的趋势做了进一步展望.趋向 随着H-FABP测定方法的不断改进及临床研究的不断深入,H-FABP正逐渐成为诊断心肌损伤的重要生化标志物.%Background The correct application of cardiac markers have played a revolutionary role for clinical accurate diagnosis,identification and treatment of cardiovascular disease. Now more and more cardiac biochemical markers have been applied in clinic researches,and the latest research progress in the field of H-FABP is reviewed in this paper.Objective To understand the physical and chemical properties and clinical detection methods of H-FABP,to recognize the unique advantages in diagnosis of the early AMI.Content To survey the basic and clinical research of H-FABP by reviewing domestic and international literatures, and to introduce the current clinical detection methods.Trend With the development of H-FABP determination methods and clinical research,H-FABP is becoming an important biochemical marker of myocardial injury.

  16. 急性ST段抬高型心肌梗死患者心型脂肪酸结合蛋白水平与GRACE危险评分的相关性研究%Relationship between Heart-type Fatty Acid-binding Protein and GRACE Risk Score in Patients with Acute ST-elevation Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    魏庆民; 周彬; 王晓纲; 樊延明; 王爱平; 刘翠华

    2013-01-01

    Objective To study the relationship between heart - type fatty acid - binding protein ( H - FABP ) level and Global Registry of Acute Coronary Events ( GRACE ) risk score in patients with acute ST - elevation myocardial infarction ( STEMI ). Methods From April 2010 to December 2011 , 60 STEM patients admitted to our hospital within 2 hours of symptom onset were enrolled in this study. Twelve hours after admission, blood samples were obtained for H - FABP measurement every two hours. Then, H - FABP peak values were found. The baseline data were recorded and the GRACE risk score were calculated. The Pearson's correlation analysis were used to analyze the relationship between the H - FABP peak value and GRACE risk score. Results The peak value of H - FABP was ( 59. 4 ± 23. 1 ) μg/L, which occmed 4~8 hours after admission. It was positively correlated with GRACE risk score in these patients ( r = 0.701 , P<0. 05 ). Conclusion H -FABP peak value is directly relevant with GRACE risk score in STEMI patients. Measurement of H - FABP level can provide additional risk stratification information in these patients.%目的 探讨急性ST段抬高型心肌梗死(STEMI)患者血浆心型脂肪酸结合蛋白(H-FABP)的峰值水平与全球急性冠状动脉事件注册(GRACE)风险评分的相关性.方法 选择2010年4月-2011年12月我科收治的发病2 h内的STEMI患者60例,于患者发病后2、4、6、8、10、12 h采血,检测H-FABP水平,找出其峰值.记录患者的基线资料,计算GRACE风险评分,对GRACE评分和H-FABP的峰值水平进行Pearson直线相关分析.结果 H-FABP的达峰时间为4~8 h,平均峰值为(59.4±23.1)μg/L;STEMI患者H-FABP峰值水平与GRACE危险评分呈正相关(r=0.701,P<0.05).结论 STEMI的H-FABP峰值水平与GRACE评分相关,检测H-FABP峰值水平可以为STEMI患者的危险分层提供参考.

  17. Difference of heart fatty acid binding protein in acute ischemic stroke and heamorrhage stroke and its significance%急性脑梗死和脑出血患者心型脂肪酸结合蛋白表达差异及临床意义

    Institute of Scientific and Technical Information of China (English)

    贺桂女; 韩雄; 马勇

    2016-01-01

    目的 探讨血清心型脂肪酸结合蛋白(heart fatty acid binding protein,H-FABP)在急性脑梗死(acute ischemic stroke,AIS)和脑出血(intraeerebral hemorrhage,ICH)患者中的表达差异,分析其与病理特征间的关系.方法 发病12h内AIS患者89例(AIS组)和ICH患者66例(ICH组),采用双抗体夹心ELISA法检测2组血清H-FABP水平,分析血清H-FABP水平与梗死部位、梗死灶大小和梗死病因分型间的关系.结果 AIS组血清H-FABP水平[132.14(81.63,324.26)ng/L]与ICH组[171.35(102.86,382.65)ng/L]比较差异无统计学意义(P>0.05);AIS组和ICH组血清H-FABP水平与初始NIHSS评分均无明显相关性(r=-0.110,P=0.307;r=0.094,P=0.451);AIS组血清H-FABP水平在梗死灶大小和梗死部位上差异无统计学意义(P>0.05);心源性脑梗死患者血清H-FABP水平[263.65(126.32,627.17)ng/L]高于动脉硬化性脑梗死[115.36(82.14,232.48) ng/L]、小血管性梗死[123.06(74.95,288.82)ng/L]和其他病因梗死患者[130.43(59.88,268.10)ng/L](P<0.05).结论 血清H-FABP水平不能鉴别AIS和ICH,可能是预测心源性脑梗死的潜在分子标志物.

  18. Designing genes for successful protein expression.

    Science.gov (United States)

    Welch, Mark; Villalobos, Alan; Gustafsson, Claes; Minshull, Jeremy

    2011-01-01

    DNA sequences are now far more readily available in silico than as physical DNA. De novo gene synthesis is an increasingly cost-effective method for building genetic constructs, and effectively removes the constraint of basing constructs on extant sequences. This allows scientists and engineers to experimentally test their hypotheses relating sequence to function. Molecular biologists, and now synthetic biologists, are characterizing and cataloging genetic elements with specific functions, aiming to combine them to perform complex functions. However, the most common purpose of synthetic genes is for the expression of an encoded protein. The huge number of different proteins makes it impossible to characterize and catalog each functional gene. Instead, it is necessary to abstract design principles from experimental data: data that can be generated by making predictions followed by synthesizing sequences to test those predictions. Because of the degeneracy of the genetic code, design of gene sequences to encode proteins is a high-dimensional problem, so there is no single simple formula to guarantee success. Nevertheless, there are several straightforward steps that can be taken to greatly increase the probability that a designed sequence will result in expression of the encoded protein. In this chapter, we discuss gene sequence parameters that are important for protein expression. We also describe algorithms for optimizing these parameters, and troubleshooting procedures that can be helpful when initial attempts fail. Finally, we show how many of these methods can be accomplished using the synthetic biology software tool Gene Designer.

  19. Study on the relationship of urinary liver-type fatty-acid binding protein and progression of nephropathy in diabetic patients%尿肝型脂肪酸结合蛋白与糖尿病肾病进展的关系研究

    Institute of Scientific and Technical Information of China (English)

    曾学辉; 李忠新; 张春雷; 宋林立

    2014-01-01

    Objective To investigate the relationship of urinary liver-type fatty-acid binding protein and progression of ne-phropathy in diabetic patients .Methods A total of 132 cases of type 1 and type 2 diabetic patients were recruited in this study , and were divided into four groups based on the urine albumin /creatinine and serum creatinine levels , including normal albuminuria group ( n =45), microalbuminuria group ( n =36), clinical albuminuria group ( n =30), and renal failure group ( n =21), Additional 65 healthy subjects were recruited as control group .The levels of urinary liver-type fatty-acid binding protein ( L-FABP) were measured with enzyme-linked immunosorbent assay (ELISA), and serum creatinine, urine creatinine, Liver function, hemoglobin, glycated he-moglobin (HbA1c), albumin (Alb), and 24h urinary protein were measured by respective biochemical or immunological methods . Results With the progression of diabetic nephropathy , the level of urinary L-FABP was gradually increased ( P 0.05).Conclusions The uri-nary L-FABP level can predict the occurrence of early diabetic nephropathy , and also monitor the progression of diabetic nephropathy .%目的:探讨尿肝型脂肪酸结合蛋白( L-FABP)与糖尿病肾病进展的关系。方法选择1型和2型糖尿病患者132例,依据尿蛋白/肌酐比(ACR)和血清肌酐水平分为正常蛋白尿组(45例),微量蛋白尿组(36例),临床白蛋白尿组(30例),肾功能衰竭组(21例),以65例健康体检者为对照组,酶联免疫吸附法( ELISA )测定尿L-FABP含量,同时检测血肌酐(Scr)、尿肌酐、肝功能、血红蛋白、糖化血红蛋白(HbA1c)、白蛋白(Alb)、24 h尿蛋白量、尿白蛋白等指标。结果随着糖尿病肾病的进展,尿L-FABP水平逐渐增高(各组间比较P <0.01),亚组分析显示正常白蛋白组尿L-FABP水平高于健康组( P<0.05),微量白蛋白组尿L-FABP水

  20. The human protein disulfide isomerase gene family

    Directory of Open Access Journals (Sweden)

    Galligan James J

    2012-07-01

    Full Text Available Abstract Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs. These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX. As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR. Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

  1. Molecular evolution of Drosophila cuticular protein genes.

    Directory of Open Access Journals (Sweden)

    R Scott Cornman

    Full Text Available Several multigene families have been described that together encode scores of structural cuticular proteins in Drosophila, although the functional significance of this diversity remains to be explored. Here I investigate the evolutionary histories of several multigene families (CPR, Tweedle, CPLCG, and CPF/CPFL that vary in age, size, and sequence complexity, using sequenced Drosophila genomes and mosquito outgroups. My objective is to describe the rates and mechanisms of 'cuticle-ome' divergence, in order to identify conserved and rapidly evolving elements. I also investigate potential examples of interlocus gene conversion and concerted evolution within these families during Drosophila evolution. The absolute rate of change in gene number (per million years is an order of magnitude lower for cuticular protein families within Drosophila than it is among Drosophila and the two mosquito taxa, implying that major transitions in the cuticle proteome have occurred at higher taxonomic levels. Several hotspots of intergenic conversion and/or gene turnover were identified, e.g. some gene pairs have independently undergone intergenic conversion within different lineages. Some gene conversion hotspots were characterized by conversion tracts initiating near nucleotide repeats within coding regions, and similar repeats were found within concertedly evolving cuticular protein genes in Anopheles gambiae. Rates of amino-acid substitution were generally severalfold higher along the branch connecting the Sophophora and Drosophila species groups, and 13 genes have Ka/Ks significantly greater than one along this branch, indicating adaptive divergence. Insect cuticular proteins appear to be a source of adaptive evolution within genera and, at higher taxonomic levels, subject to periods of gene-family expansion and contraction followed by quiescence. However, this relative stasis is belied by hotspots of molecular evolution, particularly concerted evolution, during

  2. Relationship between serum concentration of heart-type fatty acid binding protein and severity of coronary artery lesion in patients with acute coronary syndrome%心型脂肪酸结合蛋白与急性冠脉综合征患者冠状动脉病变程度的关系

    Institute of Scientific and Technical Information of China (English)

    王亚蓉; 郭壮波; 黄丽萍; 徐元杰

    2013-01-01

    目的 探讨心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)与近期发作急性冠脉综合征患者的冠状动脉病变严重程度的相关性及原因分析.方法 入选暨南大学医学院附属第四医院急性冠脉综合征(发作12h内)患者168例,其中急性心肌梗死86例、不稳定型心绞痛82例.采用双抗体夹心酶联免疫吸附试验(ELISA)法检测血清H-FABP、肌钙蛋白(cardiac troponin T,CTnT)及肌酸磷酸激酶同工酶(creatine phosphokinase isoenzyme,CK-MB)浓度.采用Gensini积分系统对冠状动脉血管病变狭窄程度、病变部位及范围进行定量评定.比较急性心肌梗死组与不稳定型心绞痛组血清H-FABP浓度及冠状动脉病变Gensini积分;比较Gensini积分、冠状动脉狭窄程度、病变支数亚组之间H-FABP浓度;采用直线回归分析方法分析血清H-FABP浓度与冠状动脉病变严重程度、血清cTnT浓度、血清CK-MB浓度的相关性.结果 急性心肌梗死组血清H-FABP浓度显著高于不稳定型心绞痛组,差异有统计学意义[(88.5±32.9)pg/mL vs.(14.3±5.4)pg/mL,P<0.01].随着冠状动脉狭窄程度加重、累及支数增加及Gensini积分增加,血清H-FABP浓度显著升高,差异有统计学意义(P<0.05).血清H-FABP浓度与cTnT (r=0.627,P<0.05)及CK-MB (r=0.530,P<0.05)具有相关性;与患者冠状动脉病变严重程度呈正相关(r=0.538,P<0.01),其相关系数高于cTnT与冠状动脉病变严重程度的相关性(r=0.385,P<0.05).结论 血清H-FABP浓度升高反映了冠状动脉病变严重程度,临床可根据血清H-FABP浓度升高推断冠状动脉病变的严重程度,并采取积极的治疗措施.%Objectives To study the correlation between serum concentration of heart-type fatty acid binding protein (HFABP) and severity of coronary artery lesion in patients with acute coronary syndrome.Methods Serum concentrations of H-FABP,cardiac troponin T (cTnT) and creatine phosphokinase

  3. 心脏脂肪酸结合蛋白对冠状动脉搭桥术后心肌损伤的诊断价值%The diagnosis value of heart fatty acid binding protein for myocardial injury in patients after coronary artery bypass graft

    Institute of Scientific and Technical Information of China (English)

    张兰; 宋丹; 苏晞; 陈国洪; 王琳; 陈运清

    2011-01-01

    目的:探讨心脏脂肪酸结合蛋白(H-FABP)对冠状动脉(冠脉)搭桥术(CABG)患者术后心肌损伤的诊断价值.方法:分别在术前、术中解除主动脉十字夹钳即再灌注即刻、30 min、60 min、90 min、2 h、3 h、4 h、5 h、6 h、12 h、24 h采取动脉血检测H-FABP、肌酸激酶同工酶(CK-MB)、肌钙蛋蛋白I(cTnI).共连续检测了50例.按临床表现分为心肌损伤组和对照组.结果:①对照组(40例)的H-FABP、CK-MB、cTnI在手术前后均没有明显变化.②在心肌损伤组中(10例),在手术前血清H-FABP值为(3.56±1.2)μg/L,在术后(0.85±0.2)h血清H-FABP开始升高并达到峰值(72.4±18.1)μg/L,比CK-MB和cTnI均明显提前(P<0.0001);血清CK-MB值于(4.9±0.6)h开始升高,于(5.9±0.2)h到达峰值(64.4±17.6)IU/L;cTnI值于6 h开始升高,于(13.8±5.7)h达峰值(11.6±4.6)μg/L;再灌注即刻的H-FABP值和H-FABP的峰值呈显著正相关(r=0.88,P<0.0001);H-FABP的峰值分别与CK-MB峰值、cTnI亦呈显著正相关(r=0.91,P<0.0001和r=0.87,P<0.0001).结论:CABG术后监测H-FABP能早期发现心肌损害,并能预示心肌损害的程度,H-FABP是极具前途的血清心脏标记物之一.%Objective:To investigate the diagnosis value of heart fatty acid binding protein for myocardial injury in patients after coronary artery bypass graft (CABG).Method:Serum level of creatine kinase-MB (CK-MB), troponin-Ⅰ (cTnI), and human heart fatty acid binding protein (H-FABP) were detected in continued patients being undergone CABG at before operation,and the time interval reperfusion at 0 min, 30 min, 60 min, 90 min, 2 hr, 3 hr, 4 hr, 5 hr, 6 hr, 12 hr, 24 hr, respectively.Patients were divided into two groups (myocardial injury group and control group) according to the clinic characteristic information.Result:In the control group, the serum levels of H-FABP, CK-MB and cTnI did not change before and after CABG.In the myocardial injury group, the serum levels of H-FABP, CK-MB and c

  4. The Correlation Between Serum Liver-type Fatty Acid Binding Protein and non-Alcoholic Fatty Liver Extent and its Clinical Indexes%血清肝型脂肪酸结合蛋白与非酒精性脂肪肝病程度及相关临床指标的关联及其意义

    Institute of Scientific and Technical Information of China (English)

    刘晓军; 杜亚奇; 刘东屏

    2012-01-01

    Objective To investigate the correlation of serum liver-type fatty acid binding protein( L-FABP) and degree of fatty liver and its clinical parameters in nonalcoholic fatty liver (NAFLD) patients. Methods 60 cases of NAFLD and 60 cases of healthy controls were selected. The levels of serum L- FABP( g/L) and blood biochemical indexes were measured by ELJSA. In addition,we calculated body mass index(BMI) ,waist to hip ratio(WHR)and homeostasis model assessment insulin resistance index( HOMA-IR). Results In the NAFLD group serum L-FABP was obviously higher( 19.35 ±6.55 vs 15.31 ± 2.49) ,and ALT,TG,FBC,BMI,WHR were also markedly higher compared with the control group,while the difference was statistically significant( P 0.05). Correlation test results suggested L-FABP level was positively related with ALT (r =0. 624,p0. 05,moderate vs severe( 18. 37 ±3. 80 vs 25.03 ±5.26) (g/L) P< 0.05, compared with the healthy control group(15.31 ±2.49) (g/L) , only severe fatty liver group, but not other groups, had significant difference. Conclusion Serum L-FABP level of severe NAFLD patients was significantly increased,and L-FABP level was related with biochemical parameters of liver function.%目的 探讨非酒精性脂肪肝(non- alcoholic- fatty liver disease,NAFLD)患者血清肝型脂肪酸结合蛋白(liver-type fatty acid binding protein,L-FABP)与脂肪肝程度及相关临床指标的关系及其意义.方法 入选NAFLD 60例,健康对照60例.ELISA法测定血清L-FABP(g/L)及血生化指标,同时计算体重指数(BMl),腰臀比(WHR)及稳态模型评估胰岛素抵抗指数(HOMA-IR),B超判定脂肪肝程度.结果 NAFLD组与对照组相比,血清L-FABP明显增高,( 19.35 ±6.55 vs 15.31±2.49).NAFLD组ALT、TG、FBG,BMI、WHR水平明显高于对照组,差异显著(P<0.05),TC、AST、GGT两组间差异无统计学意义(P>0.05).相关性检测结果L-FABP水平与ALT(r=0.624,P<0.05)、TG(r=0.617,P<0.05)、FBG(r =0.579,P<0.05)、WHR(r =0.692,P <0

  5. Coevolution of gene expression among interacting proteins

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Hirsh, Aaron E.; Wall, Dennis P.; Eisen,Michael B.

    2004-03-01

    Physically interacting proteins or parts of proteins are expected to evolve in a coordinated manner that preserves proper interactions. Such coevolution at the amino acid-sequence level is well documented and has been used to predict interacting proteins, domains, and amino acids. Interacting proteins are also often precisely coexpressed with one another, presumably to maintain proper stoichiometry among interacting components. Here, we show that the expression levels of physically interacting proteins coevolve. We estimate average expression levels of genes from four closely related fungi of the genus Saccharomyces using the codon adaptation index and show that expression levels of interacting proteins exhibit coordinated changes in these different species. We find that this coevolution of expression is a more powerful predictor of physical interaction than is coevolution of amino acid sequence. These results demonstrate previously uncharacterized coevolution of gene expression, adding a different dimension to the study of the coevolution of interacting proteins and underscoring the importance of maintaining coexpression of interacting proteins over evolutionary time. Our results also suggest that expression coevolution can be used for computational prediction of protein protein interactions.

  6. Porcine lung surfactant protein B gene (SFTPB)

    DEFF Research Database (Denmark)

    Cirera Salicio, Susanna; Fredholm, Merete

    2008-01-01

    The porcine surfactant protein B (SFTPB) is a single copy gene on chromosome 3. Three different cDNAs for the SFTPB have been isolated and sequenced. Nucleotide sequence comparison revealed six nonsynonymous single nucleotide polymorphisms (SNPs), four synonymous SNPs and an in-frame deletion of 69...... bp in the region coding for the active protein. Northern analysis showed lung-specific expression of three different isoforms of the SFTPB transcript. The expression level for the SFTPB gene is low in 50 days-old fetus and it increases during lung development. Quantitative real-time polymerase chain...

  7. The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.

    Directory of Open Access Journals (Sweden)

    Nancy A Stearns

    Full Text Available Antibodies to DNA (anti-DNA are the serological hallmark of systemic lupus erythematosus (SLE and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3, hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.

  8. Diagnostic Value of Heart Fatty Acid-Binding Protein among Early Acute Coronary Syndrome Patients%心肌脂肪酸结合蛋白对急性冠脉综合征患者的早期诊断价值

    Institute of Scientific and Technical Information of China (English)

    陈可; 王春明; 刘海波; 刘艳红; 鲍迎春; 方裕; 张丽梅; 赵乾磊

    2011-01-01

    Objective To determine the value of heart fatty acid - binding protein ( H - FABP ) in early diagnosis of acute coronary syndrome ( ACS ). Methods Serum concentrations of H - FABP were measured in 172 consecutive patients hospitalized for ACS within 6 h of the onset of chest pain. Of these patients, 96 were with established AMI and 76 were with unstable angina pectoris. Still, 74 normal healthy subjects matched for age and sex were enrolled as controls. Results Levels of HFABP in the AMI group and the UA group were ( 82.2±96.6 ) μg/L and ( 7.9±5.1 ) μg/L, significantly higher than those in controls [ ( 4.2 ± 1.8 ) μg/L ] ( P < 0.01 ). Area under the curve for receiver operating characteristic curve ( ROC ) of HFABP - diagnosed AMI was 0.952 [ 95% CI ( 0.919, 0.984 ) ], and the correspondence value for UA was 0.787 [ 95% CI ( 0.714,0.859 ) ]. Diagnostic sensitivity and specificity of H - FABP were 81.5% and 97.3% for AMI when cut - off value was defined as 7.47μg/L; diagnostic sensitivity and specificity for UA were 71.1% and 71.6% when cut - off value was defined as 5.20 μg/L. Conclusion Serum levels of H - FABP can serve as an early diagnostic index for myocardial necrosis or damage ,and could be applied to the early diagnosis of acute coronary syndrome.%目的 探讨血浆心肌脂肪酸结合蛋白(H-FABP)对急性冠脉综合征(ACS)的诊断价值.方法 对172例连续入选的ACS住院患者出现胸痛6 h内测定血浆H-FABP水平,其中急性心肌梗死(AMI)组96 例,不稳定性心绞痛(UA)组76例;并选择74例健康体检正常者为对照组.结果 AMI组、UA组的H-FABP水平分别为(82.2±96.6)μg/L、(7.9±5.1)μg/L,与对照组(4.2±1.8)μg/L比较,差异均有统计学意义(P<0.01).H-FABP诊断AMI的受试者工作特征(ROC)曲线下面积为0.952[95%CI(0.919,0.984)];而诊断UA的ROC曲线下面积为0.787[95%CI(0.714,0.859)];以7.47 μg/L作为H-FABP早期诊断AMI的最佳临界值,其敏感性为81.5%,

  9. Changes and clinical value of heart-type fatty acid binding protein in patients with acute hypertensive cerebral hemorrhage%急性高血压脑出血患者血清h-FABP水平变化及其临床应用价值

    Institute of Scientific and Technical Information of China (English)

    杨文东

    2012-01-01

    目的 通过观察急性高血压脑出血患者血清心脏型脂肪酸结合蛋白(h-FABP)水平变化,探讨其临床检测价值.方法 血清h-FABP采用双抗体夹心酶联免疫一步法定量检测;cTnI采用固相酶联免疫吸附实验(ELISA);CK-MB采用免疫抑制法测定HT5"H〗结果 急性高血压脑出血患者组血清h-FABP水平显著高于对照组(P<0.01),大量出血者及意识不清者血清h-FABP水平分别显著高于小量出血者及意识清醒者(P<0.01);血清h-FABP阳性率显著高于血清cTnI、CK-MB及心电图的阳性率(P<0.01);死亡率为25.5%(28/110),血清h-FABP、cTnI、CK-MB及心电图异常组的死亡率显著高于正常组(P<0.01);血清h-FABP预测发生死亡具有高的敏感性和阴性预测值,特异性和准确度较低,但心电图具有较高的特异性(64.5%)和准确度(69.1%).结论 血清h-FABP定量测定可作为判断急性高血压脑出血病情轻重及评价发生意外的1项客观指标,联合心电图监测临床价值更高.%Objective To understand the clinical value of heart-type fatty acid binding protein (h-FABP) in patients with acute hypertensive cerebral hemorrhage(AHCE) through the variation analysis of its serum level. Methods Serum level of h-FABP was determined by enzyme-linked immunosorbent one-step quantitative detection, cardiac troponin I(cTnl) was detected by solid-phase enzyme-linked immunosorbent assay (ELISA) and isoenzyme MB of creatine kinase(CK-MB) was assayed by immunosuppression assay. Results The h-FABP level in(AHCE) group was significantly higher than healthy control group(P<0. 01) and that in AHCE patients with massive haemorrhage and unconsciousness was significantly higher than in patients with small heamorrhage and consciousness. The positive rate of h-FABP was significantly higher than cTnI,CK-MB and electrocardiogram(P<0. 01). The mortality rate in patients, with abnormality of serum level of h-FABP,cTnl and CK-MB and ECG, was higher than patients

  10. 慢性肾脏病心肌损害与心型脂肪酸结合蛋白及心肌钙蛋白的相关性分析%Correlation Analysis of Heart Type Fatty Acid Binding Protein and Cardiac Troponin with Myocardial Damage in Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    谢瑜; 沈颖; 罗惠民; 周晓萍; 江勇

    2015-01-01

    分析心型脂肪酸结合蛋白(HFABP)及心肌钙蛋白(cTnI)对慢性肾脏病(CKD)患者缺血性心肌损害的评估应用价值.选取非透析的慢性肾脏病患者,进行腺苷负荷心肌灌注显像检查,同时检测 HFABP、cTnI,并与腺苷负荷试验结果进行对比分析,明确 HFABP 及 cTnI 对缺血性心肌损害的评估价值.结果发现 HFABP 与 eGFR 负相关,与 CREA、BUN 正相关,cTnI 与 IVST、LVPWT 正相关,有31.1%的患者腺苷负荷心肌灌注显像试验阳性,HFABP 在腺苷负荷试验阳性组及阴性组患者间的差异无统计学意义,cTnI 的差异有统计学意义,腺苷负荷试验阳性结果与HFABP 不相关(r =0.041,P =0.654),与 cTnI 正相关(r =0.649,P <0.01).结果表明:HFABP受肾小球滤过率的影响较大,不是反映慢性肾脏病患者缺血性心脏损害的理想指标,cTnI 不受年龄和肾功能的直接影响,是腺苷负荷心肌灌注缺损的独立危险因素,腺苷负荷核素心肌灌注显像是评估 CKD 患者冠状动脉疾病的有效手段.%The ischemic myocardial damage evaluation value of heart type fatty acid binding protein and cardiac troponin I in CKD patients is explored in this paper.Adenosine stress myocardial perfusion imaging is performed to all patients whose levels of HFABP and cTnI are also measured and compared with adenosine stress test results to assess the ischemic myocardial damage evaluation value of HFABP and cTnI.It is observed that HFABP is negatively correlated with eGFR,and positively correlated to CREA and BUN,and that cTnI is positive corre-lated with IVST and LVPWT.31.1% patients have positive results in adenosine stress test,the positive results being positively correlated with cTnI(r =0.649,P <0.01),and having no correlation with HFABP (r =0.041, P =0.654).The results show that HFABP is strongly influenced by glomerular filtration rate,and thus not an i-deal index of

  11. 心型脂肪酸结合蛋白、肌钙蛋白Ⅰ与脑卒中继发性肺栓塞的关系%Association between heart-type fatty acid binding protein, cardiac tro-poninⅠand stroke-associated pulmonary embolism

    Institute of Scientific and Technical Information of China (English)

    韩芳; 张伟东; 廖晓凌; 王拥军

    2014-01-01

    Objective To investigate the diagnosis and prognostic value of heart-type fatty acid binding protein com-bined cardiac troponin Ⅰ in stroke-associated pulmonary embolism patients. Methods 150 patients with stroke-asso-ciated pulmonary embolism (study group) and 150 patients of stroke without pulmonary embolism (control group) from January 2011 to April 2014 in Luhe Hospital of Tongzhou District in Beijing City were selected in this study. The H-FABP and cardiac troponin Ⅰ of patients in two groups before treatment and those of the study group after treatment were detected and compared. Results The levels of plasma H-FABP and cardiac troponin Ⅰ of patients before treat-ment in study group [(9.52±2.67), (0.15±0.09) μg/L ] were higher than those of the control group [(3.87±2.96), (0.05±0.03) μg/L], the differences were statistically significant (P<0.05).After treatment, the levels of plasma H-FABP and cardiac troponinⅠ in study group [(5.51±1.97), (0.08±0.03) μg/L] were decreased than pretreatment, the differences were statistically significant (P<0.05). Conclusion The level of H-FABP and cardiac troponinⅠ increasing obviously in stroke-associated pulmonary embolism, and the detection of the two indexs can be helpful for the disease diagnosis and the access of short-time prognosis.%目的:探讨心型脂肪酸结合蛋白(H-FABP)联合肌钙蛋白Ⅰ(cTnⅠ)对脑卒中继发性肺栓塞患者早期诊断及判断预后的价值。方法选取2011年1月~2014年4月北京市通州区潞河医院收治的150例脑卒中继发性肺栓塞患者(研究组)及单纯脑卒中患者150例(对照组)。检测并比较治疗前两组及研究组治疗前后H-FABP、cTnⅠ水平。结果治疗前研究组H-FABP [(9.52±2.67)μg/L]及cTnⅠ[(0.15±0.09)μg/L]水平明显高于对照组[(3.87±2.96)、(0.05±0.03)μg/L],差异均有统计学意义(P<0.05);治疗后研究组患者血浆H-FABP、cTnⅠ水平分别为(5.51±1.97)、(0.08±0.03)

  12. 脂肪细胞型脂肪酸结合蛋白对冠心病危险程度预测价值的研究%Study on Predictive Value of Adipocyte Fatty Acid-binding Protein for Coronary Heart Disease Risk Degree

    Institute of Scientific and Technical Information of China (English)

    王峰; 刘帮助

    2013-01-01

    目的 探讨脂肪细胞型脂肪酸结合蛋白(A-FABP)表达在冠心病危险程度预测中的价值,为其防治提供依据.方法 回顾性分析经过冠状动脉造影确诊为冠心病观察组76例、同期26例阴性对照组患者的血清A-FABP表达水平、平板运动试验Duke评分,揭示A-FABP表达与冠心病危险程度之间的相关性.结果 A-FABP在冠心病观察组表达水平显著高于对照组(P <0.001),在多支病变、双支病变中A-FABP表达水平高于单支病变(P<0.05);A-FABP表达水平与Duke评分、冠状动脉病变支数、总胆固醇呈正相关,与高密度脂蛋白胆固醇水平呈负相关(P<0.05).结论 A-FABP表达与冠心病的发病及病变程度密切相关,可能对冠心病的危险程度具有一定的预测价值.%Objective To explore the predictive value of adipocyte fatty acid-binding protein (A-FABP)expression for coronary heart disease,providing guidance for the prevention and treatment.Methods A-FABP expression level and Duke score in observation group of 76 patients after coronary angiography diagnosed as coronary heart disease and 26 cases of negative controls were retrospectively analyzed to reveal the correlation between the risk degree of coronary heart disease and A-FABP expression.Results A-FABP expression level in patients with coronary heart disease was significantly higher than in the control group(P <0.001).A-FABP expression level in multi-and double-vessel lesions group were significantly higher than in single-vessel lesion and the control group(P < 0.05).A-FABP expression level was positively correlated with Duke score,coronary artery lesions and total cholesterol,and is negatively correlated with high density lipoprotein cholesterol levels(P < 0.05).Conclusion A-FABP expression is closely related with the onset and severity of coronary artery disease,and may have some predictive value for the risk degree of coronary heart disease.

  13. 血浆脑钠肽及脂肪酸结合蛋白水平与慢性收缩性心力衰竭关系的探讨%Investigation of the relationships among plasma B type natriuretic peptide,fatty acid binding protein and chronic congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    曹磊

    2011-01-01

    目的 测定慢性收缩性心力衰竭(CHF)患者的血浆脑钠肽(BNP)及血清脂肪酸结合蛋白(FABP)水平,探讨血浆BNP及血清FABP对CHF诊断及心功能评估的价值.方法 选择住院CHF患者60例,其中NYHA I级12例,II级18例,III级20例,IV级10例;原发疾病:冠心病30例,瓣膜性心脏病9例,扩张型心肌病10例,高血压性心脏病11例.另纳入20例健康体检者为健康对照组,分别测定BNP及FABP浓度,评价心功能.结果 CHF组血浆BNP及血清FABP水平显著高于健康对照组(PNYHA III级>NYHA II级,P均40%患者(P0.05).BNP与FABP呈正相关(r=0.801,P<0.01),两者与LVEF呈负相关(r=-0.718,r=-0.881,P<0.01).结论 血浆BNP及血清FABP测定对CHF的诊断和心功能的分级及预后判断都有重要的临床价值.%Objective To determine the plasma B type natriuretic peptide ( BNP ) and fatty acid binding protein ( FABP ) levels in patients with chronic heart failure ( CHF ), and to investigate the value of plasma BNP and FABP in diagnose of patients with chronic heart failure and in assessment of cardiac function. Methods There were 60 cases of CHF, according to NYHA classification, 12 cases were in degree of Ⅰ, 18 cases were Ⅱ, 20 were Ⅲ, 10 cases in IV. Primary disease:30 cases with CHD,9 cases with valvular heart disease,10 cases with dilated cardiomyopathy, 11 cases with hypertensive heart disease. The plasma BNP and FABP concentration in these 60 patients with chronic heart failure and 20 controls were determined, cardiac function assessment was conducted. Results Level of plasma BNP and FABP in CHF group were significantly higher than that of the control group( P < 0.01 ); and with the increase of degree of heart failure, plasma BNP and FABP levels gradually increased( NYHA Ⅳ > NYHA Ⅲ > NYHA Ⅱ, P < 0.01 ), meanwhile patients with LVEF ≤40% significantly higher than patients with LVEF > 40% ( P < 0.01 ). BNP was positively correlated with FABP( r = 0. 801, P < 0

  14. 肠脂肪酸结合蛋白在急腹症患者中鉴别急性肠缺血的价值%The value of serum intestinal fatty acid binding protein measurement in discriminating intestinal ischemia in patients with acute abdomen

    Institute of Scientific and Technical Information of China (English)

    石卉; 吴本俨; 刘文徽; 苏斌斌; 李婷婷

    2012-01-01

    目的 评估肠脂肪酸结合蛋白( I-FABP)在急腹症患者中鉴别急性肠缺血的价值.方法 2009年11月至2011年8月解放军总医院151例住院急腹症患者及17例健康对照者纳入本研究,测定其血清I-FABP水平,根据ROC曲线计算I-FABP诊断急性肠缺血的临界值、敏感性、特异性、阳性似然比、阴性似然比、阳性预测值、阴性预测值,评估其诊断及鉴别诊断价值.结果 151例急腹症患者中急性肠缺血24例,非肠缺血127例.肠缺血组的I-FABP水平[(109.67 ±48.82)μg/L]明显高于非肠缺血组[(36.78±11.25) μg/L]和健康对照组[(8.33±6.25) μg/L],P值均<0.01.I-FABP的诊断临界值为87.52 μg/L,I-FABP诊断急性肠缺血的敏感度为0.762,阴性预测值为0.963,阳性似然比3.05,阴性似然比0.24.结论 血清I-FABP用于鉴别急腹症中急性肠缺血患者具有临床诊断价值.%Objective To assess the differential diagnostic value of serum intestinal fatty acid binding protein (I-FABP) in distinguishing intestinal ischemia patients from acute abdomen patients.Methods A total of 151 patients with acute abdomen and 17 healthy controls from the PLA General Hospital were enrolled from November,2009 to August,2011. Serum I-FABP levels were measured by ELISA.According to the ROC curve,the cut-off value,sensitivity,specificity,positive likelihood ratio (PLR),negative likelihood ratio ( NLR),positive predietive value (PPV) and negative predictive value (NPV) were calculated. Results Of the 151 acute abdomen patients,there were 24 intestinal ischemia patients and 127 without intestinal ischemia.Serum I-FABP level in intestinal ischemia group [( 109.67 ±48.82) μg/L]was significantly higher than those in patients without intestinal ischemia [(36.78 ± 11.25) μg/L]and healthy controls[(8.33 ±6.25) μg/L]( all P values <0.01 ).The serum I-FABP cut-off value for the diagnosis of intestinal ischemia was 87.52 μg/L.Serum I-FABP was efficient in terms of

  15. Heart-type fatty acid-binding protein in plasma and urine for the early diagnosis of acute myocardial infarction%血浆和尿液心型脂肪酸结合蛋白与急性心肌梗死的早期诊断

    Institute of Scientific and Technical Information of China (English)

    王宏运; 何海超; 王绍欣; 李转珍; 姚慧霞; 张东江

    2012-01-01

    目的 通过心型脂肪酸结合蛋白(H-FABP)与其他生化标记物的比较,探讨心型脂肪酸结合蛋白(H-FABP)对急性心肌梗死(AMI)患者的早期诊断价值.方法 本研究采用固相夹心酶联免疫法(ELISA)测定64例AMI患者血浆心肌肌钙蛋白(cTnI)、肌酸激酶同工酶(CK-MB)、肌红蛋白(MYO)、H-FABP浓度;同时选取非急性心肌梗死患者53例作为对照组.H-FABP采用两种检测方法:固相夹心酶联免疫法和胶乳比浊法免疫测定(LTIA).结果 cTnT,CK-MB,MYO,H-FABP( by ELISA),H-FABP (by LTIA),心电图(ECG)诊断AMI敏感性分别为39.1%,59.4%,64.1%,68.7%,70.3%和54.7%;特异性为:98.1%,71.7%,81.1%,77.4%,90.6%和92.5%.结论 对AMI患者的诊断,H-FABP(by LTIA)优于cTnT,CK-MB,MYO,H-FABP( by ELISA),ECG.%Objective To investigate the early diagnostic value of heart-type fatty acid-binding protein ( H-FABP) for acute myocardial infarction( AMI),by comparing with other biochemical markers.Methods The concentrations of serum H-FABP,cTnI.CK-MB,MYO of 64 patients with AMI were detected by ELISA.Meanwhile 53 patients without acuter myocardial infarction were also selected as the control group.H-FABP was measured by two immunoassays,the H-FABP enzyme-linked immunosorbent assay( ELISA) and the H-FABP latex turbidimetric immunoassay ( LTIA).Results Sensitivities of cTnI,CK-MB,MYO,H-FABP ( by ELISA).H-FABP ( by LTIA),and electrocardiogram ( ECC) for the diagnosis of AMI were 39.1%,59.4%,64.1%,68.7%,70.3% and 54.7%,respectively.Specificities of cTnT,CK-MB,myoglobin,H-FABP ( by ELISA),H-FABP ( by LTIA),and ECG were 98.1%,71.7%,81.l%,77.4%,90.6% and 92.5%,respectively.Conelusions H-FABP ( by LTIA) is superior to cTnT,CK-MB,MYO,and H-FABP ( by ELISA) tests for the diagnosis of AMI in patients.

  16. Heart-type fatty acid binding protein in the early diagnosis of myocardial infarction after off-pump coronary artery bypass%心肌型脂肪酸结合蛋白早期快速诊断OPCAB术后心肌梗死

    Institute of Scientific and Technical Information of China (English)

    孟冬梅; 李培军; 刘子后; 李杰; 孙静; 郭志刚; 刘建实

    2012-01-01

    目的 探讨心肌型脂肪酸结合蛋白(H-FABP)对非体外循环不停跳冠状动脉旁路移植术(OPCAB)术后心肌梗死的早期快速诊断价值.方法 2009年3月至7月,59例患者行首次单纯OPCAB.根据围手术期肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白Ⅰ(cTnI)值及心电图、超声心动图的变化将患者分为正常组(Ⅰ组)、心肌损伤组(Ⅱ组)和心肌梗死组(Ⅲ组),分析各组H-FABP、CK-MB、cTnI含量的变化,并应用ROC曲线分析H-FABP诊断术后急性心肌梗死的诊断截断点和应用价值.结果 Ⅲ组的H-FABP水平显著高于Ⅱ组及Ⅰ组(P<0.01),H-FABP峰值出现时间早(人ICU 2 h即达到高峰),维持时间短(入ICU 4 h即开始下降),术后1天回到基线水平.经ROC曲线检验,以H-FABP 22μg/L为心肌梗死的诊断截断点,入ICU即刻诊断灵敏度为90.9%,特异性为77.1%.入ICU 2 h的H-FABP值灵敏度为72.7%,特异性为75.0%.结论 H-FABP有助于OPCAB术后心肌梗死的早期快速诊断.%Objective To evaluate the early diagnostic value of Heart-type fatty acid-binding protein(H-FABP) for myocardial infarction in patients post off-pump coronary artery bypass (OPCAB).Methods Between March 2009 and July 2009,59 patients had been undergone OPCAB for the first time.They were divided into 3 groups (normal group,myocardial injury group and myocardial infarction group) by myocardial-bound creatiue kinase (CK-MB) 、cardiac troponio Ⅰ (cTnI) 、electrocardiogram (ECG) and echocardiogram.Serial blood samples were taken during perioperation to quantify blood levels of H-FABP,CK-MB,cTnI.Results The average H-FABP value for the patients in the myocardial infarction group is higher than the others ( P < 0.01 ).H-FABP reached the peak valve at 2 hours and decreased at 4 hours after the patients arrived at ICU.H-FABP got back to the baseline one day postoperation.Receiver operating characteristic curves( ROC curve) demonstrated that H-FABP had greater diagnostic

  17. Value of Urine Liver-Type Fatty Acid Binding Proteins in the Early Diagnosis of Acute Kidney Injury in Critically Ill Patients%肝型脂肪酸结合蛋白在重症患者急性肾损伤早期诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    黄云芳; 陈文莉; 方珣

    2011-01-01

    目的:探讨尿肝型脂肪酸结合蛋白(L-FABP)在重症患者急性肾损伤(AKI)中的早期诊断价值。方法:以我院收治的危重症患者为观察对象,按照阿姆斯特丹AKI诊断标准,将5d内符合诊断标准的AKI患者纳入AKI组(12例),对照组(12例)由匹配的非AKI患者构成。每24 h收集尿标本,持续5d。ELISA法检测尿L-FABP水平。以受试者工作特征曲线评价L-FABP对AKI的诊断作用。结果:与AKI诊断前3d比较,AKI诊断前2d及1d患者尿L-FABP均明显增高(P均<0. 05),但尿N-乙酰-β-D氨基葡萄糖苷酶(NAG)及血肌酐(Scr)无明显改变(P均>0.05);观察期间对照组尿L-FABP、NAG、Scr均无明显变化(P均>0.05)。AKI诊断前3d尿L-FABP、NAG、Scr对AKI均无诊断作用;AKI诊断前2d及1d尿L-FABP对AKI具有早期诊断作用,而NAG、Scr无早期诊断作用。结论:尿L-FABP对重症患者AKI具有较高的敏感性和特异性,可能具有AKI早期诊断价值。%Objective: To investigate the value of urinary liver-type fatty acid binding proteins (L-FABP) in the early diagnosis of acute kidney injury (AKI) in critically ill patients. Methods: Critically ill patients were divided into the AKI group ( n=12) and non-AKI group (n=12). Blood and urinary samples were collected daily for five days. The samples were used to determine serum creatinine(Scr) , N-acetyl-β-D-glucosaminidase (NAG), as well as urinary L-FABP. Standard statistic analysis was used along with receiver operating characteristic curve analysis to evaluate the diagnose value. Results: There were no significant differences in clinical parameters between non-AKI (n=14) and AKI (n = 12) groups. As compared with the levels obtained three days before the diagnosis of AKI, the urinary L-FABP levels in the AKI group increased significantly (P0. 05). The levels of urinary L-FABP, Scr and NAG had no significant changes in the control group (all P> 0.05). Conclusion; Urinary L

  18. 心型脂肪酸结合蛋白在心梗患者行介入治疗中的意义%The study of heart-type fatty acid binding protein in the PCI therapy for patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    张健; 李春盛

    2013-01-01

    目的 观察ST段拾高型心肌梗死患者行经皮冠脉介入治疗(PCI)前后心型脂肪酸结合蛋白(H-FABP)变化及意义.方法 选择北京朝阳医院急诊科确诊ST段抬高型心肌梗死患者178例,根据PCI术后ST段回落程度分为两组,即ST段回落组及ST段无回落组,分别为137人及41人.所有病例均于入院即刻测定H-FABP及心肌肌钙蛋白(cTnI),并在PCI术后1h,6h,12 h和24 h再分别测定H-FABP质量浓度,PCI术后12h及24 h测定cTnI.测定PCI术后2 hST段回落幅度(ΣSTR).结果 ST段回落组及ST段无回落组PCI术前人口统计学资料差异无统计学意义.两组患者术后6 h H-FABP明显高于术前(P<0.05),ST段回落组患者于24 h H-FABP恢复至正常水平,而ST段无回落组患者H-FABP未降至正常水平.结论 ST段抬高型心肌梗死患者血清H-FABP升高与冠脉病变程度有关,PCI术可影响H-FABP变化,ΣSTR≥50%与H-FABP降至正常水平以下有利于判断患者的心肌损伤程度和心肌再灌注.%Objective To observe the change and clinical significance of the heart type fatty acid binding protein (H-FABP) in ST Segment Elevation Myocardial Infarction (STEMI) after percutaneous coronary intervention (PCI).Methods Of 178 STEMI patients were recruited and were separated as ST segment drop group (137) and ST segment non-drop group (41).All the patients received H-FABP and cTnI tests,and re-tested H-FABP on 1 h,6 h,12 h and 24 h after the PCI,and re-tested cTnI on 12 h and 24 h after the PCI.Also,the ST segment drop amplitude (ΣSTR) was measured 2 h after the PCI.Results The demographics of both groups were similar.In both groups,the H-FABP on 6 h after PCI was significantly higher than the value measured prior to PCI.In the ST segment drop group,the H-FABP was reduced to normal value on 24 h after PCI,while it was not in the ST segment non-drop group.Conclusions The H-FABP elevation is associated with the severity of coronary lesions in ST segment elevation

  19. Transcriptional enhancer from milk protein genes

    Energy Technology Data Exchange (ETDEWEB)

    Casperson, Gerald F. (Ballwin, MO); Schmidhauser, Christian T. (Berkeley, CA); Bissell, Mina J. (Berkeley, CA)

    1999-01-01

    The invention relates to novel enhancer nucleotide sequences which stimulate transcription of heterologous DNA in cells in culture. The enhancers are derived from major milk protein genes by the process of deletion mapping and functional analysis. The invention also relates to expression vectors containing the novel enhancers.

  20. Transcriptional enhancer from milk protein genes

    Energy Technology Data Exchange (ETDEWEB)

    Casperson, G.F.; Schmidhauser, C.T.; Bissell, M.J.

    1999-12-21

    The invention relates to novel enhancer nucleotide sequences which stimulate transcription of heterologous DNA in cells in culture. The enhancers are derived from major milk protein genes by the process of deletion mapping and functional analysis. The invention also relates to expression vectors containing the novel enhancers.

  1. Widely predicting specific protein functions based on protein-protein interaction data and gene expression profile

    Institute of Scientific and Technical Information of China (English)

    GAO Lei; LI Xia; GUO Zheng; ZHU MingZhu; LI YanHui; RAO ShaoQi

    2007-01-01

    GESTs (gene expression similarity and taxonomy similarity), a gene functional prediction approach previously proposed by us, is based on gene expression similarity and concept similarity of functional classes defined in Gene Ontology (GO). In this paper, we extend this method to protein-protein interaction data by introducing several methods to filter the neighbors in protein interaction networks for a protein of unknown function(s). Unlike other conventional methods, the proposed approach automatically selects the most appropriate functional classes as specific as possible during the learning process, and calls on genes annotated to nearby classes to support the predictions to some small-sized specific classes in GO. Based on the yeast protein-protein interaction information from MIPS and a dataset of gene expression profiles, we assess the performances of our approach for predicting protein functions to "biology process" by three measures particularly designed for functional classes organized in GO. Results show that our method is powerful for widely predicting gene functions with very specific functional terms. Based on the GO database published in December 2004, we predict some proteins whose functions were unknown at that time, and some of the predictions have been confirmed by the new SGD annotation data published in April, 2006.

  2. Widely predicting specific protein functions based on protein-protein interaction data and gene expression profile

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    GESTs (gene expression similarity and taxonomy similarity), a gene functional prediction approach previously proposed by us, is based on gene expression similarity and concept similarity of functional classes defined in Gene Ontology (GO). In this paper, we extend this method to protein-protein interac-tion data by introducing several methods to filter the neighbors in protein interaction networks for a protein of unknown function(s). Unlike other conventional methods, the proposed approach automati-cally selects the most appropriate functional classes as specific as possible during the learning proc-ess, and calls on genes annotated to nearby classes to support the predictions to some small-sized specific classes in GO. Based on the yeast protein-protein interaction information from MIPS and a dataset of gene expression profiles, we assess the performances of our approach for predicting protein functions to “biology process” by three measures particularly designed for functional classes organ-ized in GO. Results show that our method is powerful for widely predicting gene functions with very specific functional terms. Based on the GO database published in December 2004, we predict some proteins whose functions were unknown at that time, and some of the predictions have been confirmed by the new SGD annotation data published in April, 2006.

  3. 心型脂肪酸结合蛋白在急性心肌梗死早期诊断价值的研究%Clinical value of heart-type fatty acid binding protein in the diagnosis of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    周晓茜; 蔡英; 于萍; 朱琛颖; 刘学波

    2013-01-01

    Objective To investigate the value of heart - type fatty acid binding protein (H -FABP) in the early diagnosis of acute myocardial infarction ( AMI). Methods 68 patients admitted to hospital with acute chest pain were selected in this study, and were divided into unstable angina pectoris (UAP) group and acute myocardial infarction (AMI)group according to the clinical diagnosis including ECG and the results of coronary arteriography. Serum H - FABP concentrations were tested by using ELISA method at 3 h ( H - FABP3) and 6 h ( H - FABP6) after the chest pain. The sensitivity, specificity, positive predictive value, negative predictive value were compared with hsTnT and CK -MB. Results Serum H - FABP3 and H - FABP6 concentrations were significantly higher in group AMI than in group UAP ( P < 0. 05 ). The sensitivity, specificity, positive predictive value, negative predictive value of H - FABP3 in the diagnosis of AMI were 87.0% , 81.8% , 90. 9% , 75.0% , while in H - FABP6 were 95.7% 、90. 9% 、95. 7% 、90.9% . The data of H - FABP6 were significantly higher than those of HABP3 except positive predictive value(P <0. 05) ; Further, the sensitivity and negative predictive value of H - FABP were significantly higher than those of hsTnT and CK - MB (P < 0. 05). Conclusion The serum H - FABP concentrations of patients were significantly increased at the early stage of AMI. The sensitivity and specificity of H - FABP in the early diagnosis of AMI were significantly higher than those of hsTnT and CK - MB.%目的 探讨心型脂肪酸结合蛋白(H-FABP)在急性心肌梗死(AMI)早期的诊断价值.方法 选择急诊胸痛可疑心肌梗死入院患者68例,根据患者的临床症状、心电图及冠状动脉造影结果将患者分为不稳定型心绞痛组(UAP组,共22例)和AMI组(共46例).分别在患者胸痛发生后3h和6h抽取静脉血5 mL,ELISA法定量测定血清H-FABP浓度.分别计算H-FABP在AMI诊断中的敏感度、特异度、阳性预测值及

  4. 吉非罗齐对游离脂肪酸和脂肪型脂肪酸结合蛋白在血脂异常兔中影响%Influence of gemfibrozil on levels of adipocyte fatty acid-binding protein in serum of dyslipidemia rabbits

    Institute of Scientific and Technical Information of China (English)

    谷祥任; 吴洁; 杜克炜

    2011-01-01

    Objective To observe the effects of gemfibrozil on serum free fatty acid(FFA) concentration and adipocyte fatty acid- binding protein(AFABP) secretion by adipose tissue from hypercholesterolemia rabbits. Methods Fifteen male New Zealand white rabbits were randomly divided into three groups. ①Control group was fed with normal diet for 12 weeks;②high cholesterol group was fed with high cholesterol group diet for 12 weeks;③gemfibrozil group was fed with same cholesterol diet for eight weeks supplemented with gemfibrozil 200 mg · kg-1 · d-1 for 4 weeks.Each group had five rabbits. FFA and AFABP concentrations in serum and adipose tissue culture supernatant were measured by enzyme-linked immunosorbent assay(ELISA). Adipose tissue was harvested for reverse transcriptionpolymerase chain reaction(RT-PCR) studies. Results After 8 and 12 weeks,rabbits from high cholesterol group and gemfibrozil group showed higher serum levels of total cholesterol, low density lipoprotein cholesterol and FFA than those of control group( P <0. 01). Gemfibrozil treatment significantly decreased body mass of rabbits in the twelfth week than in the eighth week ( P <0. 05). AFABP concentrations in serum and in culture supernatants of adipose tissue were decreased in gemfibrozil group compared with high-cholesterol group at the end of the twelfth week ( P < 0.05). The mRNA levels of AFABP in adipose tissue were increased in high cholesterol group and gemfibrozil group compared with control group ( P < 0. 05); but the mRNA levels of AFABP in adipose tissue was decreased in gemfibrozil group compared with high-cholesterol group( P <0.05). Conclusion The study indicated that gemfibrozil reduced body mass and reduced FFA and AFABP serum concentration and adipose tissue secretion ot hypereholesterolemia rabbits. These effects might be of significance for the treatment of atherosclerosis and of obesity prevention.%目的 现察吉非罗齐短期干预对高胆固醇血症兔血清游

  5. 肠脂肪酸结合蛋白在肺炎合并胃肠功能损伤患儿血清中的变化及意义%Change in serum intestinal fatty acid binding protein and its significance in children with pneumonia and gastrointestinal injury

    Institute of Scientific and Technical Information of China (English)

    范晓蕾; 李海英; 陈晓昕; 谢垒; 王怀立

    2016-01-01

    目的:探讨肠脂肪酸结合蛋白(IFABP)在社区获得性肺炎患儿血清中的变化及与胃肠功能损伤的相关性。方法选择2015年1月至10月的社区获得性肺炎患儿82例(轻症34例,重症48例),根据小儿危重病例评分(PCIS)将重症肺炎患儿分为非危重组(25例)和危重组(23例);另选取体检的健康儿童30例作为对照组。采用酶联免疫吸附法检测血清 IFABP 浓度,并对重症肺炎患儿进行急性胃肠损伤(AGI)分级。比较各组间血清 IFABP 浓度的差异,并对 IFABP 与 AGI 分级和 PCIS 进行相关性分析。结果重症肺炎血清 IFABP 浓度均高于对照组和轻症肺炎组(均 P<0.01),轻度肺炎组血清 IFABP 浓度亦明显高于对照组(P<0.01)。危重组血清 IFABP 浓度高于非危重组(P<0.01)。AGI 1~4级组血清 IFABP 均高于对照组(P<0.01),而且随着 AGI 级别的增高,血清 IFABP 浓度也逐渐增高,差异有统计学意义(P<0.01)。IFABP 与 AGI 分级呈正相关(P<0.01);与 PCIS 呈负相关(P<0.01)。结论肺炎患儿血清 IFABP 均有所增高,血清 IFABP 可以作为肺炎患儿合并胃肠损伤早期诊断和病情评估的敏感指标。%Objective To study the change in serum intestinal fatty acid binding protein (IFABP) in children with pneumonia and its correlation with gastrointestinal injury. Methods A total of 82 children with community-acquired pneumonia who were treated from January to October, 2015 were enrolled, among whom 34 had mild pneumonia and 48 had severe pneumonia. According to pediatric critical illness score (PCIS), the children with severe pneumonia were further divided into non-critical group (25 patients) and critical group (23 patients). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. ELISA was used to measure serum IFABP level, and the acute gastrointestinal injury (AGI

  6. Value of urinary liver-type fatty acid binding protein in prediction of renal function progression in patients with chronic glomerulonephritis%尿肝型脂肪酸结合蛋白预测慢性肾小球肾炎进展的价值

    Institute of Scientific and Technical Information of China (English)

    徐维佳; 李佳琳; 王琴; 施蓓莉; 牟姗; 倪兆慧

    2012-01-01

    Objective To evaluate the value of urinary liver-type fatty acid binding protein (L-FABP)as a biomarker in prediction of renal function progression in patients with chronic glomerulonephritis (CGN). Methods A total of 123 patients with newly diagnosed CGN by renal biopsy in Shanghai Renji Hospital between 2004 January and 2005 December were enrolled in the study,Twenty-eight healthy subjects were used as control group.Urine samples were collected before biopsy and treatment,and urinary L-FABP was measured by ELISA.The patients with follow-up every three months for 5 years were divided into progressive group and nonprogressive group.The progression of kidney function impairment was defined as a reduction of GFR ≥ 5 ml·min-1·(1.73 m2)-1·year-1 during follow-up.The risk factors of progressive renal function were evaluated and the Spearman correlation analysis was performed to find out the prognostic indicator of renal function deterioration. Results Urinary L-FABP level of CGN patients was significantly higher than that of healthy control group (P<0.01).Urinary L-FABP in CGN patients was negatively correlated with eGFR (r=-0.565,P<0.01) and positively correhted with proteinuria (r=0.501,P<0.01) and Scr (r=0.601,P<0.01).Kaplan-Meier analysis showed that urinary L-FABP excretion>76.58 μg/g·cr predicted progression of renal function.The AUC of urinary L-FABP for prognosis of CGN progression was 0.95,with 87.5% of sensitivity and 90.5%of specificity at the cutoff value of 119.8 μg/g·cr,which revealed its great value of predicting the prognosis of CGN patients. Conclusion Urinary L-FABP can be a novel biomarker of evaluation for renal injury and early progressive renal function deterioration in patients with CGN.%目的 评估尿肝型脂肪酸结合蛋白(L-FABP)预测慢性肾小球肾炎(CGN)病情进展的临床价值.方法 前瞻性入选2004年1月至2005年12月期间在我院行肾穿刺活检明确病理诊断的原发性CGN患者123

  7. Value of serum liver fatty acid-binding protein in monitoring of hepatic function after the ischemia-reperfusion injury%血清肝型脂肪酸结合蛋白在大鼠肝脏缺血再灌注损伤的早期诊断价值

    Institute of Scientific and Technical Information of China (English)

    门贺伟; 杨龙; 张荣信; 薛振毅; 蔡金贞; 张雅敏

    2012-01-01

    Objective To investigate the diagnostic value and significance of serum liver fatty acid-binding protein (L-FABP) in hepatic ischemia-reperfusion injury in rat.Methods Male Wistar rats were randomly divided into three groups:sham operation group (group A) ; reperfusion after 15 min of ischemia group (group B) ; reperfusion after 30 min of ischemia group (group C).Each group was divided into 6 subgroups based on the time of reperfusion (15 min,1 h,3 h,6 h,1 d,3 d).The model of hepatic ischemia-reperfusion injury was established,the level of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and L-FABP were tested at each time point and the expression of L-FABP was tested by Immunohistochemical Fluorescence.The pathological changes observed in the liver and evaluated the changes by Suzuki's scoring system.Results Compared with group A,the changes of serum L-FABP:increased after 15 min of reperfusion [(0.57 ± 0.14) μg/L,P < 0.05],reached the peak after 3 h of reperfusion [(1.70 ± 0.26) μg/L,P < 0.05] and returned to normal at 3 d [(0.16 ± 0.05) μg/L,P >0.05] ; the changes of serum ALT and AST:no significant increase after 15min of reperfusion,reach the top at 6h and the level was still higher than normal at 3 d (P < 0.05) ; L-FABP in liver tissue:the expression was decreased after 15min of reperfusion (0.148 ± 0.047,P < 0.05),reached to the trough at 3 h (0.071 ± 0.019,P < 0.05) and returned to normal at 3 d (0.142 ± 0.047,P > 0.05).Compared with group B,the level of serum L-FABP,AST and ALT in group C were significandy increased at each time point (P < 0.05),and the expression of L-FABP was significantly decreased (P < 0.05),the pathological changes were significantly worse.Conclusion Compared with the traditional indicator of liver function (ALT,AST),L-FABP is the more sensitive indicator to monitor the hepatic ischemia-reperfusion injury,and it consistents with the changes in the liver tissue pathology.%目的 探讨血清

  8. 肝型脂肪酸结合蛋白与非酒精性脂肪性肝病严重程度及其他指标关系探讨%Correlation between liver-type fatty acid binding protein and nonalcoholic fatty liver disease extent and other clinical parameters

    Institute of Scientific and Technical Information of China (English)

    李冰; 沈芊; 黄辉红; 郭娟荪; 汪道伟

    2013-01-01

    目的 探讨血清肝型脂肪酸结合蛋白(L-FABP)与非酒精性脂肪性肝病(NAFLD)患者疾病严重程度及脂代谢相关临床生化指标的相互关系.方法 选择96例NAFLD患者(观察组)及100例健康体检者(对照组),用酶联免疫吸附法测定血清L-FABP及血生化指标,超声判定病变程度,同时计算体质指数(BMI)、腰臀比(WHR)及稳态模型评估法胰岛素抵抗指数(HOMA-IR).结果 观察组WHR、BMI、空腹血糖(FBG)、三酰甘油(TG)、丙氨酸氨基转移酶(ALT)、HOMA-IR及L-FABP水平明显高于对照组,差异均有统计学意义(P<0.05).相关性分析结果表明,L-FABP水平与ALT(r=0.735)、TG(r=0.728)、FBG(r=0.681)、WHR(r=0.713)、BMI(r=0.699)、HOMA-IR(r=0.673)均呈正相关(P<0.05),与HDL-C呈负相关(r=-0.607,P< 0.05).对照组L-FABP水平为(15.42±2.51) g/L,轻度NAFLD为(15.96±2.92) g/L,中度NAFLD为(17.48±3.91) g/L,重度NAFLD为(25.14±5.37) g/L.重度NAFLD患者L-FABP水平与对照组及轻、中度NAFLD患者比较差异均有统计学意义(P<0.05).结论 重度NAFLD患者血清L-FABP水平明显增高,L-FABP水平与一些肝功能生化指标有关.%Objective To investigate the correlation between liver-type fatty acid binding protein (L-FABP) and nonalcoholic fatty liver disease (NAFLD) extent and other clinical parameters.Methods Ninety-six patients of NAFLD (NAFLD group) and 100 cases of healthy controls (control group) were selected.The levels of serum L-FABP and blood biochemical parameters were measured by enzyme-linked immunosorbent assay.The lesion degree was assessed by ultrasound.The body mass index (BMI),waist to hip ratio (WHR) and homeostasis model assessment insulin resistance index (HOMA-IR) were calculated.Results The WHR,BMI,fasting plasma glucose (FBG),triglycerides (TG),alanine aminotransferase (ALT),HOMA-IR and L-FABP in NAFLD group were higher than those in control group,there were statistical differences (P < 0.05).The result of correlation

  9. The change of serum fatty acid binding protein and its clinical significance in patients with hepatitis C%血清脂肪酸结合蛋白在丙肝患者中的表达变化及临床意义研究

    Institute of Scientific and Technical Information of China (English)

    毛长庚; 聂亚英; 刘建湘; 肖创清

    2015-01-01

    目的 研究丙肝患者血液中肝型脂肪酸结合酶( L-FABPs)与肝炎活动程度的关系,探讨L-FABPs对丙肝患者肝炎程度的提示和诊断价值. 方法 选取2010年5月至2014年5月于本院就诊并被确诊为慢性丙型肝炎的患者48例(丙肝组)和30名健康人(对照组) ,进行实验室和肝脏活组织检查. 分析并评价相关指标对丙肝患者肝炎程度的诊断价值.结果 丙肝患者的ALT、AST、CRP、MPV和L-FABPs水平均高于健康对照组(P<0. 01);轻度肝炎组患者血清中ALT、AST、L-FABPs明显低于中重度肝炎患者(P<0. 05). 相关分析显示,L-FABPs水平与ALT、AST呈正相关(r=0. 430,P=0. 012;r=0. 337,P=0. 028). 绘制受试者工作曲线,L-FABPs对轻度肝炎患者的诊断曲线下面积为0. 827(95%CI为0. 727~0. 926,P<0. 01),高于AST和ALT对轻度肝炎的诊断曲线下面积(0. 760,0. 775). 当L-FABPs的诊断阈值为12. 6 g/L时,诊断的灵敏度为77%,特异性为87%,假阳性率为13%,假阴性率为23%. 结论 血清L-FABPs的水平随着丙肝肝炎程度的增加而升高,对轻度肝炎的诊断的灵敏度和特异性优于ALT和AST,是追踪随访丙肝患者肝损伤的良好指标,值得临床推广使用.%Objective To detect the change of serum fatty acid binding protein( L-FABPs) in patients with hepatitis C,and to investi-gate the diagnostic value of L-FABPs. Methods 48 hepatitis C patients and 30 healthy controls were selected in this study. Serum bi-ochemical test,and serum L-FABPs were assessed. Results The serum levels of ALT,AST,CRP,MPV and L-FABPs in hepatitis C patients were significantly higher than those of healthy controls(P<0. 01). ALT,AST and L-FABPs in moderate and severe chronic hepatitis patients were significantly higher than those of mild patients(P<0. 05). The serum levels of L-FABPs was positive correlated with ALT(r=0. 430,P=0. 012) and AST (r=0. 337,P=0. 028). Receiver operating characteristic (ROC) curves were used to e-valuate the diagnosis

  10. 心脏型脂肪酸结合蛋白在早期诊断老年人急性心肌梗死中的应用价值%The value of heart-type fatty acid binding protein in the early diagnosis of acute myocardial infarction in elderly patients

    Institute of Scientific and Technical Information of China (English)

    唐江; 方臻飞; 何毅; 郭书红

    2013-01-01

    Objective To investigate the diagnostic value of heart-type fatty acid binding protein (H-FABP) versus cardiac trofonin I (cTnI) and creatinekinase-MB (CK-MB) in early diagnosis of acute myocardial infarction (AMI) in elderly patients.Methods 67 patients with acute chest pain were selceted sequentially and divided into AMI group (n=30) and non-AMI group (n=37).Plasma H-FABP level was rapidly detected by using colloidal gold reagent plate and solid phase immunochromatographic assay for qualitative determination within and after 6 hours of AMI onset.Plasma levels of cTnI and CK-MB were determined within and after 6 hours of onset.The diagnositic value of H-FABP,cTnI and CK-MB in AMI was compared within and after 6 hours of onset.Results The sensitivity of H-FABP was better than that of cTnI and CK-MB within 6 hours of onset (93.3% vs.46.6%,23.3%,both P<0.05).The negative predictive value of H-FABP was better than that of cTnI and CK-MB within 6 hours of onset (94.7% vs.69.8%,61.1%,both P< 0.05) While,positive predictive value and specificity were basically the same between H-FABP,versus cTnI and CK-MB.H-FABP and cTnI levels had significant differences between AMI and non AMI group after 6 hours of onset (all P<0.05).Plasma levels of cTnl and CK-MB were higher after 6 hours than within6 hours [cTnI (4.10±1.79) mg/L vs.(1.45±1.31) mg/L,CK MB(180.52± 158.70) U/L vs.(20.02± 7.97) U/L,both P<0.05].Conclusions As compared with cTnI and CK-MB,within 6 hours after AMI onset,H-FABP as a new myocardial necrosis marker has higher sensitivity,specificity,positive and negative predictive values in the diagnosis of AMI.While,after 6 hours of AMI onset,H-FABP has the same diagnostic value as cTnI and CK-MB.%目的 探讨心脏型脂肪酸结合蛋白(H-FABP)、肌钙蛋白(cTnI)、肌酸激酶同工酶(CKMB)在老年人的急性心肌梗死(AMI)中早期诊断价值. 方法 序贯选择2012年9月至2013年1月67例急性胸痛

  11. 血清脂肪细胞型脂肪酸结合蛋白及脂联素水平与冠心病的相关性%Association between adipocyte fatty acid binding proteins/adiponectin and coronary artery stenosis

    Institute of Scientific and Technical Information of China (English)

    金静; 彭道泉; 龚浩; 赵水平; 宁小晖; 李松林; 王淑慧

    2010-01-01

    Objective To observe the relationship between serum and monocyte-derivedmacrophages secreted adipocyte fatty acid binding protein(A-FABP), adiponectin(or A-FABP/adiponectin ratio)and coronary artery disease. Methods Three hundred and forty subjects underwent coronary angiography(CAG)were classified into CAD group(n = 211)and non-CAD group(n = 129)according to the CAG results. The severity of coronary artery stenosis was assessed by the numbers of involved coronary artery branches and the sum of the Gensini scores. Fasting venous blood was collected from all subjects and peripheral monocytes were isolated from 20 subjects(10 selected from each group with age-, gender-, and BMI-matched). Peripheral blood monocytes were obtained and stimulated into macrophages with PMA, cell culture supernatant was collected. The concentration of serum/supernatant A-FABP and adiponectin levels were assayed by enzyme-linked immunosorbent assays. Results(1)A-FABP levels tendend to be higher in CAD patients compared to non-CAD subjects[18. 3(13.2,22. 8)μg/L vs. 16. 4(13.5,20. 4)μg/L,P = 0. 088]. The concentration of adiponectin in CAD group was significantly lower than those in non-CAD group[13.9(9.8,17.1)mg/L vs. 19.7(14.5,27.6)mg/L,P <0.05].(2)The A-FABP levels increased and the adiponectin levels decreased as the number of stenotic vessels increased. Gensini scores were positively correlated with serum A-FABP(r = 0. 120, P = 0.043)and inversely correlated with adiponectin(r = - 0. 405, P = 0. 007).(3)The difference in A-FABP/adiponectin ratio was moreprominent between subjects with CAD and subjects without CAD[(1.51 ±0. 79)μg/mg vs.(0. 89 ±0. 30)μg/mg, P < 0. 01]and there was a stronger positive correlation of Gensini score to A-FABP/adiponectin ratio(r =0. 531, P =0. 000).(4)Monocyte-derived-macrophages from patients with CAD had higher A-FABP/adiponectin ratio than that in patients without CAD[(0. 51 ± 0. 19)μg/mg vs.(0. 36 ± 0. 11)μg/mg, P < 0. 05]. Conclusions

  12. Prognostic values of heart-type fatty acid-binding protein and D-dimer level in plasma in acute pulmonary embolism patients%心肌型脂肪酸结合蛋白联合血浆D-二聚体对肺栓塞预后评估的临床意义

    Institute of Scientific and Technical Information of China (English)

    陶琳; 杨毅

    2015-01-01

    ObjectiveTo evaluate the clinical value of heart-type fatty acid-binding protein (H-FABP) and D-dimer in assessing the prognosis of acute pulmonary embolism (APE). MethodsTotaly 120 APE patients were hospitalized from January 2011 to December 2014 and enroled in this study. The plasma H-FABP and D-dimer level were measured by enzyme-linked immunosorbent assay. The APE patients were divided three groups including low-risk, middle-risk and high-risk group by European heart association new guidelines. According to the clinical prognosis, the APE patients were divided into survival and death group. The H-FABP and D-dimer level in different groups and the relationship with the prognosis were assessed.ResultsWith the increased severity in patients, the H-FABP and D-dimer level were significantly elevated (P<0.05); the H-FABP and D-dimer level were significantly higher in death group as compared with survival group (P<0.05). The H-FABP and D-dimer level were positively correlated (r=0.693,P=0.000). ROC curves analysis results showed that the area under curve of H-FABP was 0.845 (95%CI: 0.752-0.918), and optimal operating point (OOP) was 8.65 µg/L, which had 81.24% sensitivity and 84.14% specificity; ACU of D-dimer was 0.832 (95%CI: 0.728-0.899), and OOP was 1.25 mg/L, which had 83.72% sensitivity and 82.65% specificity.Conclusion The H-FABP and D-dimer can effectively assess severity and prognosis of APE patients, meanwhile, it provide an objective basis for the clinical individual treatment and reducing the mortality rate of APE patients.%目的:探讨心肌型脂肪酸结合蛋白(H-FABP )联合血浆 D-二聚体在评价急性肺栓塞(APE)患者预后中的临床价值。方法选取本院2011年1月至2014年12月确诊的APE患者120例为研究对象,采用酶联免疫吸附法分别测定外周血H-FABP及D-二聚体浓度。根据病情严重程度将APE患者分为低危组、中危组及高危组;根据临床转归,分为存活组和死亡组

  13. Heart-type fatty acid binding protein for the assessment of the short-term prognosis in acute pulmonary embolism patients with hemodynamic stability on admission%心脏型脂肪酸结合蛋白对人院时血流动力学稳定的急性肺栓塞患者短期预后的评估

    Institute of Scientific and Technical Information of China (English)

    陈勇; 刘双; 郭伟; 王增智

    2013-01-01

    目的 探讨心脏型脂肪酸结合蛋白(H-FABP)对入院时血流动力学稳定的急性肺栓塞患者短期预后评估的临床意义.方法 筛选2009年12月至2010年12月在北京安贞医院就诊并被确诊的入院时血流动力学稳定的急性肺栓塞患者156例,其中符合纳入标准90例,男37例,女53例,平均年龄(61.1±14.6)岁,留取溶栓或抗凝前的外周静脉血标本,应用双抗体夹心酶联免疫吸附法测定H-FABP浓度,非均相免疫法测定肌钙蛋白Ⅰ(cTnI)、N-末端脑钠肽前体(NT-proBNP)浓度,所有患者随访30 d,根据随访结果分为复杂临床过程组(7例)和简单临床过程组(83例),结果采用Mann-Whitney U检验、x2检验、x2检验的连续性校正及logistic回归进行分析.结果 复杂临床过程组H-FABP水平高于简单临床过程组(U =54.000,P<0.01);ROC曲线获得H-FABP的最佳预后截值为7 μg/L,H-FABP、cTnI和NT-proBNP三者之间AUC比较差异无统计学意义;单变量logistic回归分析发现H-FABP≥6 μg,/L、心率≥106次/min和晕厥(均P<0.01)可预测血流动力学稳定的急性肺栓塞患者短期不良预后;多变量logistic回归分析发现仅H-FABP≥6 μg/L和晕厥(均P<0.05)仍是独立预测因素;cTnI或NT-proBNP联合H-FABP可提高对血流动力学稳定的急性肺栓塞患者治疗30 d的预测价值.结论 单独应用H-FABP或H-FABP联合其他临床资料,可对入院时血流动力学稳定的急性肺栓塞患者治疗30 d的预后进行评估,H-FABP作为预后评估可能优于cTnI和NT-proBNP.%Objective To explore the clinical value of heart-type fatty acid binding protein (H-FABP)for the assessment of the short-term prognosis in acute pulmonary embolism (APE)patients with hemodynamic stability on admission.Method A total of 156 APE patients with hemodynamic stability on admission were hospitalized in Beijing Anzhen hospital from December 2009 to December 2010,and the final study population comprised 90

  14. 脂肪细胞型脂肪酸结合蛋白疫苗对高脂喂养雌鼠体重和糖耐量的影响%Effect of Vaccination Against Adipocyte Fatty Acid Binding Protein on Body Weight and Glucose Tolerance in Female Mice with High-Fat Diet

    Institute of Scientific and Technical Information of China (English)

    金昕晔; 邹大进

    2012-01-01

    目的:构建能诱导出针对脂肪细胞型脂肪酸结合蛋白(FABP4)特异性中和抗体的疫苗,为高脂诱导下肥胖和胰岛素抵抗的防治新途径提供理论和实验依据.方法:野生型C57BL/6J雌鼠随机分为疫苗组(n=10,高脂饲养)、佐剂组(n=10,高脂饲养)和空白对照组(n=10,普通饲养),分别予以皮下注射生物合成的FABP4蛋白、佐剂和磷酸盐缓冲液,观察比较各组抗体滴度、安全耐受性和体重、摄食量、空腹血糖、胰岛素抵抗指数(HOMA-IR)、糖耐量实验血糖曲线下面积(AUC)等指标.结果:疫苗组小鼠产生了高滴度的FABP4特异性抗体,并于第3轮加强免疫后达到平衡状态.首次免疫16周后,疫苗组小鼠体重高于空白对照组,但明显低于佐剂组(P<0.05);日平均摄食量高于空白对照组(P<0.05),与佐剂组无差异(P>0.05);空腹血糖、HOMA-IR、腹腔葡萄糖耐量实验AUC均明显低于佐剂组(P<0.05),与对照组无统计学差异(P>0.05).结论:以FABP4作为抗原免疫小鼠,可产生高滴度特异性抗体IgG,有效降低高脂喂养野生型雌性小鼠体重、空腹血糖、HOMA-IR和血糖AUC等指标,为高脂诱导的肥胖和胰岛素抵抗的治疗提供了新的途径和初步证据,可进行深入研究.%Objective: To construct vaccine against adipocyte fatty acid binding protein(FABP4) in order to give theoretical and experimental evidence on prevention and cure of high-fat-induced obesity and insulin resistance. Methods: 30 wild-type female C57BL/6J mice were randomly divided into vaccine group(VG, n=10, with high-fat diet), adjuvant group(AG, n=10, with high-fat diet) and control group(CG, n=10, with normal diet), and were sub-cutaneously injected with biosynthetic FABP4, adjuvant, and phosphate buffered solution, respectively. Several indexes were observed, including antibody titers, security and tolerance, body weight, food intake, fasting blood glucose, homeostasis model of assessment

  15. 对称性肢端角化病皮损中脂肪酸结合蛋白5及二氢硫辛酰胺脱氢酶表达%Expressions of fatty acid binding-protein 5 and dihydrolipoamide dehydrogenase in skin lesions of symmetrical acrokeratoderma

    Institute of Scientific and Technical Information of China (English)

    杨珮珮; 彭晶; 于作忠; 施歌; 黎兆军; 张国学; 樊翌明

    2015-01-01

    Objective To investigate the expressions of fatty acid-binding protein 5 (FABP5)and dihydroli-poamide dehydrogenase(DLD)in skin lesions of symmetrical acrokeratoderma(SAK), and to explore their significance. Methods Biopsy specimens were obtained from skin lesions on the wrists and perilesional skin of 9 patients with SAK, and from normal skin in the wrists of 9 healthy volunteers (control group). Reverse transcription PCR (RT-PCR)and immunohistochemical staining were performed to measure the expressions of FABP5 and DLD in these specimens. Results RT-PCR showed no significant differences in the mRNA expressions of FABP5 or DLD between lesional, perilesional and normal control skin specimens(both P > 0.05). Immunohistochemically, there was a significant increase in the extent and intensity of staining for FABP5 in SAK lesions. Concretely speaking, FABP5 was strongly expressed in the stratum corneum, granular and spinous layers in SAK lesions, but weakly expressed in the stratum corneum, granular and spinous layers in perilesional skin, and only in spinous and basal layers in normal control skin. The expression of DLD decreased in SAK lesions, and was observed only in the stratum corneum and spinous layer in a few cases of SAK. However, the full-thickness epidermis stained positive for DLD in perilesional skin, with the nuclei and cytoplasm both stained deep brown. Conclusion The overexpression of FABP5 in SAK lesions may participate in dysdifferentiation of keratinocytes, while the down-regulation of DLD expression suggests an imbalance in energy metabolism.%目的:探讨脂肪酸结合蛋白5(FABP5)及二氢硫辛酰胺脱氢酶(DLD)在对称性肢端角化病中的表达和意义。方法收集9例对称性肢端角化病患者腕部皮损及其周围皮肤活检标本,9例健康人腕部皮肤为对照,用逆转录 PCR(RT-PCR)及免疫组化法检测 FABP5及 DLD 表达水平。结果 RT-PCR 显示,FABP5 mRNA 及 DLD mRNA 表达在对称性

  16. RBscore&NBench: a high-level web server for nucleic acid binding residues prediction with a large-scale benchmarking database.

    Science.gov (United States)

    Miao, Zhichao; Westhof, Eric

    2016-07-08

    RBscore&NBench combines a web server, RBscore and a database, NBench. RBscore predicts RNA-/DNA-binding residues in proteins and visualizes the prediction scores and features on protein structures. The scoring scheme of RBscore directly links feature values to nucleic acid binding probabilities and illustrates the nucleic acid binding energy funnel on the protein surface. To avoid dataset, binding site definition and assessment metric biases, we compared RBscore with 18 web servers and 3 stand-alone programs on 41 datasets, which demonstrated the high and stable accuracy of RBscore. A comprehensive comparison led us to develop a benchmark database named NBench. The web server is available on: http://ahsoka.u-strasbg.fr/rbscorenbench/.

  17. Engineering genes for predictable protein expression.

    Science.gov (United States)

    Gustafsson, Claes; Minshull, Jeremy; Govindarajan, Sridhar; Ness, Jon; Villalobos, Alan; Welch, Mark

    2012-05-01

    The DNA sequence used to encode a polypeptide can have dramatic effects on its expression. Lack of readily available tools has until recently inhibited meaningful experimental investigation of this phenomenon. Advances in synthetic biology and the application of modern engineering approaches now provide the tools for systematic analysis of the sequence variables affecting heterologous expression of recombinant proteins. We here discuss how these new tools are being applied and how they circumvent the constraints of previous approaches, highlighting some of the surprising and promising results emerging from the developing field of gene engineering.

  18. Comparative analysis of the sialic acid binding activity of four different IBV strains

    OpenAIRE

    2009-01-01

    Abstract Avian infectious bronchitis virus (IBV) is a major pathogen in commercial poultry flocks. Recently we demonstrated, that sialic acid serves as a receptor determinant for IBV on the tracheal epithelium. Here we compared the IBV strains Beaudette, 4/91, Italy02, and QX for their sialic acid binding properties. We demonstrate that sialic acid binding is important for the infection of primary chicken kidney cells and the tracheal epithelium by all four strains. There were only...

  19. The clinical significance of heart type fatty acid-binding protein in diagnosis of acute myocardial infarction%心型脂肪酸结合蛋白在诊断急性心肌梗死中的临床意义

    Institute of Scientific and Technical Information of China (English)

    丁柳美; 唐钧; 倪培华

    2011-01-01

    Objective To study the diagnostic significance of heart type fatty acid-binding protein (H-FABP) in acute myocardial infarction(AMI).Methods H-FABP,cardiac troponin I(cTnI) and creatine kinase (CK)-MB mase were detected in 78 patients with AMI, 52 patients with unstable angina(UA) ,65 patients with stable angina(SA) and 70 healthy controls by double antibody sandwich enzyme-linked immunosorbent assay.32 blood samples were collected within 2 h after AMI occurrence, and 46 blood samples were collected after AMI occurrence more than 2 h.Their H-FABP levels were detected and compared with cTnI.The diagnostic significance was analyzed.Results The levels of H-FABP, CKMB mass and cTnI of AMI group [( 78.12 ± 23.78 ) μg/L, ( 9.48 ± 2.68 ) μg/L and ( 10.12 ± 3.45 ) ng/mL]were significantly higher than those of UA group [( 18.67 ± 7.45 ) μg/L, (0.56 ± 0.11 ) μg/L and (0.21 ± 0.12) ng/mL], SA group [(2.98 ± 1.65) μg/L,(0.22 ±0.08) μg/L and (0.08 ±0.06)ng/mL]and control group [(2.32 ± 1.12) μg/L,(0.20 ±0.09)μg/L and < 0.022 ng/mL](P < 0.05).H-FABP,CK-MB mass and cTnI of UA group were significantly higher than those of SA group and control group ( P < 0.05 ).The H-FABP, CK-MB mass and cTnI levels had no difference between SA group and control group ( P > 0.05 ).The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of H-FABP in AMI diagnosis were 84.89% ,98.8% ,85.89% ,93.24% and 75.14% ,which were higher than CK-MB mass (50.11% ,89.12% ,78.54% ,80.12% and 50.78% ) and cTnI(60.22% ,93.23% ,80.34%,86.45% and 60.56% ) respectively.In the 32 cases' blood collected within 2 h, the positive rate of H-FABP (65.63%)was higher than that of cTnl ( 18.75% ) ( P < 0.05 ).In the 46 cases' blood collected after more than 2h, the positive rate of H-FABP (97.83%) had no statistical difference with that of cTnI (89.13% ) (P > 0.05).Conclusions H-FABP has good sensitivity and

  20. Effect of rt-PA intravenous thrombolytic therapy on serum levels of neuro-specific endolase, C-reactive protein and fatty acid binding protein in patients with early cerebral infarction%rt-PA静脉溶栓对脑梗死早期患者血清神经特异性烯醇酶、C反应蛋白及脂肪酸结合蛋白水平影响研究

    Institute of Scientific and Technical Information of China (English)

    彭道勇; 王晓东; 王茂湘; 范铁平; 邓勇; 王苏平

    2015-01-01

    目的:探讨rt-PA静脉溶栓对脑梗死早期患者血清神经特异性烯醇酶( NSE)、C反应蛋白( CRP)及脂肪酸结合蛋白水平( FABP)的影响。方法收集大连市中心医院收治的急性脑海梗死患者54例,随机分为对照组和实验组,每组27例,2组均给予降低颅内压、改善循环、营养脑细胞常规治疗,对照组在此基础上给予低分子肝素钙注射液5000 U皮下注射,1次/12 h,连续7 d ;实验组在对照组基础上,给予注射用阿替普酶( rt-PA)溶栓治疗,连续7 d,治疗结束后,对所有患者的NSE、CRP及FABP水平进行检测。结果与对照组治疗后比较,实验组患者血清CRP、NSE和FABP水平显著降低(P<0.05)。结论 rt-PA静脉溶栓能够显著降低脑梗死早期患者血清NSE、CRP及FABP水平,改善患者预后,对临床有指导意义。%Objective To analyse effect of rt-PA intravenous thrombolytic therapy on serum levels of neuro-specific endolase, C-reactive protein and fatty acid binding protein in patients with early cerebral infarction.Methods 54 patients who were diagnosed with early acute cerebral infarction in Dalian Municipal Central Hospital were collected.All patients were randomly divided into experimental group and control group,27 cases in each group.Two groups were given conventional treatment,such as reduction of intracranial pressure,improve circulation and nutrition brain cells.Control group was given low molecular weight heparin calcium injection 5000U, one times per 12 h for 7 consecutive days, and experimental group was given rt-PA intravenous thrombolytic therapy on the basis of the control group for 7 consecutive days, post-treatment,the serum levels of NSE, CRP and FABP were detected in all patients.Results Compared with control group post-treatment, the serum CRP,NSE and FABP level was lower in experimental group ( P<0.05).Conclusions The rt-PA intravenous thrombolytic therapy can

  1. Current approach to male infertility treatment: sperm selection procedure based on hyaluronic acid binding ability

    Directory of Open Access Journals (Sweden)

    A. V. Zobova

    2015-01-01

    Full Text Available Intracytoplasmic sperm injection into an oocyte is widely used throughout the world in assisted reproductive technologies programs in the presence of male infertility factor. However, this approach can allow selection of a single sperm, which is carrying different types of pathologies. Minimizing of any potential risks, entailing the occurrence of abnormalities in the embryos development (apoptosis, fragmentation of embryos, alterations in gene expression, aneuploidies is a very important condition for reducing the potential negative consequences resulting the manipulation with gametes. Processes that could be influenced by the embryologist must be fulfilled in safe and physiological way as much as it is possible. Data of numerous publications reporting about the positive effects of using the technology of sperm selection by hyaluronic acid binding, let make a conclusion about the high prospects of this approach in the treatment of male infertility by methods of in vitro fertilization. The selection of sperm with improved characteristics, which determine the maturity and genetic integrity, provides an opportunity to improve the parameters of pre-implantation embryogenesis, having thus a positive effect on clinical outcomes of assisted reproductive technologies programs.

  2. An intron in a ribosomal protein gene from Tetrahymena

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Andreasen, Per Hove; Dreisig, Hanne

    1986-01-01

    We have cloned and sequenced a single copy gene encoding a ribosomal protein from the ciliate Tetrahymena thermophila. The gene product was identified as ribosomal protein S25 by comparison of the migration in two-dimensional polyacrylamide gels of the protein synthesized by translation in vitro...

  3. Gene regulation in response to protein disulphide isomerase deficiency

    DEFF Research Database (Denmark)

    Nørgaard, Per; Tachibana, Christine; Bruun, Anette W

    2003-01-01

    We have examined the activities of promoters of a number of yeast genes encoding resident endoplasmic reticulum proteins, and found increased expression in a strain with severe protein disulphide isomerase deficiency. Serial deletion in the promoter of the MPD1 gene, which encodes a PDI1-homologu...... element. The sequence (GACACG) does not resemble the unfolded protein response element. It is present in the upstream regions of the MPD1, MPD2, KAR2, PDI1 and ERO1 genes....

  4. The sulfolobicin genes of Sulfolobus acidocaldarius encode novel antimicrobial proteins.

    Science.gov (United States)

    Ellen, Albert F; Rohulya, Olha V; Fusetti, Fabrizia; Wagner, Michaela; Albers, Sonja-Verena; Driessen, Arnold J M

    2011-09-01

    Crenarchaea, such as Sulfolobus acidocaldarius and Sulfolobus tokodaii, produce antimicrobial proteins called sulfolobicins. These antimicrobial proteins inhibit the growth of closely related species. Here we report the identification of the sulfolobicin-encoding genes in S. acidocaldarius. The active sulfolobicin comprises two proteins that are equipped with a classical signal sequence. These proteins are secreted by the cells and found to be membrane vesicle associated. Gene inactivation studies demonstrate that both proteins are required for the bacteriostatic antimicrobial activity. Sulfolobicins constitute a novel class of antimicrobial proteins without detectable homology to any other protein.

  5. The Sulfolobicin Genes of Sulfolobus acidocaldarius Encode Novel Antimicrobial Proteins

    NARCIS (Netherlands)

    Ellen, Albert F.; Rohulya, Olha V.; Fusetti, Fabrizia; Wagner, Michaela; Albers, Sonja-Verena; Driessen, Arnold J. M.

    2011-01-01

    Crenarchaea, such as Sulfolobus acidocaldarius and Sulfolobus tokodaii, produce antimicrobial proteins called sulfolobicins. These antimicrobial proteins inhibit the growth of closely related species. Here we report the identification of the sulfolobicin-encoding genes in S. acidocaldarius. The acti

  6. 桃果实中脱落酸受体ABAR/CHLH结合区蛋白的原核表达、纯化及复性%Prokaryotic expression, purification, and renaturation of abscisi acid-binding protein ABAR/CHLH from peach fruit

    Institute of Scientific and Technical Information of China (English)

    刘青; 董银行; 卢冬; 李春丽; 沈元月

    2011-01-01

    为了剖析桃果实中脱落酸受体ABAR/CHLH蛋白的结合活性,从桃果实中提取总RNA,采用RT-PCR方法,以桃果实RNA逆转录的cDNA为模板,扩增出ABAR/CHLH基因的结合区功能片段C369,回收目的片段并测序,基因片段长度为1 121 bp,编码369个氨基酸残基,分子量约为40 kD.利用BamH Ⅰ和Not I酶切位点将该片段编码区插入原核表达载体pET-28a(+)中,构建ABAR/CHLH基因片段原核表达载体pET28a-C369,经菌落PCR和测序确证后,转化E.coli Rosetta(DE3),通过IPTG诱导其表达His-CHLH融合蛋白.通过SDS-PAGE检测及Ni-NTA琼脂糖树脂亲和层析柱纯化目的蛋白,并用纯化复性的His-CHLH C369融合蛋白制备抗体.%To detect the binding activity of ABA receptor ABAR/CHLH in peach, total RNA was extracted from young fruits of Prunus persica. The ABAR/CHLH gene was isolated by RT-PCR using cDNA synthesized from total RNA. The amplified fragment was sequenced to be 1121bp with 369 amino acid residues. This coding sequence was cloned into pET-28a ( + ) expression vector. The expression plasmid pET28a-C369 was transformed into E. Coli Rosetta (DE3) and expressed in E. Coli cells induced by the IPTG. SDS-PAGE analysis revealed that the His-CHLH fusion protein was highly expressed in E. Coli Rosetta (DE3). After purified by Ni-NTA affinity chromatography, the purified protein was successful renaturation, which laid the basis of studying the biological activities related to the protein.

  7. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.

    Science.gov (United States)

    Zahid, Henna; Miah, Layeque; Lau, Andy M; Brochard, Lea; Hati, Debolina; Bui, Tam T T; Drake, Alex F; Gor, Jayesh; Perkins, Stephen J; McDermott, Lindsay C

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.

  8. SNBRFinder: A Sequence-Based Hybrid Algorithm for Enhanced Prediction of Nucleic Acid-Binding Residues.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Yang

    Full Text Available Protein-nucleic acid interactions are central to various fundamental biological processes. Automated methods capable of reliably identifying DNA- and RNA-binding residues in protein sequence are assuming ever-increasing importance. The majority of current algorithms rely on feature-based prediction, but their accuracy remains to be further improved. Here we propose a sequence-based hybrid algorithm SNBRFinder (Sequence-based Nucleic acid-Binding Residue Finder by merging a feature predictor SNBRFinderF and a template predictor SNBRFinderT. SNBRFinderF was established using the support vector machine whose inputs include sequence profile and other complementary sequence descriptors, while SNBRFinderT was implemented with the sequence alignment algorithm based on profile hidden Markov models to capture the weakly homologous template of query sequence. Experimental results show that SNBRFinderF was clearly superior to the commonly used sequence profile-based predictor and SNBRFinderT can achieve comparable performance to the structure-based template methods. Leveraging the complementary relationship between these two predictors, SNBRFinder reasonably improved the performance of both DNA- and RNA-binding residue predictions. More importantly, the sequence-based hybrid prediction reached competitive performance relative to our previous structure-based counterpart. Our extensive and stringent comparisons show that SNBRFinder has obvious advantages over the existing sequence-based prediction algorithms. The value of our algorithm is highlighted by establishing an easy-to-use web server that is freely accessible at http://ibi.hzau.edu.cn/SNBRFinder.

  9. Regulation of human protein S gene (PROS1) transcription

    NARCIS (Netherlands)

    Wolf, Cornelia de

    2006-01-01

    This thesis describes the investigation of the transcriptional regulation of the gene for anticoagulant plasma Protein S, PROS1. Protein S is a cofactor for Protein C in the Protein C anticoagulant pathway. The coagulation cascade is negatively regulated by this pathway through inactivation of activ

  10. Gene Expression Profile Differences in Gastric Cancer and Normal Gastric Mucosa by Oligonucleotide Microarrays

    Institute of Scientific and Technical Information of China (English)

    Chuanding Yu; Shenhua Xu; HangZhou Mou; Zhiming Jiang; Chihong Zhu; Xianglin Liu

    2006-01-01

    OBJECTIVE To study the difference of gene expression in gastric cancer (T) and normal tissue of gastric mucosa (C), and to screen for associated novel genes in gastric cancers by oligonucleotide microarrays.METHODS U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T and C. Bioinformatics was used to analyze the detected results.RESULTS When gastric cancers were compared with normal gastric mucosa, a total of 270 genes were found with a difference of more than 9times in expression levels. Of the 270 genes, 157 were up-regulated (Signal Log Ratio [SLR] ≥3), and 113 were down-regulated (SLR ≤-3).Using a classification of function, the highest number of gene expression differences related to enzymes and their regulatory genes (67, 24.8%),followed by signal-transduction genes (43,15.9%). The third were nucleic acid binding genes (17, 6.3%), fourth were transporter genes (15, 5.5%)and fifth were protein binding genes (12, 4.4%). In addition there were 50genes of unknown function, accounting for 18.5%. The five above mentioned groups made up 56.9% of the total gene number.CONCLUSION The 5 gene groups (enzymes and their regulatory proteins, signal transduction proteins, nucleic acid binding proteins, transporter and protein binding) were abnormally expressed and are important genes for further study in gastric cancers.

  11. Binary gene induction and protein expression in individual cells

    Directory of Open Access Journals (Sweden)

    Conolly Rory B

    2006-04-01

    Full Text Available Abstract Background Eukaryotic gene transcription is believed to occur in either a binary or a graded fashion. With binary induction, a transcription activator (TA regulates the probability with which a gene template is switched from the inactive to the active state without affecting the rate at which RNA molecules are produced from the template. With graded, also called rheostat-like, induction the gene template has continuously varying levels of transcriptional activity, and the TA regulates the rate of RNA production. Support for each of these two mechanisms arises primarily from experimental studies measuring reporter proteins in individual cells, rather than from direct measurement of induction events at the gene template. Methods and results In this paper, using a computational model of stochastic gene expression, we have studied the biological and experimental conditions under which a binary induction mode operating at the gene template can give rise to differentially expressed "phenotypes" (i.e., binary, hybrid or graded at the protein level. We have also investigated whether the choice of reporter genes plays a significant role in determining the observed protein expression patterns in individual cells, given the diverse properties of commonly-used reporter genes. Our simulation confirmed early findings that the lifetimes of active/inactive promoters and half-lives of downstream mRNA/protein products are important determinants of various protein expression patterns, but showed that the induction time and the sensitivity with which the expressed genes are detected are also important experimental variables. Using parameter conditions representative of reporter genes including green fluorescence protein (GFP and β-galactosidase, we also demonstrated that graded gene expression is more likely to be observed with GFP, a longer-lived protein with low detection sensitivity. Conclusion The choice of reporter genes may determine whether protein

  12. Mosaic tetracycline resistance genes encoding ribosomal protection proteins.

    Science.gov (United States)

    Warburton, Philip J; Amodeo, Nina; Roberts, Adam P

    2016-12-01

    First reported in 2003, mosaic tetracycline resistance genes are a subgroup of the genes encoding ribosomal protection proteins (RPPs). They are formed when two or more RPP-encoding genes recombine resulting in a functional chimera. To date, the majority of mosaic genes are derived from sections of three RPP genes, tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this first review of mosaic genes, we report on their structure, diversity and prevalence, and suggest that these genes may be responsible for an under-reported contribution to tetracycline resistance in bacteria.

  13. Operon Gene Order Is Optimized for Ordered Protein Complex Assembly.

    Science.gov (United States)

    Wells, Jonathan N; Bergendahl, L Therese; Marsh, Joseph A

    2016-02-02

    The assembly of heteromeric protein complexes is an inherently stochastic process in which multiple genes are expressed separately into proteins, which must then somehow find each other within the cell. Here, we considered one of the ways by which prokaryotic organisms have attempted to maximize the efficiency of protein complex assembly: the organization of subunit-encoding genes into operons. Using structure-based assembly predictions, we show that operon gene order has been optimized to match the order in which protein subunits assemble. Exceptions to this are almost entirely highly expressed proteins for which assembly is less stochastic and for which precisely ordered translation offers less benefit. Overall, these results show that ordered protein complex assembly pathways are of significant biological importance and represent a major evolutionary constraint on operon gene organization.

  14. Expression of protein-coding genes embedded in ribosomal DNA

    DEFF Research Database (Denmark)

    Johansen, Steinar D; Haugen, Peik; Nielsen, Henrik

    2007-01-01

    Ribosomal DNA (rDNA) is a specialised chromosomal location that is dedicated to high-level transcription of ribosomal RNA genes. Interestingly, rDNAs are frequently interrupted by parasitic elements, some of which carry protein genes. These are non-LTR retrotransposons and group II introns...... that encode reverse transcriptase-like genes, and group I introns and archaeal introns that encode homing endonuclease genes (HEGs). Although rDNA-embedded protein genes are widespread in nuclei, organelles and bacteria, there is surprisingly little information available on how these genes are expressed....... Exceptions include a handful of HEGs from group I introns. Recent studies have revealed unusual and essential roles of group I and group I-like ribozymes in the endogenous expression of HEGs. Here we discuss general aspects of rDNA-embedded protein genes and focus on HEG expression from group I introns...

  15. Comparison of the Folding Mechanism of Highly Homologous Proteins in the Lipid-binding Protein Family

    Science.gov (United States)

    The folding mechanism of two closely related proteins in the intracellular lipid binding protein family, human bile acid binding protein (hBABP) and rat bile acid binding protein (rBABP) were examined. These proteins are 77% identical (93% similar) in sequence Both of these singl...

  16. The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution.

    Directory of Open Access Journals (Sweden)

    Jean-François Gout

    2010-05-01

    Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.

  17. Prioritization of candidate genes for cattle reproductive traits, based on protein-protein interactions, gene expression, and text-mining

    DEFF Research Database (Denmark)

    Hulsegge, Ina; Woelders, Henri; Smits, Mari;

    2013-01-01

    and processes in brain areas and pituitary involved in reproductive traits in cattle using information derived from three different data sources: gene expression, protein-protein interactions, and literature. We identified 59, 89, 53, 23, and 71 genes in bovine amygdala, dorsal hypothalamus, hippocampus...

  18. Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

    Full Text Available Abstract Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene

  19. Coevolution of gene expression among interacting proteins

    OpenAIRE

    2004-01-01

    Physically interacting proteins or parts of proteins are expected to evolve in a coordinated manner that preserves proper interactions. Such coevolution at the amino acid-sequence level is well documented and has been used to predict interacting proteins, domains, and amino acids. Interacting proteins are also often precisely coexpressed with one another, presumably to maintain proper stoichiometry among interacting components. Here, we show that the expression levels of physically inter...

  20. In Vitro bile acid binding of kale, mustard greens, broccoli, cabbage and green bell pepper improves with microwave cooking

    Science.gov (United States)

    Bile acid binding potential of foods and food fractions has been related to lowering the risk of heart disease and that of cancer. Sautéing or steam cooking has been observed to significantly improve bile acid binding of green/leafy vegetables. It was hypothesized that microwave cooking could impr...

  1. Conservation of ribosomal protein gene ordering in 16 complete genomes

    Institute of Scientific and Technical Information of China (English)

    王宁; 陈润生; 王永雄

    2000-01-01

    The organization of ribosomal proteins in 16 prokaryotic genomes was studied as an example of comparative genome analyses of gene systems. Hypothetical ribosomal protein-containing operons were constructed. These operons also contained putative genes and other non-ribosomal genes. The correspondences among these genes across different organisms were clarified by sequence homology computations. In this way a cross tabulation of 70 ribosomal proteins genes was constructed. On average, these were organized into 9-14 operons in each genome. There were also 25 non-ribosomal or putative genes in these mainly ribosomal protein operons. Hence the table contains 95 genes in total. It was found that: (i) the conservation of the block of about 20 r-proteins in the L3 and L4 operons across almost the entire eubacteria and ar-chaebacteria is remarkable; (ii) some operons only belong to eubacteria or archaebacte-ria; (iii) although the ribosomal protein operons are highly conserved within domain, there are fine variat

  2. Conservation of ribosomal protein gene ordering in 16 complete genomes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The organization of ribosomal proteins in 16 prokaryotic genomes was studied as an example of comparative genome analyses of gene systems. Hypothetical ribosomal protein-containing operons were constructed. These operons also contained putative genes and other non-ribosomal genes. The correspondences among these genes across different organisms were clarified by sequence homology computations. In this way a cross tabulation of 70 ribosomal proteins genes was constructed. On average, these were organized into 9-14 operons in each genome. There were also 25 non-ribosomal or putative genes in these mainly ribosomal protein operons. Hence the table contains 95 genes in total. It was found that: (i) the conservation of the block of about 20 r-proteins in the L3 and L4 operons across almost the entire eubacteria and archaebacteria is remarkable; (ii) some operons only belong to eubacteria or archaebacteria; (iii) although the ribosomal protein operons are highly conserved within domain, there are fine variations in some operons across different organisms within each domain, and these variations are informative on the evolutionary relations among the organisms. This method provides a new potential for studying the origin and evolution of old species.

  3. Selection for Genes Encoding Secreted Proteins and Receptors

    Science.gov (United States)

    Klein, Robert D.; Gu, Qimin; Goddard, Audrey; Rosenthal, Arnon

    1996-07-01

    Extracellular proteins play an essential role in the formation, differentiation, and maintenance of multicellular organisms. Despite that, the systematic identification of genes encoding these proteins has not been possible. We describe here a highly efficient method to isolate genes encoding secreted and membrane-bound proteins by using a single-step selection in yeast. Application of this method, termed signal peptide selection, to various tissues yielded 559 clones that appear to encode known or novel extracellular proteins. These include members of the transforming growth factor and epidermal growth factor protein families, endocrine hormones, tyrosine kinase receptors, serine/threonine kinase receptors, seven transmembrane receptors, cell adhesion molecules, extracellular matrix proteins, plasma proteins, and ion channels. The eventual identification of most, or all, extracellular signaling molecules will advance our understanding of fundamental biological processes and our ability to intervene in disease states.

  4. The KP4 killer protein gene family

    Science.gov (United States)

    Killer protein 4 (KP4) is a well studied toxin secreted by the maize smut fungus Ustilago maydis that kills sensitive Ustilago strains as well as inhibits Fusarium and plant root growth. This small, cysteine rich protein is encoded by a virus that depends on host survival for replication. KP4 functi...

  5. Associating genes and protein complexes with disease via network propagation.

    Directory of Open Access Journals (Sweden)

    Oron Vanunu

    2010-01-01

    Full Text Available A fundamental challenge in human health is the identification of disease-causing genes. Recently, several studies have tackled this challenge via a network-based approach, motivated by the observation that genes causing the same or similar diseases tend to lie close to one another in a network of protein-protein or functional interactions. However, most of these approaches use only local network information in the inference process and are restricted to inferring single gene associations. Here, we provide a global, network-based method for prioritizing disease genes and inferring protein complex associations, which we call PRINCE. The method is based on formulating constraints on the prioritization function that relate to its smoothness over the network and usage of prior information. We exploit this function to predict not only genes but also protein complex associations with a disease of interest. We test our method on gene-disease association data, evaluating both the prioritization achieved and the protein complexes inferred. We show that our method outperforms extant approaches in both tasks. Using data on 1,369 diseases from the OMIM knowledgebase, our method is able (in a cross validation setting to rank the true causal gene first for 34% of the diseases, and infer 139 disease-related complexes that are highly coherent in terms of the function, expression and conservation of their member proteins. Importantly, we apply our method to study three multi-factorial diseases for which some causal genes have been found already: prostate cancer, alzheimer and type 2 diabetes mellitus. PRINCE's predictions for these diseases highly match the known literature, suggesting several novel causal genes and protein complexes for further investigation.

  6. Obstructive Sleep Apena Hypopnea Syndrome in Relation to Serum Adipocyte Fatty Acid-Binding Protein:A Comparative Study between Xinjiang Uygur and Han Ethnic Groups%新疆维汉民族阻塞性睡眠呼吸暂停低通气综合征患者血清脂肪细胞型脂肪酸结合蛋白水平比较研究

    Institute of Scientific and Technical Information of China (English)

    夏宇; 武玉刚; 哈依努尔; 胡昕; 叶红

    2012-01-01

    Objective To investigate the relation between obstructive sleep apnea hypopnea syndrome ( OSAHS ) and fasting serum adipocyte fatty - acid binding protein (A - FABP ) in Xinjiang Uygur and Han ethnic groups. Methods A total of 120 ( 60 from each ethnic group ) male patients were randomly selected from those diagnosed as having OSAHS by polysomnogra-phy ( PSG ) in our hospital. Another 104 men ( 52 from each ethnic group ) without OSAHS were randomly selected as the control groups from the health checkup subjects. The serum A - FABP level of subjects in the four groups was measured with ELISA. Results The serum A - FABP level of OSAHS patients was positively correlated with the neck circumference, waist circumference , abdominal circumference, apnea hypopnea index ( AHI ), body mass index ( BMI ), and the longest apnea time ( Tmax ) ( P <0. 01 ), and was negatively correlated with the lowest oxygen saturation ( LSaO2 ) ( P <0. 01 ). The BMI and A - FABP of the OSAHS patients were higher than that of the subjects in the control groups ( P < 0. 05 ). The serum A - FABP level of the OSAHS patients in Uygur group was significantly higher than that of the Han group ( P < 0. 01 ). Conclusion OSAHS may cause the increase of fasting serum A - FABP. Further studies are needed to investigate the discrepancy of fasting serum A - FABP levels of Uygur and Han OSAHS patients.%目的 探讨新疆维汉民族阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者空腹血清脂肪细胞型脂肪酸结合蛋白(A-FABP)水平变化.方法 采取完全随机方法抽取经多道睡眠描记术(PSG)监测确诊为OSAHS的维族及汉族患者各60例,并选取维族及汉族各52例健康体检者作为对照组,测定两组血清A-FABP水平及其他指标.结果 OSAHS患者的血清A-FABP水平与其颈围、腰围、腹围、睡眠呼吸暂停低通气指数(AHI)、体质指数(BMI)、最长呼吸暂停时间均呈正相关(P<0.01),与最低血氧饱和度呈负相关(P<0

  7. Molecular quantification of genes encoding for green-fluorescent proteins

    DEFF Research Database (Denmark)

    Felske, A; Vandieken, V; Pauling, B V

    2003-01-01

    A quantitative PCR approach is presented to analyze the amount of recombinant green fluorescent protein (gfp) genes in environmental DNA samples. The quantification assay is a combination of specific PCR amplification and temperature gradient gel electrophoresis (TGGE). Gene quantification is pro...

  8. Selection on protein-coding genes of natural cyanobacterial populations

    NARCIS (Netherlands)

    Mes, T.H.M.; Doeleman, M.W.; Lodders, N.; Nübel, U.; Stal, L.J.

    2006-01-01

    We examined the distribution of synonymous and non-synonymous changes in 12 protein-coding genes of natural populations of cyanobacteria to infer changes in gene functionality. By comparing mutation distributions within and across species using the McDonald–Kreitman test, we found data sets to conta

  9. Rare disease relations through common genes and protein interactions.

    Science.gov (United States)

    Fernandez-Novo, Sara; Pazos, Florencio; Chagoyen, Monica

    2016-06-01

    ODCs (Orphan Disease Connections), available at http://csbg.cnb.csic.es/odcs, is a novel resource to explore potential molecular relations between rare diseases. These molecular relations have been established through the integration of disease susceptibility genes and human protein-protein interactions. The database currently contains 54,941 relations between 3032 diseases.

  10. Prediction of human protein function according to Gene Ontology categories

    DEFF Research Database (Denmark)

    Jensen, Lars Juhl; Gupta, Ramneek; Stærfeldt, Hans Henrik;

    2003-01-01

    developed a method for prediction of protein function for a subset of classes from the Gene Ontology classification scheme. This subset includes several pharmaceutically interesting categories-transcription factors, receptors, ion channels, stress and immune response proteins, hormones and growth factors...

  11. Kinetics of fatty acid binding ability of glycated human serum albumin

    Indian Academy of Sciences (India)

    Eiji Yamazaki; Minoru Inagaki; Osamu Kurita; Tetsuji Inoue

    2005-09-01

    Kinetics of fatty acid binding ability of glycated human serum albumin (HSA) were investigated by fluorescent displacement technique with 1-anilino-8-naphtharene sulphonic acid (ANS method), and photometric detection of nonesterified-fatty-acid (NEFA method). Changing of binding affinities of glycated HSA toward oleic acid, linoleic acid, lauric acid, and caproic acid, were not observed by the ANS method. However, decreases of binding capacities after 55 days glycation were confirmed by the NEFA method in comparison to control HSA. The decrease in binding affinities was: oleic acid (84%), linoleic acid (84%), lauric acid (87%), and caproic acid (90%), respectively. The decreases were consistent with decrease of the intact lysine residues in glycated HSA. The present observation indicates that HSA promptly loses its binding ability to fatty acid as soon as the lysine residues at fatty acid binding sites are glycated.

  12. Mesangial cell-derived tumor necrosis factor α up-regulates the expression of tubular liver type fatty acid binding-protein and its renoprotective role in IgA nephropathy%系膜细胞源性肿瘤坏死因子α上调IgA肾病肾小管肝型脂肪酸结合蛋白的表达及其肾脏保护作用

    Institute of Scientific and Technical Information of China (English)

    佐楠; 栗霄立; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    Objective To explore the mechanism of up-regulation of tubular liver-type fatty acid binding-protein (L-FABP) in IgA nephropathy (IgAN) and its renoprotective role.Methods Murine mesangial cells (MCs) from primary cell culture were cultured with aggregated IgA (AIgA) (10 to 250 mg/L) for 48 hours. The supernatant after culture was collected as AIgA-MC medium. Murine proximal tubular cell line (mProx) stably expressing human L-FABP (hL-FABP) by transfection (mProx-L) were cultured with AIgA, AIgA-MC medium and /or neutralizing anti-TNF-α antibody and recombinant murine TNF-α, respectively. AIgA-MC medium (AIgA final concentration was 25 mg/L) was cultured with mProx and mProx-L cells. The mRNA expressions of hL-FABP and MCP-1 of the cells were detected by real-time PCR. The protein expressions of hL-FABP and 4-HNE of the cells were detected by Western blotting. Results (1) The hL-FABP mRNA and protein expression stimulated by AIgA-MC medium was significantly higher as compared to AIgA (P<0.01). (2) Pre-incubation of neutralizing anti-TNF-α antibody (final concentration was 1 and 5 mg/L) with mProx-L cells could significantly suppress the up-regulation of hL-FABP protein expression induced by AlgA-MC medium (P<0.05 and P<0.01).(3) Recombinant murine TNF-α (final concentration was 50 and 250 ng/L) also induced a significant up-regulation of hL-FABP expression (P<0.01). (4) After the stimulation of AIgA-MC medium, both 4-HNE protein expression and MCP-1 mRNA expression were significantly suppressed in mProx-L cells compared to those of mProx cells (P <0.05 and P<0.01). Conclusion Mesangial cell-derived TNF-α can induce up-regulation of tubular L-FABP expression. Overexpression of tubular L-FABP may lessen the progression of IgAN by reducing oxidative stress and inflammatory mediators.%目的 探讨体外近曲小管肝型脂肪酸结合蛋白(L-FABP)在IgA肾病(IgAN)中的上调机制及其对肾脏的保护作用.方法 原代培养的小鼠系膜

  13. Effects of mutations in the Arabidopsis Cold Shock Domain Protein 3 (AtCSP3) gene on leaf cell expansion.

    Science.gov (United States)

    Yang, Yongil; Karlson, Dale

    2012-08-01

    The cold shock domain is among the most evolutionarily conserved nucleic acid binding domains from prokaryotes to higher eukaryotes, including plants. Although eukaryotic cold shock domain proteins have been extensively studied as transcriptional and post-transcriptional regulators during various developmental processes, their functional roles in plants remains poorly understood. In this study, AtCSP3 (At2g17870), which is one of four Arabidopsis thaliana c old s hock domain proteins (AtCSPs), was functionally characterized. Quantitative RT-PCR analysis confirmed high expression of AtCSP3 in reproductive and meristematic tissues. A homozygous atcsp3 loss-of-function mutant exhibits an overall reduced seedling size, stunted and orbicular rosette leaves, reduced petiole length, and curled leaf blades. Palisade mesophyll cells are smaller and more circular in atcsp3 leaves. Cell size analysis indicated that the reduced size of the circular mesophyll cells appears to be generated by a reduction of cell length along the leaf-length axis, resulting in an orbicular leaf shape. It was also determined that leaf cell expansion is impaired for lateral leaf development in the atcsp3 loss-of-function mutant, but leaf cell proliferation is not affected. AtCSP3 loss-of-function resulted in a dramatic reduction of LNG1 transcript, a gene that is involved in two-dimensional leaf polarity regulation. Transient subcellular localization of AtCSP3 in onion epidermal cells confirmed a nucleocytoplasmic localization pattern. Collectively, these data suggest that AtCSP3 is functionally linked to the regulation of leaf length by affecting LNG1 transcript accumulation during leaf development. A putative function of AtCSP3 as an RNA binding protein is also discussed in relation to leaf development.

  14. Analysis of gene and protein name synonyms in Entrez Gene and UniProtKB resources

    KAUST Repository

    Arkasosy, Basil

    2013-05-11

    Ambiguity in texts is a well-known problem: words can carry several meanings, and hence, can be read and interpreted differently. This is also true in the biological literature; names of biological concepts, such as genes and proteins, might be ambiguous, referring in some cases to more than one gene or one protein, or in others, to both genes and proteins at the same time. Public biological databases give a very useful insight about genes and proteins information, including their names. In this study, we made a thorough analysis of the nomenclatures of genes and proteins in two data sources and for six different species. We developed an automated process that parses, extracts, processes and stores information available in two major biological databases: Entrez Gene and UniProtKB. We analysed gene and protein synonyms, their types, frequencies, and the ambiguities within a species, in between data sources and cross-species. We found that at least 40% of the cross-species ambiguities are caused by names that are already ambiguous within the species. Our study shows that from the six species we analysed (Homo Sapiens, Mus Musculus, Arabidopsis Thaliana, Oryza Sativa, Bacillus Subtilis and Pseudomonas Fluorescens), rice (Oriza Sativa) has the best naming model in Entrez Gene database, with low ambiguities between data sources and cross-species.

  15. Locus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network.

    Science.gov (United States)

    Keith, Benjamin P; Robertson, David L; Hentges, Kathryn E

    2014-01-01

    Mutations in genes potentially lead to a number of genetic diseases with differing severity. These disease genes have been the focus of research in recent years showing that the disease gene population as a whole is not homogeneous, and can be categorized according to their interactions. Locus heterogeneity describes a single disorder caused by mutations in different genes each acting individually to cause the same disease. Using datasets of experimentally derived human disease genes and protein interactions, we created a protein interaction network to investigate the relationships between the products of genes associated with a disease displaying locus heterogeneity, and use network parameters to suggest properties that distinguish these disease genes from the overall disease gene population. Through the manual curation of known causative genes of 100 diseases displaying locus heterogeneity and 397 single-gene Mendelian disorders, we use network parameters to show that our locus heterogeneity network displays distinct properties from the global disease network and a Mendelian network. Using the global human proteome, through random simulation of the network we show that heterogeneous genes display significant interconnectivity. Further topological analysis of this network revealed clustering of locus heterogeneity genes that cause identical disorders, indicating that these disease genes are involved in similar biological processes. We then use this information to suggest additional genes that may contribute to diseases with locus heterogeneity.

  16. Ribosomal protein gene knockdown causes developmental defects in zebrafish.

    Directory of Open Access Journals (Sweden)

    Tamayo Uechi

    Full Text Available The ribosomal proteins (RPs form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases.

  17. X-ray structure of Pur-alpha reveals a Whirly-like fold and an unusual nucleic-acid binding surface.

    Science.gov (United States)

    Graebsch, Almut; Roche, Stéphane; Niessing, Dierk

    2009-11-03

    The PUR protein family is a distinct and highly conserved class that is characterized by its sequence-specific RNA- and DNA-binding. Its best-studied family member, Pur-alpha, acts as a transcriptional regulator, as host factor for viral replication, and as cofactor for mRNP localization in dendrites. Pur-alpha-deficient mice show severe neurologic defects and die after birth. Nucleic-acid binding by Pur-alpha is mediated by its central core region, for which no structural information is available. We determined the x-ray structure of residues 40 to 185 from Drosophila melanogaster Pur-alpha, which constitutes a major part of the core region. We found that this region contains two almost identical structural motifs, termed "PUR repeats," which interact with each other to form a PUR domain. DNA- and RNA-binding studies confirmed that PUR domains are indeed functional nucleic-acid binding domains. Database analysis show that PUR domains share a fold with the Whirly class of nucleic-acid binding proteins. Structural analysis combined with mutational studies suggest that a PUR domain binds nucleic acids through two independent surface regions involving concave beta-sheets. Structure-based sequence alignment revealed that the core region harbors a third PUR repeat at its C terminus. Subsequent characterization by small-angle x-ray scattering (SAXS) and size-exclusion chromatography indicated that PUR repeat III mediates dimerization of Pur-alpha. Surface envelopes calculated from SAXS data show that the Pur-alpha dimer consisting of repeats I to III is arranged in a Z-like shape. This unexpected domain organization of the entire core domain of Pur-alpha has direct implications for ssDNA/ssRNA and dsDNA binding.

  18. Siglec-15, a member of the sialic acid-binding lectin, is a novel regulator for osteoclast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Hiruma, Yoshiharu, E-mail: hiruma.yoshiharu.hy@daiichisankyo.co.jp [Biological Research Laboratories, Daiichi Sankyo Co. Ltd., Tokyo 134-8630 (Japan); Hirai, Takehiro [Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Co. Ltd., Tokyo 134-8630 (Japan); Tsuda, Eisuke [Biological Research Laboratories, Daiichi Sankyo Co. Ltd., Tokyo 134-8630 (Japan)

    2011-06-10

    Highlights: {yields} Siglec-15 was identified as a gene overexpressed in giant cell tumor. {yields} Siglec-15 mRNA expression increased in association with osteoclast differentiation. {yields} Polyclonal antibody to Siglec-15 inhibited osteoclast differentiation in vitro. -- Abstract: Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells derived from monocyte/macrophage-lineage precursors and are critically responsible for bone resorption. In giant cell tumor of bone (GCT), numerous TRAP-positive multinucleated giant cells emerge and severe osteolytic bone destruction occurs, implying that the emerged giant cells are biologically similar to osteoclasts. To identify novel genes involved in osteoclastogenesis, we searched genes whose expression pattern was significantly different in GCT from normal and other bone tumor tissues. By screening a human gene expression database, we identified sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) as one of the genes markedly overexpressed in GCT. The mRNA expression level of Siglec-15 increased in association with osteoclast differentiation in cultures of mouse primary unfractionated bone marrow cells (UBMC), RAW264.7 cells of the mouse macrophage cell line and human osteoclast precursors (OCP). Treatment with polyclonal antibody to mouse Siglec-15 markedly inhibited osteoclast differentiation in primary mouse bone marrow monocyte/macrophage (BMM) cells stimulated with receptor activator of nuclear factor {kappa}B ligand (RANKL) or tumor necrosis factor (TNF)-{alpha}. The antibody also inhibited osteoclast differentiation in cultures of mouse UBMC and RAW264.7 cells stimulated with active vitamin D{sub 3} and RANKL, respectively. Finally, treatment with polyclonal antibody to human Siglec-15 inhibited RANKL-induced TRAP-positive multinuclear cell formation in a human OCP culture. These results suggest that Siglec-15 plays an important role in osteoclast differentiation.

  19. Expression of genes encoding extracellular matrix proteins: a macroarray study.

    Science.gov (United States)

    Futyma, Konrad; Miotła, Paweł; Różyńska, Krystyna; Zdunek, Małgorzata; Semczuk, Andrzej; Rechberger, Tomasz; Wojcierowski, Jacek

    2014-12-01

    Endometrial cancer (EC) is one of the most common gynecological malignancies in Poland, with well-established risk factors. Genetic instability and molecular alterations responsible for endometrial carcinogenesis have been systematically investigated. The aim of the present study was to investigate, by means of cDNA macroarrays, the expression profiles of genes encoding extracellular matrix (ECM) proteins in ECs. Tissue specimens were collected during surgical procedures from 40 patients with EC, and control tissue was collected from 9 patients with uterine leiomyomas. RNA was isolated and RT-PCR with radioisotope-labeled cDNA was performed. The levels of ECM protein gene expression in normal endometrial tissues were compared to the expression of these genes in EC specimens. Statistically significant differences in gene expression, stratified by clinical stage of the ECs, were detected for aggrecan, vitronectin, tenascin R, nidogen and two collagen proteins: type VIII chain α1 and type XI chain α2. All of these proteins were overexpressed in stage III endometrial carcinomas compared to levels in stage I and II uterine neoplasms. In conclusion, increased expression of genes encoding ECM proteins may play an important role in facilitating accelerated disease progression of human ECs.

  20. 肾小管肝型脂肪酸结合蛋白对小鼠IgA肾病的肾脏保护作用%Protective effects of tubular liver-type fatty acid binding protein on murine IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    佐楠; 李艳秋; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    of hL-FABP, fibronectin (FN)and monocyte chemoattractant protein-1 (MCP-1) mRNA were detected by real-time PCR. hL-FABP,FN, type Ⅳ collagen (Col Ⅳ ), hemeoxygenase-1 (HO-1) and 4-hydroxy-2-nonenal (4-HNE)modified proteins were detected by Western blotting. The distribution of hL-FABP and FN protein in kidney was detected by immunohistochemistry. The level of serum IgA, urinary albumin and urinary hL-FABP was detected by ELISA. Results (1) IgAN was reconstituted in both Tg and WT mice by BMT: mesangial IgA deposition and up-regulation of serum IgA. The levels were not significantly different between two groups (Tg-ddY and WT-ddY). (2) hL-FABP was expressed in proximal tubular cells of normal Tg mice. The mRNA (1.62±0.32 vs 0.46±0.09, P<0.01) and protein expression (1.74±0.76 vs 1.14±0.31, P<0.01) of hL-FABP was up-regulated in Tg-ddY kidney and urinary hL-FABP level (μg/g creatinine) was significantly increased (59.87±26.75 vs 31.01±14.86, P<0.05) at the 6th week after BMT. (3) WT-ddY mice showed a significantly higher urinary albumin level (mg/L) (828±656 vs 82±22, P<0.01), severer mesangial matrix expansion (P<0.01),more glomerular FN and Col Ⅳ deposition at the 12th week. (4) Up-regulation of renal hL-FABP was associated with significant suppression of renal HO-1 expression (P <0.05),accumulation of 4-HNE modified proteins (P<0.05) and MCP-1 mRNA expression (P<0.01) in Tg-ddY mice. Conclusion Tubular L-FABP may lessen the progression of glomerular damage at early stages of IgAN by reducing oxidative stress and inflammatory mediators.

  1. Lists2Networks: Integrated analysis of gene/protein lists

    Directory of Open Access Journals (Sweden)

    Ma'ayan Avi

    2010-02-01

    Full Text Available Abstract Background Systems biologists are faced with the difficultly of analyzing results from large-scale studies that profile the activity of many genes, RNAs and proteins, applied in different experiments, under different conditions, and reported in different publications. To address this challenge it is desirable to compare the results from different related studies such as mRNA expression microarrays, genome-wide ChIP-X, RNAi screens, proteomics and phosphoproteomics experiments in a coherent global framework. In addition, linking high-content multilayered experimental results with prior biological knowledge can be useful for identifying functional themes and form novel hypotheses. Results We present Lists2Networks, a web-based system that allows users to upload lists of mammalian genes/proteins onto a server-based program for integrated analysis. The system includes web-based tools to manipulate lists with different set operations, to expand lists using existing mammalian networks of protein-protein interactions, co-expression correlation, or background knowledge co-annotation correlation, as well as to apply gene-list enrichment analyses against many gene-list libraries of prior biological knowledge such as pathways, gene ontology terms, kinase-substrate, microRNA-mRAN, and protein-protein interactions, metabolites, and protein domains. Such analyses can be applied to several lists at once against many prior knowledge libraries of gene-lists associated with specific annotations. The system also contains features that allow users to export networks and share lists with other users of the system. Conclusions Lists2Networks is a user friendly web-based software system expected to significantly ease the computational analysis process for experimental systems biologists employing high-throughput experiments at multiple layers of regulation. The system is freely available at http://www.lists2networks.org.

  2. The proteolipid protein gene: Double, double, . . . and trouble

    Energy Technology Data Exchange (ETDEWEB)

    Hodes, M.E.; Dlouhy, S.R. [Indiana Univ. School of Medicine, Indianapolis, IN (United States)

    1996-07-01

    That more of a good thing may be too much has been apparent at least since the discovery that Down syndrome is caused by three copies of chromosome 21 instead of the normal two. Duplications of myelin genes also lead to trouble. An extra dose of PMP22, the gene for a protein of peripheral nervous system myelin, causes Charcot-Marie Tooth type 1A disease (CMT1A). Increased dosage of the proteolipid protein gene, PLP, which encodes the chief protein of CNS myelin, can cause Pelizaeus-Merzbacher disease (PMD). The work of Inoue et al. is of particular importance because they found the duplication in four of five families with {open_quotes}classical{close_quotes} PMD, whereas other changes in PLP, such as missense mutations, are found in no more than one in four or five patients with the disease. 27 refs.

  3. Progress of animal FABP family genes and their association with fat deposition%动物FABP家族基因与脂肪沉积关联研究进展

    Institute of Scientific and Technical Information of China (English)

    刘顺德; 李娜; 高小艳; 刘文艳

    2010-01-01

    综述了动物FABP(Fatty acid binding protein,FABP)的类型、分布、结构特点与H-FABP(Hear fatty acid binding proteint,H-FABP),A-FABP(Adipocyte fatty acid binding protein, A-FABP),L-FABP(Live fatty acid binding protein,L-FABP),I-FABP(Ileum fatty acid binding protein,I-FABP),Ex-FABP(Extracellular fatty acidbinding protein,Ex-FABP)基因多态性及其与脂肪沉积的关联研究进展.

  4. NAM-1gene polymorphism and grain protein content in Hordeum.

    Science.gov (United States)

    Jamar, Catherine; Loffet, Francois; Frettinger, Patrick; Ramsay, Luke; Fauconnier, Marie-Laure; du Jardin, Patrick

    2010-04-15

    Grain protein content (GPC) is a key quality factor for malting and brewing process. In wheat, a QTL explaining a large part of GPC variation was identified, which co-localizes with a gene encoding a NAC transcription factor (TtNAM-B1). NAC transcription factors influence GPC by their role in the regulation of senescence and in protein remobilization. An orthologous gene was discovered on barley chromosome 6H where a GPC QTL was mapped. In this study, we identify allelic variation of the NAM-1 gene for three species of Hordeum representing wild and cultivated barley and we investigate the possible link with GPC. Three haplotypes were identified, one corresponds to the sequences of 11 European varieties representing H. vulgare, one corresponds to the sequence found in H. spontaneum and one represents the sequence of H. bulbosum. Three SNPs were identified between H. spontaneum sequence and H. vulgare sequence. One of the H. bulbosum polymorphisms leads to the introduction of a stop codon and a non-functional protein. Differences in GPC between the 11 varieties were found but no polymorphism in the NAM-1 gene was observed, suggesting that differences in expression of the HvNAM-1 gene or other genes should play a role in GPC regulation. Nevertheless based on published values for GPC of H. bulbosum and H. spontaneum compared to GPC measured here in H. vulgare, the non-functional protein is associated with the lower GPC, suggesting that loss of functionality of the NAM-1 gene in Hordeum is related to lower GPC. Moreover H. spontaneum GPC seems to be higher than H. vulgare GPC, suggesting also that allelic variation of the functional NAM-1 gene could be associated with GPC variation within the genus Hordeum.

  5. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

    Directory of Open Access Journals (Sweden)

    Baoman Wang

    2015-01-01

    Full Text Available Apoptosis is the process of programmed cell death (PCD that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature.

  6. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2017-03-21

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  7. Expression of a Carrot Antifreeze Protein Gene in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Ma Xinyu; Shen Xin; Lu Cunfu

    2003-01-01

    The recombinant expression vectorpET43. lb-AFP, which contains full encoding region of a carrot 36 kD antifreeze protein (AFP) gene was constructed. The recombinant was transformed into expression host carrying T7 RNA polymerase gene (DE3 lysogen) and induced by 1 mmol. L-1 IPTG (isopropyl-β-D-thiogalactoside) to express 110 kD polypeptide of AFP fusion protein.The analysis of product solubility revealed that pET43. 1b-AFP was predominately soluble, and the expressed amount reached the maximum after the IPTG treatment for 3 h.

  8. Use of Galerina marginata genes and proteins for peptide production

    Science.gov (United States)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  9. 川崎病心型脂肪酸结合蛋白及血小板活化因子的变化及临床意义%Serum heart-type fatty acid-binding protein and platelet activating factor levels in Kawasaki disease and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    洪泽; 孙兴珍

    2011-01-01

    46例川崎病患儿(观察组)根据超声心动图结果分为冠状动脉损伤(CAL)组19例和非冠状动脉损伤(NCAL)组27例,另选择正常健康者50例为对照组.检测所有对象的心型脂肪酸结合蛋白(h-FABP)、血小板活化因子(PAF)、肌钙蛋白Ⅰ及肌酸磷酸激酶同工酶等.结果显示,观察组h-FABP、肌钙蛋白Ⅰ水平和阳性率均显著高于对照组(P<0.05),两组间肌酸磷酸激酶同工酶水平和阳性率比较差异无统计学意义(P>0.05),观察组h-FABP阳性率显著高于肌钙蛋白Ⅰ和肌酸磷酸激酶同工酶阳性率(P<0.05),PAF水平及血小板、中性粒细胞计数显著高于对照组(P<0.05);CAL组h-FABP、PAF水平显著高于NCAL组(P<0.05).提示,h-FABP和PAF对预测川崎病患儿冠状动脉病变有重要的临床价值.%Forty six children with Kawasaki disease (observer group) were classified as coronary artery lesions (CAL) subgroup (19 cases) and non-coronary artery lesions (NCAL) subgroup (27 cases)according to echocardiography; 50 healthy children served as control group.Serum heart-type fatty acidbinding protein (h-FABP), platelet activating factor (PAF), cardiac tropnin Ⅰ (cTnI) and creatine kinase isoenzyme MB (CK-MB) levels of all subjects were detected.The results showed that the h-FABP and cTnI levels and positive rate in observer group were higher those in control group (P < 0.05 ), while there were no differences in CK-MB level and positive rate between two groups ( P > 0.05 ).The h-FABP positive rate in observation group was higher than the positive rates of cTnI and CK-MB (P <0.05).The PAF level, PLT and polymorphonuclear neutrophil count in observer group were higher than those in control group ( P <0.05).The h-FABP and PAF levels in CAL subgroup were higher than those in NCAL subgroup (P <0.05).The results suggest that serum h-FABP and PAF can be used as diagnostic indicators for Kawasaki disease complicated with coronary artery lesions.

  10. The Changes and Its Clinical Significance of Heart-type Fatty Acid-binding Protein Levels in Patients with Acute Pulmonary Embolism%肺栓塞患者心型脂肪酸结合蛋白水平的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    何磊; 魏庆民; 时秀华; 张春霞

    2012-01-01

    目的 探讨急性肺栓塞(APE)患者心型脂肪酸结合蛋白(H-FABP)浓度的变化及临床意义.方法 选择2009年8月至2011年12月在我院诊治的102例APE患者为观察组,同期选择年龄、性别匹配的健康体检者90例为对照组.采用双向侧流免疫法检测H-FABP浓度,比较两组血H-FABP水平以及观察组治疗前后血H-FABP水平、超声心动图、动脉血氧分压的差异.结果 观察组血H-FABP浓度为(6.95±4.80)μg/L,对照组为(4.97±2.77)μg/L,两组比较差异有统计学意义(P<0.01).APE患者治疗前后血H-FABP比较差异有统计学意义(P<0.01),APE患者治疗后右心室舒张末期内径缩小,肺动脉压力下降,动脉血氧分压升高,差异有统计学意义(P<0.01).结论 APE患者血H-FABP浓度升高,有效治疗后浓度下降,观察血H-FABP浓度变化有助于APE的诊断和疗效评估.%Objective To investigate the changes oi plasma heart-type iatty arid-binding protein ( H-FABP)and its rliniral significance in patients with acute pulmonary embolism( APE ). Methods 102 APE cases diagnosed and treated in our hospital during August 2009 to December 201 1 were chosen as the observation group, 90 healthy people of the matching age and gender ior healthy check-up were chosen as the control group. H-FABP concentration were measured by two-way flow immune method, H-FABP blood level was compared and the differences in H-FABP level, echocardiography, arterial oxygen tension before and after treatment were observed. Results The blood H-FABP concentration oi the observation group was( 6. 95 ± 4.80)μg/L,and was( 4. 97 ±2.77)μg/L of the control group,statistically significant differen(P <0. 01 ). H-FABP blood concentration before treatment and after treatment was signiiicantly different(P < 0. 01 ), the right ventricular end-diastolic diameter reduced,pulmonary artery pressure decreased,arterial oxygen pressure increased after treatment with statistical significance( P < 0. 01

  11. 卡维地洛与比索洛尔对心力衰竭患者心功能及心型脂肪结合蛋白、脑钠肽的影响%Effect of Carvedilol and Bisoprolol on the Changes of Heart Type Fatty Acid Binding Protein and Brain Natri-uretic Peptide in Patients with Congestive Heart Failure

    Institute of Scientific and Technical Information of China (English)

    张海涛; 邵辉; 王兴宏; 董秋立; 王忠明

    2015-01-01

    OBJECTIVE:To observe the changes of heart type fatty binding protein (H-FABP) and brain natriuretic peptide (BNP)when carvedilol and bisoprolol in the treatment of elderly patients with chronic heart failure(CHF). METHODS:110 CHF patients were randomly assigned into carvedilol group and bisoprolol group (n=55). Carvedilol group was given carvedilol 3.125 mg,bid,doubling dose every 2 weeks to reach target dose 25mg or maximum tolerant dose;bisoprolol group was given bisoprolol 1.25 mg,qd,doubling dose every 2 weeks to reach target dose 10 mg or maximum tolerant dose. Treatment course lasted for 6 months. Clinical effective rate of 2 groups were observed after treatment. Echocardiography was used to measure the changes of LVEDD,LVEF,SBP and DBP before and after treatment. The plasma concentration of BNP and H-FABP were measured by radio-immunoassay. RESULTS:After treatment,total effective rate of carvedilol group(96.4%)was higher than that of bisoprolol group (89.2%),with statistical significance(P<0.05). Compared with before treatment,the levels of LVEDD,LVEF,BNP,H-FABP, SBP and DBP in 2 groups were all decreased significantly after treatment,with statistical significance (P<0.01 or P<0.05). CON-CLUSIONS:Both carvedilol and bisoprolol can significantly improve cardiac function,but carvedilol efficacy is more significant. At the same time,significant decrease of H-FABP before and after treatment indicate that H-FABP can be used as a reliable index of heart failure treatment effect.%目的:观察卡维地洛与比索洛尔对老年心力衰竭(CHF)患者心功能及心型脂肪结合蛋白(H-FABP)、脑钠肽(BNP)水平的影响。方法:选取CHF患者110例,按随机数字表法分为卡维地洛组和比索洛尔组,各55例。卡维地洛组患者给予卡维地洛3.125 mg,bid,每2周剂量加倍,直至达目标靶剂量25 mg或耐受最大剂量;比索洛尔组患者给予比索洛尔1.25 mg,qd,每2周剂量加

  12. Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R. [Univ. of California, San Francisco, CA (United States)] [and others

    1994-09-01

    Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 gene region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.

  13. Developmentally distinct MYB genes encode functionally equivalent proteins in Arabidopsis.

    Science.gov (United States)

    Lee, M M; Schiefelbein, J

    2001-05-01

    The duplication and divergence of developmental control genes is thought to have driven morphological diversification during the evolution of multicellular organisms. To examine the molecular basis of this process, we analyzed the functional relationship between two paralogous MYB transcription factor genes, WEREWOLF (WER) and GLABROUS1 (GL1), in Arabidopsis. The WER and GL1 genes specify distinct cell types and exhibit non-overlapping expression patterns during Arabidopsis development. Nevertheless, reciprocal complementation experiments with a series of gene fusions showed that WER and GL1 encode functionally equivalent proteins, and their unique roles in plant development are entirely due to differences in their cis-regulatory sequences. Similar experiments with a distantly related MYB gene (MYB2) showed that its product cannot functionally substitute for WER or GL1. Furthermore, an analysis of the WER and GL1 proteins shows that conserved sequences correspond to specific functional domains. These results provide new insights into the evolution of the MYB gene family in Arabidopsis, and, more generally, they demonstrate that novel developmental gene function may arise solely by the modification of cis-regulatory sequences.

  14. Evolution of the MAGUK protein gene family in premetazoan lineages

    Directory of Open Access Journals (Sweden)

    Ruiz-Trillo Iñaki

    2010-04-01

    Full Text Available Abstract Background Cell-to-cell communication is a key process in multicellular organisms. In multicellular animals, scaffolding proteins belonging to the family of membrane-associated guanylate kinases (MAGUK are involved in the regulation and formation of cell junctions. These MAGUK proteins were believed to be exclusive to Metazoa. However, a MAGUK gene was recently identified in an EST survey of Capsaspora owczarzaki, an unicellular organism that branches off near the metazoan clade. To further investigate the evolutionary history of MAGUK, we have undertook a broader search for this gene family using available genomic sequences of different opisthokont taxa. Results Our survey and phylogenetic analyses show that MAGUK proteins are present not only in Metazoa, but also in the choanoflagellate Monosiga brevicollis and in the protist Capsaspora owczarzaki. However, MAGUKs are absent from fungi, amoebozoans or any other eukaryote. The repertoire of MAGUKs in Placozoa and eumetazoan taxa (Cnidaria + Bilateria is quite similar, except for one class that is missing in Trichoplax, while Porifera have a simpler MAGUK repertoire. However, Vertebrata have undergone several independent duplications and exhibit two exclusive MAGUK classes. Three different MAGUK types are found in both M. brevicollis and C. owczarzaki: DLG, MPP and MAGI. Furthermore, M. brevicollis has suffered a lineage-specific diversification. Conclusions The diversification of the MAGUK protein gene family occurred, most probably, prior to the divergence between Metazoa+choanoflagellates and the Capsaspora+Ministeria clade. A MAGI-like, a DLG-like, and a MPP-like ancestral genes were already present in the unicellular ancestor of Metazoa, and new gene members have been incorporated through metazoan evolution within two major periods, one before the sponge-eumetazoan split and another within the vertebrate lineage. Moreover, choanoflagellates have suffered an independent MAGUK

  15. Challenges in biotechnology at LLNL: from genes to proteins

    Energy Technology Data Exchange (ETDEWEB)

    Albala, J S

    1999-03-11

    This effort has undertaken the task of developing a link between the genomics, DNA repair and structural biology efforts within the Biology and Biotechnology Research Program at LLNL. Through the advent of the I.M.A.G.E. (Integrated Molecular Analysis of Genomes and their Expression) Consortium, a world-wide effort to catalog the largest public collection of genes, accepted and maintained within BBRP, it is now possible to systematically express the protein complement of these to further elucidate novel gene function and structure. The work has ensued in four phases, outlined as follows: (1) Gene and System selection; (2) Protein expression and purification; (3) Structural analysis; and (4) biological integration. Proteins to be expressed have been those of high programmatic interest. This includes, in particular, proteins involved in the maintenance of genome integrity, particularly those involved in the repair of DNA damage, including ERCC1, ERCC4, XRCC2, XRCC3, XRCC9, HEX1, APN1, p53, RAD51B, RAD51C, and RAD51. Full-length cDNA cognates of selected genes were isolated, and cloned into baculovirus-based expression vectors. The baculoviral expression system for protein over-expression is now well-established in the Albala laboratory. Procedures have been successfully optimized for full-length cDNA clining into expression vectors for protein expression from recombinant constructs. This includes the reagents, cell lines, techniques necessary for expression of recombinant baculoviral constructs in Spodoptera frugiperda (Sf9) cells. The laboratory has also generated a high-throughput baculoviral expression paradigm for large scale expression and purification of human recombinant proteins amenable to automation.

  16. Gene ontology based transfer learning for protein subcellular localization

    Directory of Open Access Journals (Sweden)

    Zhou Shuigeng

    2011-02-01

    Full Text Available Abstract Background Prediction of protein subcellular localization generally involves many complex factors, and using only one or two aspects of data information may not tell the true story. For this reason, some recent predictive models are deliberately designed to integrate multiple heterogeneous data sources for exploiting multi-aspect protein feature information. Gene ontology, hereinafter referred to as GO, uses a controlled vocabulary to depict biological molecules or gene products in terms of biological process, molecular function and cellular component. With the rapid expansion of annotated protein sequences, gene ontology has become a general protein feature that can be used to construct predictive models in computational biology. Existing models generally either concatenated the GO terms into a flat binary vector or applied majority-vote based ensemble learning for protein subcellular localization, both of which can not estimate the individual discriminative abilities of the three aspects of gene ontology. Results In this paper, we propose a Gene Ontology Based Transfer Learning Model (GO-TLM for large-scale protein subcellular localization. The model transfers the signature-based homologous GO terms to the target proteins, and further constructs a reliable learning system to reduce the adverse affect of the potential false GO terms that are resulted from evolutionary divergence. We derive three GO kernels from the three aspects of gene ontology to measure the GO similarity of two proteins, and derive two other spectrum kernels to measure the similarity of two protein sequences. We use simple non-parametric cross validation to explicitly weigh the discriminative abilities of the five kernels, such that the time & space computational complexities are greatly reduced when compared to the complicated semi-definite programming and semi-indefinite linear programming. The five kernels are then linearly merged into one single kernel for

  17. rec genes and homologous recombination proteins in Escherichia coli.

    Science.gov (United States)

    Clark, A J

    1991-04-01

    The twenty-five years since the first published report of recA mutants in Escherichia coli has seen the identification of more than 12 other recombination genes. The genes are usually grouped into three pathways named RecBCD, RecE and RecF for prominent genes which function in each. A proposal is made here that there are two RecF pathways, one sensitive and one resistant to exonuclease I, the SbcB enzyme. Five methods of grouping the genes functionally are discussed: 1) by enzyme activity, 2) by common indirect suppressor, 3) by common phenotype, 4) by common regulation and 5) by epistasis. Five classes of enzyme activities implicated in recombination are discussed according to their involvement in presynapsis, synapsis or postsynapsis: 1) nucleases 2) helicases 3) DNA-binding proteins 4) topoisomerases and 5) ligases. Plausible presynaptic steps for the RecBCD, RecF (SbcBS) and RecE pathways show the common feature of generating 3'-terminated single-stranded DNA (ssDNA). On this ssDNA it is proposed that a RecA protein filament is generated discontinuously. This implies the existence of nucleation and possibly measurement and 3' end protection proteins. Specific proposals are made for which recombination genes might encode such products. Finally the generality of the RecA-ssDNA-filament mechanism of synapsis in the cellular biological world is discussed.

  18. Gene, protein, and network of male sterility in rice.

    Science.gov (United States)

    Wang, Kun; Peng, Xiaojue; Ji, Yanxiao; Yang, Pingfang; Zhu, Yingguo; Li, Shaoqing

    2013-01-01

    Rice is one of the most important model crop plants whose heterosis has been well-exploited in commercial hybrid seed production via a variety of types of male-sterile lines. Hybrid rice cultivation area is steadily expanding around the world, especially in Southern Asia. Characterization of genes and proteins related to male sterility aims to understand how and why the male sterility occurs, and which proteins are the key players for microspores abortion. Recently, a series of genes and proteins related to cytoplasmic male sterility (CMS), photoperiod-sensitive male sterility, self-incompatibility, and other types of microspores deterioration have been characterized through genetics or proteomics. Especially the latter, offers us a powerful and high throughput approach to discern the novel proteins involving in male-sterile pathways which may help us to breed artificial male-sterile system. This represents an alternative tool to meet the critical challenge of further development of hybrid rice. In this paper, we reviewed the recent developments in our understanding of male sterility in rice hybrid production across gene, protein, and integrated network levels, and also, present a perspective on the engineering of male-sterile lines for hybrid rice production.

  19. Gene, protein and network of male sterility in rice

    Directory of Open Access Journals (Sweden)

    Wang eKun

    2013-04-01

    Full Text Available Rice is one of the most important model crop plants whose heterosis has been well exploited in commercial hybrid seed production via a variety of types of male sterile lines. Hybrid rice cultivation area is steadily expanding around the world, especially in Southern Asia. Characterization of genes and proteins related to male sterility aims to understand how and why the male sterility occurs, and which proteins are the key players for microspores abortion. Recently, a series of genes and proteins related to cytoplasmic male sterility, photoperiod sensitive male sterility, self-incompatibility and other types of microspores deterioration have been characterized through genetics or proteomics. Especially the latter, offers us a powerful and high throughput approach to discern the novel proteins involving in male-sterile pathways which may help us to breed artificial male-sterile system. This represents an alternative tool to meet the critical challenge of further development of hybrid rice. In this paper, we reviewed the recent developments in our understanding of male sterility in rice hybrid production across gene, protein and integrated network levels, and also, present a perspective on the engineering of male sterile lines for hybrid rice production.

  20. Role of Fatty Acid Binding Protein 5 (FABP5) in Breast Cancer Progression and Metastasis

    Science.gov (United States)

    2013-04-01

    Acids 41(4):789–796. doi: 10.1007/s00726-010-0666-4 7. Tripathi SC, Matta A, Kaur J, Grigull J, Chauhan SS, Thakar A, Shukla NK, Duggal R, DattaGupta...Chatterjee A, Sarkar M, Bhattacharya S, Chatterjee U, Ghosh MK (2012) Mechanism of beta-catenin- mediated transcriptional regulation of epidermal

  1. Recent Advances in Nucleic Acid Binding Aspects of Berberine Analogs and Implications for Drug Design.

    Science.gov (United States)

    Bhowmik, Debipreeta; Kumar, Gopinatha Suresh

    2016-01-01

    Berberine is one of the most widely known alkaloids belonging to the protoberberine group exhibiting myriad therapeutic properties. The anticancer potency of berberine appears to derive from its multiple actions including strong interaction with nucleic acids exhibiting adenine-thymine base pair specificity, inhibition of the enzymes topoisomerases and telomerases, and stabilizing the quadruplex structures. It was realized that the development of berberine as a potential anticancer agent necessitates enhancing its nucleic acid binding efficacy through appropriate structural modifications. More recently a number of such approaches have been attempted in various laboratories with great success. Several derivatives have been synthesized mostly with substitutions at the 8, 9 and 13 positions of the isoquinoline chromophore, and studied for enhanced nucleic acid binding activity. In this article, we present an up to date review of the details of the interaction of berberine and several of its important synthetic 8, 9 and 13 substituted derivatives with various nucleic acid structures reported recently. These studies provide interesting knowledge on the mode, mechanism, sequence and structural specificity of the binding of berberine derivatives and correlate structural and energetic aspects of the interaction providing better understanding of the structure- activity relations for designing and development of berberine based therapeutic agents with higher efficacy and therapeutic potential.

  2. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes.

    Science.gov (United States)

    Johnson, D G; Carayannopoulos, L; Capra, J D; Tucker, P W; Hanke, J H

    1990-03-01

    All immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression.

  3. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.G.; Carayannopoulos, L.; Capra, J.D.; Tucker, P.W. (Dept. of Microbiology, Southwestern Medical Center at Dallas, Dallas, TX (US)); Hanke, J.H. (Central Research, Dept. of Molecular Genetics, Pfizer, Inc., Groton, CT (US))

    1990-03-01

    All immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. The authors have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression.

  4. Mapping of the Mouse Actin Capping Protein Beta Subunit Gene

    Directory of Open Access Journals (Sweden)

    Cooper John A

    2000-07-01

    Full Text Available Abstract Background Capping protein (CP, a heterodimer of α and β subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filaments in vitro and controls actin assembly and cell motility in vivo. Vertebrates have three isoforms of CPβ produced by alternatively splicing from one gene; lower organisms have one gene and one isoform. Results We isolated genomic clones corresponding to the β subunit of mouse CP and identified its chromosomal location by interspecies backcross mapping. Conclusions The CPβ gene (Cappb1 mapped to Chromosome 4 between Cdc42 and D4Mit312. Three mouse mutations, snubnose, curly tail, and cribriform degeneration, map in the vicinity of the β gene.

  5. Effect of SNPs in protein kinase Czgene on gene expression in the reporter gene detection system

    Institute of Scientific and Technical Information of China (English)

    Zhuo Liu; Hong-Xia Sun; Yong-Wei Zhang; Yun-Feng Li; Jin Zuo; Yan Meng; Fu-De Fang

    2004-01-01

    AIM: To investigated the effects of the SNPs (rs411021,rs436045, rs427811, rs385039 and rs809912) on gene expression and further identify the susceptibility genes of type 2 diabetes.METHODS: Ten allele fragments (49 bp each) were synthesized according to the 5 SNPs mentioned above.These fragments were cloned into luciferase reporter gene vector and then transfected into HepG2 cells. The activity of the luciferase was assayed. Effects of the SNPs on RNA splicing were analyzed by bioinformatics.RESULTS: rs427811T allele and rs809912G allele enhanced the activity of the reporter gene expression. None of the 5 SNPs affected RNA splicing.CONCLUSION: SNPs in protein kinase Cz (PKCZ) gene probably play a role in the susceptibility to type 2 diabetes by affecting the expression level of the relevant genes.

  6. Automatic annotation of protein motif function with Gene Ontology terms

    Directory of Open Access Journals (Sweden)

    Gopalakrishnan Vanathi

    2004-09-01

    Full Text Available Abstract Background Conserved protein sequence motifs are short stretches of amino acid sequence patterns that potentially encode the function of proteins. Several sequence pattern searching algorithms and programs exist foridentifying candidate protein motifs at the whole genome level. However, amuch needed and importanttask is to determine the functions of the newly identified protein motifs. The Gene Ontology (GO project is an endeavor to annotate the function of genes or protein sequences with terms from a dynamic, controlled vocabulary and these annotations serve well as a knowledge base. Results This paperpresents methods to mine the GO knowledge base and use the association between the GO terms assigned to a sequence and the motifs matched by the same sequence as evidence for predicting the functions of novel protein motifs automatically. The task of assigning GO terms to protein motifsis viewed as both a binary classification and information retrieval problem, where PROSITE motifs are used as samples for mode training and functional prediction. The mutual information of a motif and aGO term association isfound to be a very useful feature. We take advantageof the known motifs to train a logistic regression classifier, which allows us to combine mutual information with other frequency-based features and obtain a probability of correctassociation. The trained logistic regression model has intuitively meaningful and logically plausible parameter values, and performs very well empirically according to our evaluation criteria. Conclusions In this research, different methods for automatic annotation of protein motifs have been investigated. Empirical result demonstrated that the methods have a great potential for detecting and augmenting information about thefunctions of newly discovered candidate protein motifs.

  7. KEGG as a reference resource for gene and protein annotation.

    Science.gov (United States)

    Kanehisa, Minoru; Sato, Yoko; Kawashima, Masayuki; Furumichi, Miho; Tanabe, Mao

    2016-01-04

    KEGG (http://www.kegg.jp/ or http://www.genome.jp/kegg/) is an integrated database resource for biological interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 complete genomes are annotated with KOs in the KEGG GENES database, which can be used as a reference data set for KO assignment and subsequent reconstruction of KEGG pathways and other molecular networks. As an annotation resource, the following improvements have been made. First, each KO record is re-examined and associated with protein sequence data used in experiments of functional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for antimicrobial resistance and drug interaction networks.

  8. A new essential protein discovery method based on the integration of protein-protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Li Min

    2012-03-01

    Full Text Available Abstract Background Identification of essential proteins is always a challenging task since it requires experimental approaches that are time-consuming and laborious. With the advances in high throughput technologies, a large number of protein-protein interactions are available, which have produced unprecedented opportunities for detecting proteins' essentialities from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. However, the network topology-based centrality measures are very sensitive to the robustness of network. Therefore, a new robust essential protein discovery method would be of great value. Results In this paper, we propose a new centrality measure, named PeC, based on the integration of protein-protein interaction and gene expression data. The performance of PeC is validated based on the protein-protein interaction network of Saccharomyces cerevisiae. The experimental results show that the predicted precision of PeC clearly exceeds that of the other fifteen previously proposed centrality measures: Degree Centrality (DC, Betweenness Centrality (BC, Closeness Centrality (CC, Subgraph Centrality (SC, Eigenvector Centrality (EC, Information Centrality (IC, Bottle Neck (BN, Density of Maximum Neighborhood Component (DMNC, Local Average Connectivity-based method (LAC, Sum of ECC (SoECC, Range-Limited Centrality (RL, L-index (LI, Leader Rank (LR, Normalized α-Centrality (NC, and Moduland-Centrality (MC. Especially, the improvement of PeC over the classic centrality measures (BC, CC, SC, EC, and BN is more than 50% when predicting no more than 500 proteins. Conclusions We demonstrate that the integration of protein-protein interaction network and gene expression data can help improve the precision of predicting essential proteins. The new centrality measure, PeC, is an effective essential protein discovery method.

  9. Crystallization and preliminary X-ray diffraction analysis of the sialic acid-binding domain (VP8*) of porcine rotavirus strain CRW-8

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Stacy A. [Institute for Glycomics, Griffith University (Gold Coast Campus) PMB 50, Gold Coast Mail Centre, Queensland 9726 (Australia); Holloway, Gavan; Coulson, Barbara S. [Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010 (Australia); Szyczew, Alex J.; Kiefel, Milton J.; Itzstein, Mark von; Blanchard, Helen, E-mail: h.blanchard@griffith.edu.au [Institute for Glycomics, Griffith University (Gold Coast Campus) PMB 50, Gold Coast Mail Centre, Queensland 9726 (Australia)

    2005-06-01

    The sialic acid-binding domain (VP8*) component of the porcine CRW-8 rotavirus spike protein has been overexpressed in E. coli, purified and co-crystallized with an N-acetylneuraminic acid derivative. X-ray diffraction data have been collected to 2.3 Å, which has enabled determination of the structure by molecular replacement. Rotavirus recognition and attachment to host cells involves interaction with the spike protein VP4 that projects outwards from the surface of the virus particle. An integral component of these spikes is the VP8* domain, which is implicated in the direct recognition and binding of sialic acid-containing cell-surface carbohydrates and facilitates subsequent invasion by the virus. The expression, purification, crystallization and preliminary X-ray diffraction analysis of VP8* from porcine CRW-8 rotavirus is reported. Diffraction data have been collected to 2.3 Å resolution, enabling the determination of the VP8* structure by molecular replacement.

  10. Analysis of ribosomal protein gene structures: implications for intron evolution.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Many spliceosomal introns exist in the eukaryotic nuclear genome. Despite much research, the evolution of spliceosomal introns remains poorly understood. In this paper, we tried to gain insights into intron evolution from a novel perspective by comparing the gene structures of cytoplasmic ribosomal proteins (CRPs and mitochondrial ribosomal proteins (MRPs, which are held to be of archaeal and bacterial origin, respectively. We analyzed 25 homologous pairs of CRP and MRP genes that together had a total of 527 intron positions. We found that all 12 of the intron positions shared by CRP and MRP genes resulted from parallel intron gains and none could be considered to be "conserved," i.e., descendants of the same ancestor. This was supported further by the high frequency of proto-splice sites at these shared positions; proto-splice sites are proposed to be sites for intron insertion. Although we could not definitively disprove that spliceosomal introns were already present in the last universal common ancestor, our results lend more support to the idea that introns were gained late. At least, our results show that MRP genes were intronless at the time of endosymbiosis. The parallel intron gains between CRP and MRP genes accounted for 2.3% of total intron positions, which should provide a reliable estimate for future inferences of intron evolution.

  11. Controlling for gene expression changes in transcription factor protein networks.

    Science.gov (United States)

    Banks, Charles A S; Lee, Zachary T; Boanca, Gina; Lakshminarasimhan, Mahadevan; Groppe, Brad D; Wen, Zhihui; Hattem, Gaye L; Seidel, Chris W; Florens, Laurence; Washburn, Michael P

    2014-06-01

    The development of affinity purification technologies combined with mass spectrometric analysis of purified protein mixtures has been used both to identify new protein-protein interactions and to define the subunit composition of protein complexes. Transcription factor protein interactions, however, have not been systematically analyzed using these approaches. Here, we investigated whether ectopic expression of an affinity tagged transcription factor as bait in affinity purification mass spectrometry experiments perturbs gene expression in cells, resulting in the false positive identification of bait-associated proteins when typical experimental controls are used. Using quantitative proteomics and RNA sequencing, we determined that the increase in the abundance of a set of proteins caused by overexpression of the transcription factor RelA is not sufficient for these proteins to then co-purify non-specifically and be misidentified as bait-associated proteins. Therefore, typical controls should be sufficient, and a number of different baits can be compared with a common set of controls. This is of practical interest when identifying bait interactors from a large number of different baits. As expected, we found several known RelA interactors enriched in our RelA purifications (NFκB1, NFκB2, Rel, RelB, IκBα, IκBβ, and IκBε). We also found several proteins not previously described in association with RelA, including the small mitochondrial chaperone Tim13. Using a variety of biochemical approaches, we further investigated the nature of the association between Tim13 and NFκB family transcription factors. This work therefore provides a conceptual and experimental framework for analyzing transcription factor protein interactions.

  12. Inference of gene-phenotype associations via protein-protein interaction and orthology.

    Directory of Open Access Journals (Sweden)

    Panwen Wang

    Full Text Available One of the fundamental goals of genetics is to understand gene functions and their associated phenotypes. To achieve this goal, in this study we developed a computational algorithm that uses orthology and protein-protein interaction information to infer gene-phenotype associations for multiple species. Furthermore, we developed a web server that provides genome-wide phenotype inference for six species: fly, human, mouse, worm, yeast, and zebrafish. We evaluated our inference method by comparing the inferred results with known gene-phenotype associations. The high Area Under the Curve values suggest a significant performance of our method. By applying our method to two human representative diseases, Type 2 Diabetes and Breast Cancer, we demonstrated that our method is able to identify related Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The web server can be used to infer functions and putative phenotypes of a gene along with the candidate genes of a phenotype, and thus aids in disease candidate gene discovery. Our web server is available at http://jjwanglab.org/PhenoPPIOrth.

  13. An improved method for scoring protein-protein interactions using semantic similarity within the gene ontology

    Directory of Open Access Journals (Sweden)

    Jain Shobhit

    2010-11-01

    Full Text Available Abstract Background Semantic similarity measures are useful to assess the physiological relevance of protein-protein interactions (PPIs. They quantify similarity between proteins based on their function using annotation systems like the Gene Ontology (GO. Proteins that interact in the cell are likely to be in similar locations or involved in similar biological processes compared to proteins that do not interact. Thus the more semantically similar the gene function annotations are among the interacting proteins, more likely the interaction is physiologically relevant. However, most semantic similarity measures used for PPI confidence assessment do not consider the unequal depth of term hierarchies in different classes of cellular location, molecular function, and biological process ontologies of GO and thus may over-or under-estimate similarity. Results We describe an improved algorithm, Topological Clustering Semantic Similarity (TCSS, to compute semantic similarity between GO terms annotated to proteins in interaction datasets. Our algorithm, considers unequal depth of biological knowledge representation in different branches of the GO graph. The central idea is to divide the GO graph into sub-graphs and score PPIs higher if participating proteins belong to the same sub-graph as compared to if they belong to different sub-graphs. Conclusions The TCSS algorithm performs better than other semantic similarity measurement techniques that we evaluated in terms of their performance on distinguishing true from false protein interactions, and correlation with gene expression and protein families. We show an average improvement of 4.6 times the F1 score over Resnik, the next best method, on our Saccharomyces cerevisiae PPI dataset and 2 times on our Homo sapiens PPI dataset using cellular component, biological process and molecular function GO annotations.

  14. PPISEARCHENGINE: gene ontology-based search for protein-protein interactions.

    Science.gov (United States)

    Park, Byungkyu; Cui, Guangyu; Lee, Hyunjin; Huang, De-Shuang; Han, Kyungsook

    2013-01-01

    This paper presents a new search engine called PPISearchEngine which finds protein-protein interactions (PPIs) using the gene ontology (GO) and the biological relations of proteins. For efficient retrieval of PPIs, each GO term is assigned a prime number and the relation between the terms is represented by the product of prime numbers. This representation is hidden from users but facilitates the search for the interactions of a query protein by unique prime factorisation of the number that represents the query protein. For a query protein, PPISearchEngine considers not only the GO term associated with the query protein but also the GO terms at the lower level than the GO term in the GO hierarchy, and finds all the interactions of the query protein which satisfy the search condition. In contrast, the standard keyword-matching or ID-matching search method cannot find the interactions of a protein unless the interactions involve a protein with explicit annotations. To the best of our knowledge, this search engine is the first method that can process queries like 'for protein p with GO [Formula: see text], find p's interaction partners with GO [Formula: see text]'. PPISearchEngine is freely available to academics at http://search.hpid.org/.

  15. Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia

    Institute of Scientific and Technical Information of China (English)

    Yu Gao; Lumei Chi; Yinshi Jin; Guangxian Nan

    2012-01-01

    PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.

  16. Loss of Bloom syndrome protein destabilizes human gene cluster architecture.

    Science.gov (United States)

    Killen, Michael W; Stults, Dawn M; Adachi, Noritaka; Hanakahi, Les; Pierce, Andrew J

    2009-09-15

    Bloom syndrome confers strong predisposition to malignancy in multiple tissue types. The Bloom syndrome patient (BLM) protein defective in the disease biochemically functions as a Holliday junction dissolvase and human cells lacking functional BLM show 10-fold elevated rates of sister chromatid exchange. Collectively, these phenomena suggest that dysregulated mitotic recombination drives the genomic instability underpinning the development of cancer in these individuals. Here we use physical analysis of the highly repeated, highly self-similar human ribosomal RNA gene clusters as sentinel biomarkers for dysregulated homologous recombination to demonstrate that loss of BLM protein function causes a striking increase in spontaneous molecular level genomic restructuring. Analysis of single-cell derived sub-clonal populations from wild-type human cell lines shows that gene cluster architecture is ordinarily very faithfully preserved under mitosis, but is so unstable in cell lines derived from BLMs as to make gene cluster architecture in different sub-clonal populations essentially unrecognizable one from another. Human cells defective in a different RecQ helicase, the WRN protein involved in the premature aging Werner syndrome, do not exhibit the gene cluster instability (GCI) phenotype, indicating that the BLM protein specifically, rather than RecQ helicases generally, holds back this recombination-mediated genomic instability. An ataxia-telangiectasia defective cell line also shows elevated rDNA GCI, although not to the extent of BLM defective cells. Genomic restructuring mediated by dysregulated recombination between the abundant low-copy repeats in the human genome may prove to be an important additional mechanism of genomic instability driving the initiation and progression of human cancer.

  17. Transcriptional Modulation of Heat-Shock Protein Gene Expression

    OpenAIRE

    Anastasis Stephanou; Latchman, David S.

    2011-01-01

    Heat-shock proteins (Hsps) are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex sig...

  18. Transcriptional modulation of heat-shock protein gene expression.

    OpenAIRE

    A. Stephanou; Latchman, D S

    2011-01-01

    Heat-shock proteins (Hsps) are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex sig...

  19. Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases.

    Science.gov (United States)

    Tuller, T; Atar, S; Ruppin, E; Gurevich, M; Achiron, A

    2013-03-01

    The aim of this study is to understand intracellular regulatory mechanisms in peripheral blood mononuclear cells (PBMCs), which are either common to many autoimmune diseases or specific to some of them. We incorporated large-scale data such as protein-protein interactions, gene expression and demographical information of hundreds of patients and healthy subjects, related to six autoimmune diseases with available large-scale gene expression measurements: multiple sclerosis (MS), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), Crohn's disease (CD), ulcerative colitis (UC) and type 1 diabetes (T1D). These data were analyzed concurrently by statistical and systems biology approaches tailored for this purpose. We found that chemokines such as CXCL1-3, 5, 6 and the interleukin (IL) IL8 tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In addition, the anti-apoptotic gene BCL3, interferon-γ (IFNG), and the vitamin D receptor (VDR) gene physically interact with significantly many genes that tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In general, similar cellular processes tend to be differentially expressed in PBMC in the analyzed autoimmune diseases. Specifically, the cellular processes related to cell proliferation (for example, epidermal growth factor, platelet-derived growth factor, nuclear factor-κB, Wnt/β-catenin signaling, stress-activated protein kinase c-Jun NH2-terminal kinase), inflammatory response (for example, interleukins IL2 and IL6, the cytokine granulocyte-macrophage colony-stimulating factor and the B-cell receptor), general signaling cascades (for example, mitogen-activated protein kinase, extracellular signal-regulated kinase, p38 and TRK) and apoptosis are activated in most of the analyzed autoimmune diseases. However, our results suggest that in each of the analyzed diseases, apoptosis and chemotaxis are activated via

  20. Prolactin receptor and signal transduction to milk protein genes

    Energy Technology Data Exchange (ETDEWEB)

    Djiane, J.; Daniel, N.; Bignon, C. [Unite d`Endocrinologie Moleculaire, Jouy en Josas (France)] [and others

    1994-06-01

    After cloning of the mammary gland prolactin (PRL) receptor cDNA, a functional assay was established using co-transfection of PRL receptor cDNA together with a milk protein promoter/chloramphenicol acetyl transferase (CAT) construct in Chinese hamster ovary (CHO) cells. Different mutants of the PRL receptor were tested in this CAT assay to delimit the domains in the receptor necessary for signal transduction to milk protein genes. In CHO cells stably transfected with PRL receptor cDNA, high numbers of PRL receptor are expressed. By metabolic labeling and immunoprecipitation, expressed PRL receptor was identified as a single species of 100 kDa. Using these cells, we analyzed the effects of PRL on intracellular free Ca{sup ++} concentration. PRL stimulates Ca{sup ++} entry and induces secondary Ca{sup ++} mobilization. The entry of Ca{sup ++} is a result of an increase in K{sup +} conductance that hyperpolarizes the membranes. We have also analyzed tyrosine phosphorylation induced by PRL. In CHO cells stably transfected with PRL receptor cDNA, PRL induced a very rapid and transient tyrosine phosphorylation of a 100-kDa protein which is most probably the PRL receptor. The same finding was obtained in mammary membranes after PRL injection to lactating rabbits. Whereas tyrosine kinase inhibitors genistein and lavendustin were without effect, PRL stimulation of milk protein gene promoters was partially inhibited by 2 {mu}M herbimycin in CHO cells co-transfected with PRL receptor cDNA and the {Beta} lactoglobulin CAT construct. Taken together these observations indicate that the cytoplasmic domain of the PRL receptor interacts with one or several tyrosine kinases, which may represent early postreceptor events necessary for PRL signal transduction to milk protein genes. 14 refs., 4 figs.

  1. Protein-protein interaction inference based on semantic similarity of Gene Ontology terms.

    Science.gov (United States)

    Zhang, Shu-Bo; Tang, Qiang-Rong

    2016-07-21

    Identifying protein-protein interactions is important in molecular biology. Experimental methods to this issue have their limitations, and computational approaches have attracted more and more attentions from the biological community. The semantic similarity derived from the Gene Ontology (GO) annotation has been regarded as one of the most powerful indicators for protein interaction. However, conventional methods based on GO similarity fail to take advantage of the specificity of GO terms in the ontology graph. We proposed a GO-based method to predict protein-protein interaction by integrating different kinds of similarity measures derived from the intrinsic structure of GO graph. We extended five existing methods to derive the semantic similarity measures from the descending part of two GO terms in the GO graph, then adopted a feature integration strategy to combines both the ascending and the descending similarity scores derived from the three sub-ontologies to construct various kinds of features to characterize each protein pair. Support vector machines (SVM) were employed as discriminate classifiers, and five-fold cross validation experiments were conducted on both human and yeast protein-protein interaction datasets to evaluate the performance of different kinds of integrated features, the experimental results suggest the best performance of the feature that combines information from both the ascending and the descending parts of the three ontologies. Our method is appealing for effective prediction of protein-protein interaction.

  2. Amyloid diseases of yeast: prions are proteins acting as genes.

    Science.gov (United States)

    Wickner, Reed B; Edskes, Herman K; Bateman, David A; Kelly, Amy C; Gorkovskiy, Anton; Dayani, Yaron; Zhou, Albert

    2014-01-01

    The unusual genetic properties of the non-chromosomal genetic elements [URE3] and [PSI+] led to them being identified as prions (infectious proteins) of Ure2p and Sup35p respectively. Ure2p and Sup35p, and now several other proteins, can form amyloid, a linear ordered polymer of protein monomers, with a part of each molecule, the prion domain, forming the core of this β-sheet structure. Amyloid filaments passed to a new cell seed the conversion of the normal form of the protein into the same amyloid form. The cell's phenotype is affected, usually from the deficiency of the normal form of the protein. Solid-state NMR studies indicate that the yeast prion amyloids are in-register parallel β-sheet structures, in which each residue (e.g. Asn35) forms a row along the filament long axis. The favourable interactions possible for aligned identical hydrophilic and hydrophobic residues are believed to be the mechanism for propagation of amyloid conformation. Thus, just as DNA mediates inheritance by templating its own sequence, these proteins act as genes by templating their conformation. Distinct isolates of a given prion have different biological properties, presumably determined by differences between the amyloid structures. Many lines of evidence indicate that the Saccharomyces cerevisiae prions are pathological disease agents, although the example of the [Het-s] prion of Podospora anserina shows that a prion can have beneficial aspects.

  3. Genes encoding calmodulin-binding proteins in the Arabidopsis genome

    Science.gov (United States)

    Reddy, Vaka S.; Ali, Gul S.; Reddy, Anireddy S N.

    2002-01-01

    Analysis of the recently completed Arabidopsis genome sequence indicates that approximately 31% of the predicted genes could not be assigned to functional categories, as they do not show any sequence similarity with proteins of known function from other organisms. Calmodulin (CaM), a ubiquitous and multifunctional Ca(2+) sensor, interacts with a wide variety of cellular proteins and modulates their activity/function in regulating diverse cellular processes. However, the primary amino acid sequence of the CaM-binding domain in different CaM-binding proteins (CBPs) is not conserved. One way to identify most of the CBPs in the Arabidopsis genome is by protein-protein interaction-based screening of expression libraries with CaM. Here, using a mixture of radiolabeled CaM isoforms from Arabidopsis, we screened several expression libraries prepared from flower meristem, seedlings, or tissues treated with hormones, an elicitor, or a pathogen. Sequence analysis of 77 positive clones that interact with CaM in a Ca(2+)-dependent manner revealed 20 CBPs, including 14 previously unknown CBPs. In addition, by searching the Arabidopsis genome sequence with the newly identified and known plant or animal CBPs, we identified a total of 27 CBPs. Among these, 16 CBPs are represented by families with 2-20 members in each family. Gene expression analysis revealed that CBPs and CBP paralogs are expressed differentially. Our data suggest that Arabidopsis has a large number of CBPs including several plant-specific ones. Although CaM is highly conserved between plants and animals, only a few CBPs are common to both plants and animals. Analysis of Arabidopsis CBPs revealed the presence of a variety of interesting domains. Our analyses identified several hypothetical proteins in the Arabidopsis genome as CaM targets, suggesting their involvement in Ca(2+)-mediated signaling networks.

  4. Integrating gene synthesis and microfluidic protein analysis for rapid protein engineering.

    Science.gov (United States)

    Blackburn, Matthew C; Petrova, Ekaterina; Correia, Bruno E; Maerkl, Sebastian J

    2016-04-20

    The capability to rapidly design proteins with novel functions will have a significant impact on medicine, biotechnology and synthetic biology. Synthetic genes are becoming a commodity, but integrated approaches have yet to be developed that take full advantage of gene synthesis. We developed a solid-phase gene synthesis method based on asymmetric primer extension (APE) and coupled this process directly to high-throughput, on-chip protein expression, purification and characterization (via mechanically induced trapping of molecular interactions, MITOMI). By completely circumventing molecular cloning and cell-based steps, APE-MITOMI reduces the time between protein design and quantitative characterization to 3-4 days. With APE-MITOMI we synthesized and characterized over 400 zinc-finger (ZF) transcription factors (TF), showing that although ZF TFs can be readily engineered to recognize a particular DNA sequence, engineering the precise binding energy landscape remains challenging. We also found that it is possible to engineer ZF-DNA affinity precisely and independently of sequence specificity and that in silico modeling can explain some of the observed affinity differences. APE-MITOMI is a generic approach that should facilitate fundamental studies in protein biophysics, and protein design/engineering.

  5. Gene Delivery into Plant Cells for Recombinant Protein Production

    Directory of Open Access Journals (Sweden)

    Qiang Chen

    2015-01-01

    Full Text Available Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene delivery into plant cells for large-scale manufacturing of recombinant proteins. General gene delivery methodologies in plants are first summarized, followed by extensive discussion on the application and scalability of each agroinfiltration method. New development of a spray-based agroinfiltration and its application on field-grown plants is highlighted. The discussion of agroinfiltration vectors focuses on their applications for producing complex and heteromultimeric proteins and is updated with the development of bridge vectors. Progress on agroinfiltration in Nicotiana and non-Nicotiana plant hosts is subsequently showcased in context of their applications for producing high-value human biologics and low-cost and high-volume industrial enzymes. These new advancements in agroinfiltration greatly enhance the robustness and scalability of transgene delivery in plants, facilitating the adoption of plant transient expression systems for manufacturing recombinant proteins with a broad range of applications.

  6. Neurotoxocarosis alters myelin protein gene transcription and expression.

    Science.gov (United States)

    Heuer, Lea; Beyerbach, Martin; Lühder, Fred; Beineke, Andreas; Strube, Christina

    2015-06-01

    Neurotoxocarosis is an infection of the central nervous system caused by migrating larvae of the common dog and cat roundworms (Toxocara canis and Toxocara cati), which are zoonotic agents. As these parasites are prevalent worldwide and neuropathological and molecular investigations on neurotoxocarosis are scare, this study aims to characterise nerve fibre demyelination associated with neurotoxocarosis on a molecular level. Transcription of eight myelin-associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined in the mouse model during six time points of the chronic phase of infection using qRT-PCR. Expression of selected proteins was analysed by Western blotting or immunohistochemistry. Additionally, demyelination and neuronal damage were investigated histologically. Significant differences (p ≤ 0.05) between transcription rates of T. canis-infected and uninfected control mice were detected for all analysed genes while T. cati affected five of eight investigated genes. Interestingly, 2', 3 ´-cyclic nucleotide 3'-phosphodiesterase (Cnp) and myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and T. cati-infected mice preceding demyelination. Later, CNPase expression was additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated in cerebra and cerebella of T. canis-infected mice when severe demyelination was present 120 days post infectionem (dpi). The transcriptional pattern observed in the present study appears to reflect direct traumatic and hypoxic effects of larval migration as well as secondary processes including host immune reactions, demyelination and attempts to remyelinate damaged areas.

  7. Differential expression of G protein alpha and ß subunit genes during development of Phytophthora infestans

    NARCIS (Netherlands)

    Laxalt, A.M.; Latijnhouwers, M.; Hulten, van M.; Govers, F.

    2002-01-01

    A G protein subunit gene (pigpa1) and a G protein subunit gene (pigpb1) were isolated from the oomycete Phytophthora infestans, the causal agent of potato late blight. Heterotrimeric G proteins are evolutionary conserved GTP-binding proteins that are composed of ,, and subunits and participate in di

  8. Evolutionary Characteristics of Missing Proteins: Insights into the Evolution of Human Chromosomes Related to Missing-Protein-Encoding Genes.

    Science.gov (United States)

    Xu, Aishi; Li, Guang; Yang, Dong; Wu, Songfeng; Ouyang, Hongsheng; Xu, Ping; He, Fuchu

    2015-12-01

    Although the "missing protein" is a temporary concept in C-HPP, the biological information for their "missing" could be an important clue in evolutionary studies. Here we classified missing-protein-encoding genes into two groups, the genes encoding PE2 proteins (with transcript evidence) and the genes encoding PE3/4 proteins (with no transcript evidence). These missing-protein-encoding genes distribute unevenly among different chromosomes, chromosomal regions, or gene clusters. In the view of evolutionary features, PE3/4 genes tend to be young, spreading at the nonhomology chromosomal regions and evolving at higher rates. Interestingly, there is a higher proportion of singletons in PE3/4 genes than the proportion of singletons in all genes (background) and OTCSGs (organ, tissue, cell type-specific genes). More importantly, most of the paralogous PE3/4 genes belong to the newly duplicated members of the paralogous gene groups, which mainly contribute to special biological functions, such as "smell perception". These functions are heavily restricted into specific type of cells, tissues, or specific developmental stages, acting as the new functional requirements that facilitated the emergence of the missing-protein-encoding genes during evolution. In addition, the criteria for the extremely special physical-chemical proteins were first set up based on the properties of PE2 proteins, and the evolutionary characteristics of those proteins were explored. Overall, the evolutionary analyses of missing-protein-encoding genes are expected to be highly instructive for proteomics and functional studies in the future.

  9. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower

    Science.gov (United States)

    The relative healthful potential of cooked beets, okra, eggplant, asparagus, carrots, green beans, cauliflower and turnips was evaluated by determining their in vitro bile acid binding using a mixture of bile acids secreted in human bile at a duodenal physiological pH of 6.3. Six treatments and two...

  10. A rhodopsin-like protein in Cyanophora paradoxa: gene sequence and protein immunolocalization.

    Science.gov (United States)

    Frassanito, Anna Maria; Barsanti, Laura; Passarelli, Vincenzo; Evangelista, Valtere; Gualtieri, Paolo

    2010-03-01

    Here, we report the DNA sequence of the rhodopsin gene in the alga Cyanophora paradoxa (Glaucophyta). The primers were designed according to the conserved regions of prokaryotic and eukaryotic rhodopsin-like proteins deposited in the GenBank. The sequence consists of 1,272 bp comprised of 5 introns. The correspondent protein, named Cyanophopsin, showed high identity to rhodopsin-like proteins of Archea, Bacteria, Fungi, and Algae. At the N-terminal, the protein is characterized by a region with no transmembrane alpha-helices (80 aa), followed by a region with 7alpha-helices (219 aa) and a shorter 35-aa C-terminal region. The DNA sequence of the N-terminal region was expressed in E. coli and the recombinant purified peptide was used as antigen in hens to obtain polyclonal antibodies. Indirect immunofluorescence in C. paradoxa cells showed a marked labeling of the muroplast (aka cyanelle) membrane.

  11. Expression of green fluoscrescent protein gene in Sclerotinia sclerotiorum

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun-zheng; YANG Qian; YANG Lei

    2009-01-01

    Protoplasts of the pathogenic plant fungus,Sclerotinia sclerotiorum,were transformed using the pPGF plasmid,which contains green fluorescent protein gene,under the control of Aspergillus nidulans regula-tory sequences,The pPGF plasmid was introduced by PEG/CaCl2 treatment.Positive transformants were har-Vested with hygromycin B(HYG) resistance as selective marker,and then were observed with green fluores-cence phenomena in response to blue light,which suggested that GFP gene was cloned into genome DNA of s.sclerotiorum.The transformants were verified mitotically stable by Southern blotting analysis and passage cultu-ring.This study is deVeloped as an initial step for further research into infection mechanisms of S.sclerotiorum to Plants and ineraetions with bio-control fungus.

  12. Alpha-synuclein gene structure,evolution,and protein aggregation

    Institute of Scientific and Technical Information of China (English)

    Lili Xiong; Peng Zhao; Zhiyun Guo; Jianhua Zhang; Diqiang Li; Canquan Mao

    2010-01-01

    α-synuclein,a member of the synuclein family,is predominately expressed in brain tissues,where it is the major component of Lewy bodies,the major hallmark of Parkinson's disease.We analyzed the phylogenetics,gene structure,and effects of different forms of α-synuclein on in vitro protein aggregation.The synuclein phylogenetic tree showed that sequences could be classified into α,β,and γ protein groups.The orthologous gene α-,β-and γ-synuclein showed similar evolutionary distance to the paralogous gene α-,β-and γ-synuclein.Bioinformatics analysis suggests that the amino-acid sequence of human α-synuclein can be divided into three regions: N-terminal amphipathic region(1-60),central hydrophobic non-amyloid beta component segment(61-95),and the C-terminal acidic part(96-140).The mutant site of A30P is at the second exon of α-synuclein,whereas E46K is located at the third exon of α-synuclein.α-synuclein alternative splicing results in four isomers,and five exons,all of which participate in protein coding,comprising 140 amino acids to produce the major α-synuclein in vivo.The threeα-synuclein isoforms are products of alternative splicing,α-synuclein 126,112 and 98.We also review the genetic and cellular factors that affect the aggregation of α-synuclein and compounds that inhibit aggregation.A better understanding of α-synuclein sequences,structure,and function may allow better targeted therapy and diagnosis of α-synuclein in Parkinson's disease and other neurodegenerative diseases.

  13. In vitro RNase and nucleic acid binding activities implicate coilin in U snRNA processing.

    Directory of Open Access Journals (Sweden)

    Hanna J Broome

    Full Text Available Coilin is known as the marker protein for Cajal bodies (CBs, subnuclear domains important for the biogenesis of small nuclear ribonucleoproteins (snRNPs which function in pre-mRNA splicing. CBs associate non-randomly with U1 and U2 gene loci, which produce the small nuclear RNA (snRNA component of the respective snRNP. Despite recognition as the CB marker protein, coilin is primarily nucleoplasmic, and the function of this fraction is not fully characterized. Here we show that coilin binds double stranded DNA and has RNase activity in vitro. U1 and U2 snRNAs undergo a processing event of the primary transcript prior to incorporation in the snRNP. We find that coilin displays RNase activity within the CU region of the U2 snRNA primary transcript in vitro, and that coilin knockdown results in accumulation of the 3' pre-processed U1 and U2 snRNA. These findings present new characteristics of coilin in vitro, and suggest additional functions of the protein in vivo.

  14. Transcriptional Modulation of Heat-Shock Protein Gene Expression

    Directory of Open Access Journals (Sweden)

    Anastasis Stephanou

    2011-01-01

    Full Text Available Heat-shock proteins (Hsps are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex signaling pathways regulating Hsp expression may lead to novel therapeutic targets.

  15. Transcriptional modulation of heat-shock protein gene expression.

    Science.gov (United States)

    Stephanou, Anastasis; Latchman, David S

    2011-01-01

    Heat-shock proteins (Hsps) are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex signaling pathways regulating Hsp expression may lead to novel therapeutic targets.

  16. Growing functional modules from a seed protein via integration of protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Dimitrakopoulou Konstantina

    2007-10-01

    Full Text Available Abstract Background Nowadays modern biology aims at unravelling the strands of complex biological structures such as the protein-protein interaction (PPI networks. A key concept in the organization of PPI networks is the existence of dense subnetworks (functional modules in them. In recent approaches clustering algorithms were applied at these networks and the resulting subnetworks were evaluated by estimating the coverage of well-established protein complexes they contained. However, most of these algorithms elaborate on an unweighted graph structure which in turn fails to elevate those interactions that would contribute to the construction of biologically more valid and coherent functional modules. Results In the current study, we present a method that corroborates the integration of protein interaction and microarray data via the discovery of biologically valid functional modules. Initially the gene expression information is overlaid as weights onto the PPI network and the enriched PPI graph allows us to exploit its topological aspects, while simultaneously highlights enhanced functional association in specific pairs of proteins. Then we present an algorithm that unveils the functional modules of the weighted graph by expanding a kernel protein set, which originates from a given 'seed' protein used as starting-point. Conclusion The integrated data and the concept of our approach provide reliable functional modules. We give proofs based on yeast data that our method manages to give accurate results in terms both of structural coherency, as well as functional consistency.

  17. Protein-protein interactions prediction based on iterative clique extension with gene ontology filtering.

    Science.gov (United States)

    Yang, Lei; Tang, Xianglong

    2014-01-01

    Cliques (maximal complete subnets) in protein-protein interaction (PPI) network are an important resource used to analyze protein complexes and functional modules. Clique-based methods of predicting PPI complement the data defection from biological experiments. However, clique-based predicting methods only depend on the topology of network. The false-positive and false-negative interactions in a network usually interfere with prediction. Therefore, we propose a method combining clique-based method of prediction and gene ontology (GO) annotations to overcome the shortcoming and improve the accuracy of predictions. According to different GO correcting rules, we generate two predicted interaction sets which guarantee the quality and quantity of predicted protein interactions. The proposed method is applied to the PPI network from the Database of Interacting Proteins (DIP) and most of the predicted interactions are verified by another biological database, BioGRID. The predicted protein interactions are appended to the original protein network, which leads to clique extension and shows the significance of biological meaning.

  18. Protein-Protein Interactions Prediction Based on Iterative Clique Extension with Gene Ontology Filtering

    Directory of Open Access Journals (Sweden)

    Lei Yang

    2014-01-01

    Full Text Available Cliques (maximal complete subnets in protein-protein interaction (PPI network are an important resource used to analyze protein complexes and functional modules. Clique-based methods of predicting PPI complement the data defection from biological experiments. However, clique-based predicting methods only depend on the topology of network. The false-positive and false-negative interactions in a network usually interfere with prediction. Therefore, we propose a method combining clique-based method of prediction and gene ontology (GO annotations to overcome the shortcoming and improve the accuracy of predictions. According to different GO correcting rules, we generate two predicted interaction sets which guarantee the quality and quantity of predicted protein interactions. The proposed method is applied to the PPI network from the Database of Interacting Proteins (DIP and most of the predicted interactions are verified by another biological database, BioGRID. The predicted protein interactions are appended to the original protein network, which leads to clique extension and shows the significance of biological meaning.

  19. Analysis of Protein–Protein Interactions in MCF-7 and MDA-MB-231 Cell Lines Using Phthalic Acid Chemical

    Directory of Open Access Journals (Sweden)

    Shih-Shin Liang

    2014-11-01

    Full Text Available Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein–protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, which were modified using the silanized linker 3-aminopropyl triethoxyslane (APTES. Incubation with cell lysates from breast cancer cell lines revealed interactions between phthalic acid and cellular proteins in MCF-7 and MDA-MB-231 cells. Subsequent proteomics analyses indicated 22 phthalic acid-binding proteins in both cell types, including heat shock cognate 71-kDa protein, ATP synthase subunit beta, and heat shock protein HSP 90-beta. In addition, 21 MCF-7-specific and 32 MDA-MB-231 specific phthalic acid-binding proteins were identified, including related proteasome proteins, heat shock 70-kDa protein, and NADPH dehydrogenase and ribosomal correlated proteins, ras-related proteins, and members of the heat shock protein family, respectively.

  20. [Expression of rice dwarf virus outer coat protein gene(S8) in insect cells].

    Science.gov (United States)

    Li, S; Liu, H; Chen, Z; Li, Y

    2001-04-01

    Outer coat protein gene(S8) of RDV was cloned into the transfer vector pVL 1393 to construct a recombinant vector pVL1393-S8. The recombinant vector pVL1393-S8 and the linear baculovirus RP23. LacZ were cotransfected into sf9 cells to produce the recombinant virus RP23-S8. RP23-S8 infected sf9 cells were collected and analysed by SDS-PAGE and Western-blot. The results showed that the S8 gene of RDV was expressed in sf9 cells and the expression level of sf9 cells was higher between 72-96 h after infected.

  1. The FU gene and its possible protein isoforms

    Directory of Open Access Journals (Sweden)

    Nöthen Markus M

    2004-07-01

    Full Text Available Abstract Background FU is the human homologue of the Drosophila gene fused whose product fused is a positive regulator of the transcription factor Cubitus interruptus (Ci. Thus, FU may act as a regulator of the human counterparts of Ci, the GLI transcription factors. Since Ci and GLI are targets of Hedgehog signaling in development and morphogenesis, it is expected that FU plays an important role in Sonic, Desert and/or Indian Hedgehog induced cellular signaling. Results The FU gene was identified on chromosome 2q35 at 217.56 Mb and its exon-intron organization determined. The human developmental disorder Syndactyly type 1 (SD1 maps to this region on chromosome 2 and the FU coding region was sequenced using genomic DNA from an affected individual in a linked family. While no FU mutations were found, three single nucleotide polymorphisms were identified. The expression pattern of FU was thoroughly investigated and all examined tissues express FU. It is also clear that different tissues express transcripts of different sizes and some tissues express more than one transcript. By means of nested PCR of specific regions in RT/PCR generated cDNA, it was possible to verify two alternative splicing events. This also suggests the existence of at least two additional protein isoforms besides the FU protein that has previously been described. This long FU and a much shorter isoform were compared for the ability to regulate GLI1 and GLI2. None of the FU isoforms showed any effects on GLI1 induced transcription but the long form can enhance GLI2 activity. Apparently FU did not have any effect on SUFU induced inhibition of GLI. Conclusions The FU gene and its genomic structure was identified. FU is a candidate gene for SD1, but we have not identified a pathogenic mutation in the FU coding region in a family with SD1. The sequence information and expression analyses show that transcripts of different sizes are expressed and subjected to alternative splicing

  2. Anti-HIV Ⅰ/Ⅱ Activity and Molecular Cloning of a Novel Mannose/Sialic Acid-binding Lectin from Rhizome of Polygonatum cyrtonema Hua

    Institute of Scientific and Technical Information of China (English)

    Jie AN; Jin-Ku BAO; Jin-Zhi LIU; Chuan-Fang WU; Jian LI; Lei DAI; Els Van DAMME; Jan BALZARINI; Erik De CLERCQ; Fang CHEN

    2006-01-01

    The anti-human immunodeficiency virus (HIV) Ⅰ/Ⅱ activity of a mannose and sialic acid binding lectin isolated from rhizomes of Polygonatum cyrtonema Hua was elucidated by comparing its HIV infection inhibitory activity in MT-4 and CEM cells with that of other mannose-binding lectins (MBLs). The anti-HIV activity of Polygonatum cyrtonema Hua lectin (PCL) was 10- to 100-fold more potent than other tested MBLs, but without significant cytotoxicity towards MT-4 or CEM cells. To amplify cDNA of PCL by 3'/5'-rapid amplification of cDNA ends (RACE), the 30 amino acids of N-terminal were determined by sequencing and the degenerate oligonucleotide primers were designed. The full-length cDNA of PCL contained 693 bp with an open reading frame encoding a precursor protein of 160 amino acid residues, consisting of a 28-residue signal peptide, a 22-residue C-terminal cleavage peptide and a 110-residue mature polypeptide which contained three tandemly arranged subdomains with an obvious sequence homology to the monocot MBL. However, only one active mannose-binding site (QDNVY) was found in subdomain Ⅰ of PCL, that of subdomain Ⅱ and Ⅲ changed to HNNVY and PDNVY, respectively. There was no intron in PCL, which was in good agreement with other monocot MBLs. Molecular modeling of PCL indicated that its three-dimen-sional structure resembles that of the snowdrop agglutinin. By docking, an active sialic acid-binding site was found in PCL. The instabilization of translation initiation region (TIR) in mRNA of PCL benefits its high expression in rhizomes.

  3. Proteomic shifts in embryonic stem cells with gene dose modifications suggest the presence of balancer proteins in protein regulatory networks.

    Directory of Open Access Journals (Sweden)

    Lei Mao

    Full Text Available Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of "balancer" proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the "elasticity" of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions.

  4. The cloning and expression characterization of the centrosome protein genes family (centrin genes) in rat testis

    Institute of Scientific and Technical Information of China (English)

    SUN; Xiaodong(孙晓冬); GE; Yehua(葛晔华); MA; Jing(马静); YU; Zuoren(俞作仁); LI; Sai(李赛); WANG; Yongchao(王永潮); XUE; Shepu(薛社普); HAN; Daishu(韩代书)

    2002-01-01

    Centrins are members of the centrosome protein family, which is highly conserved during revolution. The homologous genes of centrin in many organisms had been cloned, but the sequences of the rat centrin genes were not reported yet in GenBank. We cloned the cDNA fragments of centrin-1, -2 and -3 from the rat testis by RT-PCR, and analyzed the homology of the deduced amino acid sequences. The expression characterization of centrin genes in rat spermatogenesis was carried out by semi-quantitative RT-PCR. The results show that the homology of the corresponding centrin proteins in human, mouse and rat is high. The expression of centrin-1 is testis-specific, spermatogenic cell-specific and developmental stage-related. Centrin-1 begins to be transcribed when the meiosis occurs, and its mRNA level reaches the peak in round spermatids. Centrin-2 and centrin-3 are highly expressed in spermatogonia and their mRNA level decreases markedly when meiosis occurs. These results suggest that centrin-1 may play roles in meiosis and spermiogenesis, and centrin-2 and centrin-3 may be related to mitosis.

  5. PHYSIOLOGY AND GENETIC ASPECTS OF THE REGULATION OF EXPRESSION MILK PROTEIN GENES

    Directory of Open Access Journals (Sweden)

    Jozef Bulla

    2013-06-01

    Full Text Available For the genetic improvement of milk composition and milk yield, both the typing of different protein variants and knowledge about the regulation of expression of the different milk protein genes are important. Some of the processing properties of milk are dependent on the milk composition. Information about the DNA sequence and genes involved in the expression of the milk protein genes,therefore,is big importance for genetic improvement of these traits in animals breeding programmes.In recent years more data has become available concerning the regulation of expression of the milk protein genes and as might have been expected from the complex multihormonal control of these genes it appears to be rather complex. Although several mammary gland specific factors that play a role in expression of some of these genes have been identified,none of these factors has been shown to be involved in the expression of all or the majority of the milk protein genes.

  6. Systematically characterizing and prioritizing chemosensitivity related gene based on Gene Ontology and protein interaction network

    Directory of Open Access Journals (Sweden)

    Chen Xin

    2012-10-01

    Full Text Available Abstract Background The identification of genes that predict in vitro cellular chemosensitivity of cancer cells is of great importance. Chemosensitivity related genes (CRGs have been widely utilized to guide clinical and cancer chemotherapy decisions. In addition, CRGs potentially share functional characteristics and network features in protein interaction networks (PPIN. Methods In this study, we proposed a method to identify CRGs based on Gene Ontology (GO and PPIN. Firstly, we documented 150 pairs of drug-CCRG (curated chemosensitivity related gene from 492 published papers. Secondly, we characterized CCRGs from the perspective of GO and PPIN. Thirdly, we prioritized CRGs based on CCRGs’ GO and network characteristics. Lastly, we evaluated the performance of the proposed method. Results We found that CCRG enriched GO terms were most often related to chemosensitivity and exhibited higher similarity scores compared to randomly selected genes. Moreover, CCRGs played key roles in maintaining the connectivity and controlling the information flow of PPINs. We then prioritized CRGs using CCRG enriched GO terms and CCRG network characteristics in order to obtain a database of predicted drug-CRGs that included 53 CRGs, 32 of which have been reported to affect susceptibility to drugs. Our proposed method identifies a greater number of drug-CCRGs, and drug-CCRGs are much more significantly enriched in predicted drug-CRGs, compared to a method based on the correlation of gene expression and drug activity. The mean area under ROC curve (AUC for our method is 65.2%, whereas that for the traditional method is 55.2%. Conclusions Our method not only identifies CRGs with expression patterns strongly correlated with drug activity, but also identifies CRGs in which expression is weakly correlated with drug activity. This study provides the framework for the identification of signatures that predict in vitro cellular chemosensitivity and offers a valuable

  7. Altered surfactant protein A gene expression and protein homeostasis in rats with emphysematous changes

    Institute of Scientific and Technical Information of China (English)

    HU Qiong-jie; XIONG Sheng-dao; ZHANG Hui-lan; SHI Xue-mei; XU Yong-jian; ZHANG Zhen-xiang; ZHEN Guo-hua; ZHAO Jian-ping

    2008-01-01

    Background The decrease of suffactant protein(SP)secreted by the alveolar type Ⅱ cell is one of the important causes of limiting air of pulmonary emphysema.However,the SP-A gene and protein changes in this disease are rarely studied.This study was undertaken to investigate alterations in SP-A gene activity and protein,and to explore their roles in the pathogenesis of emphysematous changes.Methods Twenty Wistar rats were divided randomly into a normal control group(n=10)and a cigarette smoking(CS)+lipopolysaccharide(LPS)group(n=10).Ultra-structural changes were obsewed under an electron microscope.The number of cells positive for SP-A was measured by immunohistochemistry.The mRNA expression and protein Ievel of SP-A in the lung tissues were determined by quantitative polymerase chain reaction(qPCR)and Western blot separately.The protein level of SP-A in lavage fluid was determined by Western blot.Results The number of cells positive for SP-A of the CS+LPS group(0.35±0.03)was lower than that of the blank control group(0.72±0.06,P<0.05).The level of SP-A in the lung tissues of rats in the CS+LPS group(0.2765±0.0890)was lower than that in the blank controI group(0.6875±0.1578,P<0.05).The level of SP-A in the lavage fluid of rats in the CS+LPS group(0.8567±0.1458)was lower than that in the blank controI group(1.3541±0.2475,P<0.05).The lung tissues of rats in the CS+LPS group showed an approximate increase(0.4-fold)in SP-A mRNA levels relative to β-actin mRNA (P<0.05).Conclusions The changes of SP-A may be related to emphysematous changes in the lung.And cigarette smoke and LPS alter lung SP-A gene activity and protein homeostasis.

  8. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Esvelt, Kevin; Mali, Prashant

    2017-03-07

    Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

  9. Topology association analysis in weighted protein interaction network for gene prioritization

    Science.gov (United States)

    Wu, Shunyao; Shao, Fengjing; Zhang, Qi; Ji, Jun; Xu, Shaojie; Sun, Rencheng; Sun, Gengxin; Du, Xiangjun; Sui, Yi

    2016-11-01

    Although lots of algorithms for disease gene prediction have been proposed, the weights of edges are rarely taken into account. In this paper, the strengths of topology associations between disease and essential genes are analyzed in weighted protein interaction network. Empirical analysis demonstrates that compared to other genes, disease genes are weakly connected with essential genes in protein interaction network. Based on this finding, a novel global distance measurement for gene prioritization with weighted protein interaction network is proposed in this paper. Positive and negative flow is allocated to disease and essential genes, respectively. Additionally network propagation model is extended for weighted network. Experimental results on 110 diseases verify the effectiveness and potential of the proposed measurement. Moreover, weak links play more important role than strong links for gene prioritization, which is meaningful to deeply understand protein interaction network.

  10. Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins

    Science.gov (United States)

    Tang, Nicholas C.; Chilkoti, Ashutosh

    2016-04-01

    Most genes are synthesized using seamless assembly methods that rely on the polymerase chain reaction (PCR). However, PCR of genes encoding repetitive proteins either fails or generates nonspecific products. Motivated by the need to efficiently generate new protein polymers through high-throughput gene synthesis, here we report a codon-scrambling algorithm that enables the PCR-based gene synthesis of repetitive proteins by exploiting the codon redundancy of amino acids and finding the least-repetitive synonymous gene sequence. We also show that the codon-scrambling problem is analogous to the well-known travelling salesman problem, and obtain an exact solution to it by using De Bruijn graphs and a modern mixed integer linear programme solver. As experimental proof of the utility of this approach, we use it to optimize the synthetic genes for 19 repetitive proteins, and show that the gene fragments are amenable to PCR-based gene assembly and recombinant expression.

  11. Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins.

    Science.gov (United States)

    Tang, Nicholas C; Chilkoti, Ashutosh

    2016-04-01

    Most genes are synthesized using seamless assembly methods that rely on the polymerase chain reaction (PCR). However, PCR of genes encoding repetitive proteins either fails or generates nonspecific products. Motivated by the need to efficiently generate new protein polymers through high-throughput gene synthesis, here we report a codon-scrambling algorithm that enables the PCR-based gene synthesis of repetitive proteins by exploiting the codon redundancy of amino acids and finding the least-repetitive synonymous gene sequence. We also show that the codon-scrambling problem is analogous to the well-known travelling salesman problem, and obtain an exact solution to it by using De Bruijn graphs and a modern mixed integer linear programme solver. As experimental proof of the utility of this approach, we use it to optimize the synthetic genes for 19 repetitive proteins, and show that the gene fragments are amenable to PCR-based gene assembly and recombinant expression.

  12. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors

    DEFF Research Database (Denmark)

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M;

    2016-01-01

    tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein......The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated...... with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry...

  13. Control of Vibrio fischeri lux gene transcription by a cyclic AMP receptor protein-luxR protein regulatory circuit.

    OpenAIRE

    1988-01-01

    Expression of the Vibrio fischeri luminescence genes (lux genes) requires two transcriptional activators: the V. fischeri luxR gene product with autoinducer and the cyclic AMP (cAMP) receptor protein (CRP) with cAMP. It has been established that autoinducer and the luxR gene product are required for transcriptional activation of the luxICDABE operon, which contains a gene required for autoinducer synthesis and genes required for light emission. However, the role of cAMP-CRP in the induction o...

  14. The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders

    Science.gov (United States)

    Cattaneo, A; Cattane, N; Begni, V; Pariante, C M; Riva, M A

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders. We will discuss several mechanisms as possibly underlying BDNF modulation, including epigenetic mechanisms. We will also discuss the potential use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the factors that can influence BDNF gene expression and protein levels. Within this context, we have also characterized, for we believe the first time, the expression of BDNF transcripts in the blood, with the aim to provide novel insights into the molecular mechanisms and signaling that may regulate peripheral BDNF gene expression levels. PMID:27874848

  15. BSE case associated with prion protein gene mutation.

    Directory of Open Access Journals (Sweden)

    Jürgen A Richt

    Full Text Available Bovine spongiform encephalopathy (BSE is a transmissible spongiform encephalopathy (TSE of cattle and was first detected in 1986 in the United Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD in humans. The origin of BSE remains an enigma. Here we report an H-type BSE case associated with the novel mutation E211K within the prion protein gene (Prnp. Sequence analysis revealed that the animal with H-type BSE was heterozygous at Prnp nucleotides 631 through 633. An identical pathogenic mutation at the homologous codon position (E200K in the human Prnp has been described as the most common cause of genetic CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. A recent epidemiological study revealed that the K211 allele was not detected in 6062 cattle from commercial beef processing plants and 42 cattle breeds, indicating an extremely low prevalence of the E211K variant (less than 1 in 2000 in cattle.

  16. Protein and gene model inference based on statistical modeling in k-partite graphs.

    Science.gov (United States)

    Gerster, Sarah; Qeli, Ermir; Ahrens, Christian H; Bühlmann, Peter

    2010-07-06

    One of the major goals of proteomics is the comprehensive and accurate description of a proteome. Shotgun proteomics, the method of choice for the analysis of complex protein mixtures, requires that experimentally observed peptides are mapped back to the proteins they were derived from. This process is also known as protein inference. We present Markovian Inference of Proteins and Gene Models (MIPGEM), a statistical model based on clearly stated assumptions to address the problem of protein and gene model inference for shotgun proteomics data. In particular, we are dealing with dependencies among peptides and proteins using a Markovian assumption on k-partite graphs. We are also addressing the problems of shared peptides and ambiguous proteins by scoring the encoding gene models. Empirical results on two control datasets with synthetic mixtures of proteins and on complex protein samples of Saccharomyces cerevisiae, Drosophila melanogaster, and Arabidopsis thaliana suggest that the results with MIPGEM are competitive with existing tools for protein inference.

  17. Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae.

    Science.gov (United States)

    Müller, Axel; Severi, Emmanuele; Mulligan, Christopher; Watts, Andrew G; Kelly, David J; Wilson, Keith S; Wilkinson, Anthony J; Thomas, Gavin H

    2006-08-04

    Extracytoplasmic solute receptors (ESRs) are important components of solute uptake systems in bacteria, having been studied extensively as parts of ATP binding cassette transporters. Herein we report the first crystal structure of an ESR protein from a functionally characterized electrochemical ion gradient dependent secondary transporter. This protein, SiaP, forms part of a tripartite ATP-independent periplasmic transporter specific for sialic acid in Haemophilus influenzae. Surprisingly, the structure reveals an overall topology similar to ATP binding cassette ESR proteins, which is not apparent from the sequence, demonstrating that primary and secondary transporters can share a common structural component. The structure of SiaP in the presence of the sialic acid analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid reveals the ligand bound in a deep cavity with its carboxylate group forming a salt bridge with a highly conserved Arg residue. Sialic acid binding, which obeys simple bimolecular association kinetics as determined by stopped-flow fluorescence spectroscopy, is accompanied by domain closure about a hinge region and the kinking of an alpha-helix hinge component. The structure provides insight into the evolution, mechanism, and substrate specificity of ESR-dependent secondary transporters that are widespread in prokaryotes.

  18. RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells

    OpenAIRE

    Kariya, Yukiko; Tatsuta, Takeo; Sugawara, Shigeki; Kariya, Yoshinobu; Nitta, Kazuo; Hosono, Masahiro

    2016-01-01

    Sialic acid-binding lectin obtained from bullfrog eggs (SBL) induces cell death in cancer cells but not in normal cells. This antitumor effect is mediated through its ribo-nuclease (RNase) activity. However, the underlying molecular mechanisms remain unclear. We found that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was activated when SBL induced cell death in three human breast cancer cell lines: SK-BR-3, MCF-7, and MDA-MB231. The suppression of p38 MAPK phosphorylation...

  19. Many nonuniversal archaeal ribosomal proteins are found in conserved gene clusters

    Directory of Open Access Journals (Sweden)

    Jiachen Wang

    2009-01-01

    Full Text Available The genomic associations of the archaeal ribosomal proteins, (r-proteins, were examined in detail. The archaeal versions of the universal r-protein genes are typically in clusters similar or identical and to those found in bacteria. Of the 35 nonuniversal archaeal r-protein genes examined, the gene encoding L18e was found to be associated with the conserved L13 cluster, whereas the genes for S4e, L32e and L19e were found in the archaeal version of the spc operon. Eleven nonuniversal protein genes were not associated with any common genomic context. Of the remaining 19 protein genes, 17 were convincingly assigned to one of 10 previously unrecognized gene clusters. Examination of the gene content of these clusters revealed multiple associations with genes involved in the initiation of protein synthesis, transcription or other cellular processes. The lack of such associations in the universal clusters suggests that initially the ribosome evolved largely independently of other processes. More recently it likely has evolved in concert with other cellular systems. It was also verified that a second copy of the gene encoding L7ae found in some bacteria is actually a homolog of the gene encoding L30e and should be annotated as such.

  20. TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Mutai Hideki

    2003-06-01

    Full Text Available Abstract Background Mutations in the transmembrane cochlear expressed gene 1 (TMC1 cause deafness in human and mouse. Mutations in two homologous genes, EVER1 and EVER2 increase the susceptibility to infection with certain human papillomaviruses resulting in high risk of skin carcinoma. Here we report that TMC1, EVER1 and EVER2 (now TMC6 and TMC8 belong to a larger novel gene family, which is named TMC for trans membrane channel-like gene family. Results Using a combination of iterative database searches and reverse transcriptase-polymerase chain reaction (RT-PCR experiments we assembled contigs for cDNA encoding human, murine, puffer fish, and invertebrate TMC proteins. TMC proteins of individual species can be grouped into three subfamilies A, B, and C. Vertebrates have eight TMC genes. The majority of murine TMC transcripts are expressed in most organs; some transcripts, however, in particular the three subfamily A members are rare and more restrictively expressed. Conclusion The eight vertebrate TMC genes are evolutionary conserved and encode proteins that form three subfamilies. Invertebrate TMC proteins can also be categorized into these three subfamilies. All TMC genes encode transmembrane proteins with intracellular amino- and carboxyl-termini and at least eight membrane-spanning domains. We speculate that the TMC proteins constitute a novel group of ion channels, transporters, or modifiers of such.

  1. Absence of upregulated genes associated with protein accumulations in desmin myopathy.

    Science.gov (United States)

    Raju, Raghavan; Dalakas, Marinos C

    2007-03-01

    In desmin myopathy but not hereditary inclusion-body myopathy (hIBM), there is accumulation of myofibrillar proteins including desmin, myotilin, dystrophin, gelsolin, actin, and CDC kinase. To assess the cause of protein excess, we studied the genes coding the accumulated proteins in desmin myopathy, hIBM, and controls. No differences were found among them. In desmin myopathy, protein accumulation is not due to upregulation of genes triggered by mutant desmin, but rather to posttranslational disassembly of intermediate filaments.

  2. The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold.

    Science.gov (United States)

    Knott, Gavin J; Bond, Charles S; Fox, Archa H

    2016-05-19

    Nuclear proteins are often given a concise title that captures their function, such as 'transcription factor,' 'polymerase' or 'nuclear-receptor.' However, for members of the Drosophila behavior/human splicing (DBHS) protein family, no such clean-cut title exists. DBHS proteins are frequently identified engaging in almost every step of gene regulation, including but not limited to, transcriptional regulation, RNA processing and transport, and DNA repair. Herein, we present a coherent picture of DBHS proteins, integrating recent structural insights on dimerization, nucleic acid binding modalities and oligomerization propensity with biological function. The emerging paradigm describes a family of dynamic proteins mediating a wide range of protein-protein and protein-nucleic acid interactions, on the whole acting as a multipurpose molecular scaffold. Overall, significant steps toward appreciating the role of DBHS proteins have been made, but we are only beginning to understand the complexity and broader importance of this family in cellular biology.

  3. Dictionary and Gene Ontology Based Similarity for Named Entity Relationship Protein-protein Interaction Prediction from Biotext Corpus

    Directory of Open Access Journals (Sweden)

    Smt K. Prabavathy

    2014-12-01

    Full Text Available Protein-protein interactions functions as a significant key role in several biological systems. These involves in complex formation and many pathways which are used to perform biological processes. By accurate identification of the set of interacting proteins can get rid of new light on the functional role of various proteins in the complex surroundings of the cell. The ability to construct biologically consequential gene networks and identification of the exact relationship in the gene network is critical for present-day systems biology. In earlier research, the power of presented gene modules to shed light on the functioning of complex biological systems is studied. Most of modules in these networks have shown small link with meaningful biological function, because these methods doesn’t exactly calculate the semantic relationship between the entities. In order to overcome these problems and improve the PPI results in the biotext corpus a new method is proposed in this research. The proposed method which directly incorporates Gene Ontology (GO annotation in construction of gene modules and Dictionary-based text is proposed to extract biotext information. Dictionary-Based Text and Gene Ontology (DBTGO approach that integrates with various gene-gene pairwise similarity values, protein-protein interaction relationship obtained from gene expression, in order to gain better biotext information retrieval result. A result analysis has been carried out on Biotext Project at UC Berkley. Testing the DBTGO algorithm indicates that it is able to improve PPI relationship identification result with all previously suggested methods in terms of the precision, recall, F measure and Normalized Discounted Cumulative Gain (NDCG. The proposed DBTGO algorithm can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.

  4. Computer-aided design of modular protein devices: Boolean AND gene activation

    Science.gov (United States)

    Salis, H.; Kaznessis, Y. N.

    2006-12-01

    Many potentially useful synthetic gene networks require the expression of an engineered gene if and only if two different DNA-binding proteins exist in sufficient concentration. While some natural and engineered systems activate gene expression according to a logical AND-like behavior, they often utilize allosteric or cooperative protein-protein interactions, rendering their components unsuitable for a toolbox of modular parts for use in multiple applications. Here, we develop a quantitative model to demonstrate that a small system of interacting fusion proteins, called a protein device, can activate an engineered gene according to the Boolean AND behavior while using only modular protein domains and DNA sites. The fusion proteins are created from transactivating, DNA-binding, non-DNA binding, and protein-protein interaction domains along with the corresponding peptide ligands. Using a combined kinetic and thermodynamic model, we identify the characteristics of the molecular components and their rates of constitutive production that maximize the fidelity of AND behavior. These AND protein devices facilitate the creation of complex genetic programs and may be used to create gene therapies, biosensors and other biomedical and biotechnological applications that turn on gene expression only when multiple DNA-binding proteins are simultaneously present.

  5. Plant protein kinase genes induced by drought, high salt and cold stresses

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Drought, high salt and cold are three different kinds of environment stresses that severely influence the growth, development and productivity of crops. They all decrease the water state of plant cells, and consequently result in the harm of plant from water deficit. Several genes encoding protein kinases and induced by drought, high salt and low temperature have been isolated from Arabidopsis. These protein kinases include receptor protein kinase (RPK), MAP kinases, ribosomal-protein kinases and transcription-regulation protein kinase. The expression features of these genes and the regulatory roles of these protein kinases in stress response and signal transduction are discussed.

  6. Centrin protein and genes in Trichomonas vaginalis and close relatives.

    Science.gov (United States)

    Brugerolle, G; Bricheux, G; Coffe, G

    2000-01-01

    Anti-centrin monoclonal antibodies 20H5 and 11B2 produced against Clamydomononas centrin decorated the group of basal bodies as well as very closely attached structures in all trichomonads studied and in the devescovinids Foaina and Devescovina. Moreover, these antibodies decorated the undulating membrane in Trichomonas vaginalis, Trichomitus batrachorum, and Tritrichomonas foetus, and the cresta in Foaina. Centrin was not demonstrated in the dividing spindle and paradesmosis. Immunogold labeling, both in pre- and post-embedding, confirmed that centrin is associated with the basal body cylinder and is a component of the nine anchoring arms between the terminal plate of flagellar bases and the plasma-membrane. Centrin is also associated with the hook-shaped fibers attached to basal bodies (F1, F3), the X-fiber, and along sigmoid fibers (F2) at the pelta-axostyle junction, which is the microtubule organizing center for pelta-axostyle microtubules. There was no labeling on the striated costa and parabasal fibers nor on microtubular pelta-axostyle, but the fibrous structure inside the undulating membrane was labeled in T. vaginalis. Two proteins of 22-20 kDa corresponding to the centrin molecular mass were recognized by immunoblotting using these antibodies in the three trichomonad species examined. By screening a T. vaginalis cDNA library with 20H5 antibody, two genes encoding identical protein sequences were found. The sequence comprises the 4 typical EF-hand Ca++-binding domains present in every known centrin. Trichomonad centrin is closer to the green algal cluster (70% identity) than to the yeast Cdc31 cluster (55% identity) or the Alveolata cluster (46% identity).

  7. BindUP: a web server for non-homology-based prediction of DNA and RNA binding proteins.

    Science.gov (United States)

    Paz, Inbal; Kligun, Efrat; Bengad, Barak; Mandel-Gutfreund, Yael

    2016-07-08

    Gene expression is a multi-step process involving many layers of regulation. The main regulators of the pathway are DNA and RNA binding proteins. While over the years, a large number of DNA and RNA binding proteins have been identified and extensively studied, it is still expected that many other proteins, some with yet another known function, are awaiting to be discovered. Here we present a new web server, BindUP, freely accessible through the website http://bindup.technion.ac.il/, for predicting DNA and RNA binding proteins using a non-homology-based approach. Our method is based on the electrostatic features of the protein surface and other general properties of the protein. BindUP predicts nucleic acid binding function given the proteins three-dimensional structure or a structural model. Additionally, BindUP provides information on the largest electrostatic surface patches, visualized on the server. The server was tested on several datasets of DNA and RNA binding proteins, including proteins which do not possess DNA or RNA binding domains and have no similarity to known nucleic acid binding proteins, achieving very high accuracy. BindUP is applicable in either single or batch modes and can be applied for testing hundreds of proteins simultaneously in a highly efficient manner.

  8. Autogenous Regulation of Splicing of the Transcript of a Yeast Ribosomal Protein Gene

    Science.gov (United States)

    Dabeva, Mariana D.; Post-Beittenmiller, Martha A.; Warner, Jonathan R.

    1986-08-01

    The gene for a yeast ribosomal protein, RPL32, contains a single intron. The product of this gene appears to participate in feedback control of the splicing of the intron from the transcript. This autogenous regulation of splicing provides a striking analogy to the autogenous regulation of translation of ribosomal proteins in Escherichia coli.

  9. A Hox Gene, Antennapedia, Regulates Expression of Multiple Major Silk Protein Genes in the Silkworm Bombyx mori.

    Science.gov (United States)

    Tsubota, Takuya; Tomita, Shuichiro; Uchino, Keiro; Kimoto, Mai; Takiya, Shigeharu; Kajiwara, Hideyuki; Yamazaki, Toshimasa; Sezutsu, Hideki

    2016-03-25

    Hoxgenes play a pivotal role in the determination of anteroposterior axis specificity during bilaterian animal development. They do so by acting as a master control and regulating the expression of genes important for development. Recently, however, we showed that Hoxgenes can also function in terminally differentiated tissue of the lepidopteranBombyx mori In this species,Antennapedia(Antp) regulates expression of sericin-1, a major silk protein gene, in the silk gland. Here, we investigated whether Antpcan regulate expression of multiple genes in this tissue. By means of proteomic, RT-PCR, and in situ hybridization analyses, we demonstrate that misexpression of Antpin the posterior silk gland induced ectopic expression of major silk protein genes such assericin-3,fhxh4, and fhxh5 These genes are normally expressed specifically in the middle silk gland as is Antp Therefore, the evidence strongly suggests that Antpactivates these silk protein genes in the middle silk gland. The putativesericin-1 activator complex (middle silk gland-intermolt-specific complex) can bind to the upstream regions of these genes, suggesting that Antpdirectly activates their expression. We also found that the pattern of gene expression was well conserved between B. moriand the wild species Bombyx mandarina, indicating that the gene regulation mechanism identified here is an evolutionarily conserved mechanism and not an artifact of the domestication of B. mori We suggest that Hoxgenes have a role as a master control in terminally differentiated tissues, possibly acting as a primary regulator for a range of physiological processes.

  10. Construction of plant expression vector of Pseudopleuronectes americanus antifreeze protein gene

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The Pseudopleuronectes americanus antifreeze protein gene was synthesized and control sequences were added such as 35S promoter and nos terminator that can facilitate the transcription and fi sequence and Kozak sequence that can improve the expression in translation level, the high expression cassette of antifreeze protein was constructed. This cassette was connected to pBI121.1 and finally got the high expression vector pBRTSAFP introduced into the maize callus. The expression of gus gene that linked to the antifreeze protein gene was detected, and the results was that the gus gene can express strongly and instantaneously.

  11. Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    E.A. Croes (Esther); B.Z. Alizadeh (Behrooz); A.M. Bertoli Avella (Aida); T.A.M. Rademaker (Tessa); J. Vergeer-Drop (Jeannette); B. Dermaut (Bart); J.J. Houwing-Duistermaat (Jeanine); D.P.W.M. Wientjens (Dorothee); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cock)

    2004-01-01

    textabstractThe prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the prion protein production as well as polymorphisms in

  12. Wool Keratin-Associated Protein Genes in Sheep-A Review.

    Science.gov (United States)

    Gong, Hua; Zhou, Huitong; Forrest, Rachel H J; Li, Shaobin; Wang, Jiqing; Dyer, Jolon M; Luo, Yuzhu; Hickford, Jon G H

    2016-05-28

    The importance of sheep's wool in making textiles has inspired extensive research into its structure and the underlying genetics since the 1960s. Wool keratin-associated proteins (KAPs) are a key structural component of the wool fibre. The characterisation of the genes encoding these proteins has progressed rapidly with advances in the nucleotide and protein sequencing. This review describes our knowledge of ovine KAPs, their categorisation into families, polymorphism in the proteins and genes, the clustering and chromosomal location of the genes, some characteristics of gene expression and some potential effects of the KAPs on wool traits. The extent and nature of genetic variation in wool KAP genes and its association with fibre characteristics, provides an opportunity for the development of gene-markers for selective breeding of sheep to produce better wool with properties highly matched to specific end-uses.

  13. Wool Keratin-Associated Protein Genes in Sheep—A Review

    Science.gov (United States)

    Gong, Hua; Zhou, Huitong; Forrest, Rachel H. J.; Li, Shaobin; Wang, Jiqing; Dyer, Jolon M.; Luo, Yuzhu; Hickford, Jon G. H.

    2016-01-01

    The importance of sheep’s wool in making textiles has inspired extensive research into its structure and the underlying genetics since the 1960s. Wool keratin-associated proteins (KAPs) are a key structural component of the wool fibre. The characterisation of the genes encoding these proteins has progressed rapidly with advances in the nucleotide and protein sequencing. This review describes our knowledge of ovine KAPs, their categorisation into families, polymorphism in the proteins and genes, the clustering and chromosomal location of the genes, some characteristics of gene expression and some potential effects of the KAPs on wool traits. The extent and nature of genetic variation in wool KAP genes and its association with fibre characteristics, provides an opportunity for the development of gene-markers for selective breeding of sheep to produce better wool with properties highly matched to specific end-uses. PMID:27240405

  14. Regeneration of transgenic plants of Prunus armeniaca containing the coat protein gene of Plum Pox Virus.

    Science.gov (United States)

    da Câmara Machado, M L; da Câmara Machado, A; Hanzer, V; Weiss, H; Regner, F; Steinkellner, H; Mattanovich, D; Plail, R; Knapp, E; Kalthoff, B; Katinger, H

    1992-02-01

    A system was developed which allows the transfer of foreign genes into apricot cultivars. We report the transformation and regeneration of Prunus armeniaca plants with Agrobacterium tumefaciens strain LBA 4404 containing various binary plasmids, pBinGUSint, carrying the marker gene ß-glucuronidase (GUS) and pBinPPVm, carrying the coat protein gene of Plum Pox Virus (PPV). The marker gene GUS was used for optical evaluation of the efficiency of the transformation system. The coat protein gene of PPV was used to introduce coat protein mediated resistance against one of the most important pathogens of stone fruit trees in Europe and the whole Mediterranean area. This is the first report of the successful integration of a viral coat protein gene into a fruit tree species, opening a new perspective on the control of the disease.

  15. A plethora of plant serine/arginine-rich proteins: redundancy or evolution of novel gene functions?

    Science.gov (United States)

    Kalyna, Maria; Barta, Andrea

    2017-01-01

    Pre-mRNA processing is an important step in gene expression and its regulation leads to the expansion of the gene product repertoire. Serine/arginine-rich (SR) proteins are key players in intron recognition and spliceosome assembly and contribute significantly to the alternative splicing process. Due to several duplication events, at least 19 SR proteins are present in the Arabidopsis genome which is almost twice as much as in humans. They fall into seven different subfamilies, three of them homologous to metazoan splicing factors whereas the other four seem to be specific for plants. The current data show that most duplicated genes have different spatio-temporal expression patterns indicating functional diversification. Interestingly, the majority of SR protein genes are alternatively spliced and in some cases this process was shown to be under developmental and/or environmental control. This might greatly influence gene expression of target genes as also exemplified by ectopic expression studies of particular SR proteins. PMID:15270675

  16. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel;

    2015-01-01

    IP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression...... at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes...

  17. Prioritizing cancer-related genes with aberrant methylation based on a weighted protein-protein interaction network

    Directory of Open Access Journals (Sweden)

    Lv Jie

    2011-10-01

    Full Text Available Abstract Background As an important epigenetic modification, DNA methylation plays a crucial role in the development of mammals and in the occurrence of complex diseases. Genes that interact directly or indirectly may have the same or similar functions in the biological processes in which they are involved and together contribute to the related disease phenotypes. The complicated relations between genes can be clearly represented using network theory. A protein-protein interaction (PPI network offers a platform from which to systematically identify disease-related genes from the relations between genes with similar functions. Results We constructed a weighted human PPI network (WHPN using DNA methylation correlations based on human protein-protein interactions. WHPN represents the relationships of DNA methylation levels in gene pairs for four cancer types. A cancer-associated subnetwork (CASN was obtained from WHPN by selecting genes associated with seed genes which were known to be methylated in the four cancers. We found that CASN had a more densely connected network community than WHPN, indicating that the genes in CASN were much closer to seed genes. We prioritized 154 potential cancer-related genes with aberrant methylation in CASN by neighborhood-weighting decision rule. A function enrichment analysis for GO and KEGG indicated that the optimized genes were mainly involved in the biological processes of regulating cell apoptosis and programmed cell death. An analysis of expression profiling data revealed that many of the optimized genes were expressed differentially in the four cancers. By examining the PubMed co-citations, we found 43 optimized genes were related with cancers and aberrant methylation, and 10 genes were validated to be methylated aberrantly in cancers. Of 154 optimized genes, 27 were as diagnostic markers and 20 as prognostic markers previously identified in literature for cancers and other complex diseases by searching Pub

  18. Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling

    Directory of Open Access Journals (Sweden)

    Mo Min

    2008-05-01

    Full Text Available Abstract Background The polyadenylation of mRNA is one of the critical processing steps during expression of almost all eukaryotic genes. It is tightly integrated with transcription, particularly its termination, as well as other RNA processing events, i.e. capping and splicing. The poly(A tail protects the mRNA from unregulated degradation, and it is required for nuclear export and translation initiation. In recent years, it has been demonstrated that the polyadenylation process is also involved in the regulation of gene expression. The polyadenylation process requires two components, the cis-elements on the mRNA and a group of protein factors that recognize the cis-elements and produce the poly(A tail. Here we report a comprehensive pairwise protein-protein interaction mapping and gene expression profiling of the mRNA polyadenylation protein machinery in Arabidopsis. Results By protein sequence homology search using human and yeast polyadenylation factors, we identified 28 proteins that may be components of Arabidopsis polyadenylation machinery. To elucidate the protein network and their functions, we first tested their protein-protein interaction profiles. Out of 320 pair-wise protein-protein interaction assays done using the yeast two-hybrid system, 56 (~17% showed positive interactions. 15 of these interactions were further tested, and all were confirmed by co-immunoprecipitation and/or in vitro co-purification. These interactions organize into three distinct hubs involving the Arabidopsis polyadenylation factors. These hubs are centered around AtCPSF100, AtCLPS, and AtFIPS. The first two are similar to complexes seen in mammals, while the third one stands out as unique to plants. When comparing the gene expression profiles extracted from publicly available microarray datasets, some of the polyadenylation related genes showed tissue-specific expression, suggestive of potential different polyadenylation complex configurations. Conclusion An

  19. Molecular characterisation of the nucleocapsid protein gene, glycoprotein gene and gene junctions of rhabdovirus 903/87, a novel fish pathogenic rhabdovirus

    DEFF Research Database (Denmark)

    Johansson, Tove; Nylund, S.; Olesen, Niels Jørgen

    2001-01-01

    The sequences of the nucleocapsid and glycoprotein genes and the gene junctions of the fish pathogenic rhabdovirus 903/87 were determined from cDNA and PCR clones. The mRNA of the nucleocapsid is most likely 1492 nucleotides long and encodes a protein of 426 amino acids, whereas the mRNA of the g......The sequences of the nucleocapsid and glycoprotein genes and the gene junctions of the fish pathogenic rhabdovirus 903/87 were determined from cDNA and PCR clones. The mRNA of the nucleocapsid is most likely 1492 nucleotides long and encodes a protein of 426 amino acids, whereas the m...

  20. Concerted evolution of duplicated protein-coding genes in Drosophila.

    Science.gov (United States)

    Hickey, D A; Bally-Cuif, L; Abukashawa, S; Payant, V; Benkel, B F

    1991-03-01

    Very rapid rates of gene conversion were observed between duplicated alpha-amylase-coding sequences in Drosophila melanogaster. This gene conversion process was also seen in the related species Drosophila erecta. Specifically, there is virtual sequence identity between the coding regions of the two genes within each species, while the sequence divergence between species is close to that expected based on their phylogenetic relationship. The flanking, noncoding regions are much more highly diverged and do not appear to be subject to gene conversion. Comparison of amylase sequences between the two species provides a clear demonstration that recurrent gene conversion does indeed lead to the concerted evolution of the gene pair.

  1. Identification of Genes Encoding the Folate- and Thiamine-Binding Membrane Proteins in Firmicutes

    NARCIS (Netherlands)

    Eudes, Aymerick; Erkens, Guus B.; Slotboom, Dirk J.; Rodionov, Dmitry A.; Naponelli, Valeria; Hanson, Andrew D.

    2008-01-01

    Genes encoding high-affinity folate- and thiamine-binding proteins (FolT, ThiT) were identified in the Lactobacillus casei genome, expressed in Lactococcus lactis, and functionally characterized. Similar genes occur in many Firmicutes, sometimes next to folate or thiamine salvage genes. Most thiT ge

  2. Trithorax group proteins: switching genes on and keeping them active.

    Science.gov (United States)

    Schuettengruber, Bernd; Martinez, Anne-Marie; Iovino, Nicola; Cavalli, Giacomo

    2011-11-23

    Cellular memory is provided by two counteracting groups of chromatin proteins termed Trithorax group (TrxG) and Polycomb group (PcG) proteins. TrxG proteins activate transcription and are perhaps best known because of the involvement of the TrxG protein MLL in leukaemia. However, in terms of molecular analysis, they have lived in the shadow of their more famous counterparts, the PcG proteins. Recent advances have improved our understanding of TrxG protein function and demonstrated that the heterogeneous group of TrxG proteins is of critical importance in the epigenetic regulation of the cell cycle, senescence, DNA damage and stem cell biology.

  3. Synonymous codon usage in different protein secondary structural classes of human genes: Implication for increased non-randomness of GC3 rich genes towards protein stability

    Indian Academy of Sciences (India)

    Pamela Mukhopadhyay; Surajit Basak; Tapash Chandra Ghosh

    2007-08-01

    The relationship between the synonymous codon usage and different protein secondary structural classes were investigated using 401 Homo sapiens proteins extracted from Protein Data Bank (PDB). A simple Chi-square test was used to assess the significance of deviation of the observed and expected frequencies of 59 codons at the level of individual synonymous families in the four different protein secondary structural classes. It was observed that synonymous codon families show non-randomness in codon usage in four different secondary structural classes. However, when the genes were classified according to their GC3 levels there was an increase in non-randomness in high GC3 group of genes. The non-randomness in codon usage was further tested among the same protein secondary structures belonging to four different protein folding classes of high GC3 group of genes. The results show that in each of the protein secondary structural unit there exist some synonymous family that shows class specific codonusage pattern. Moreover, there is an increased non-random behaviour of synonymous codons in sheet structure of all secondary structural classes in high GC3 group of genes. Biological implications of these results have been discussed.

  4. PCR-based gene synthesis to produce recombinant proteins for crystallization

    Directory of Open Access Journals (Sweden)

    Byrne-Steele Miranda L

    2008-04-01

    Full Text Available Abstract Background Gene synthesis technologies are an important tool for structural biology projects, allowing increased protein expression through codon optimization and facilitating sequence alterations. Existing methods, however, can be complex and not always reproducible, prompting researchers to use commercial suppliers rather than synthesize genes themselves. Results A PCR-based gene synthesis method, referred to as SeqTBIO, is described to efficiently assemble the coding regions of two novel hyperthermophilic proteins, PAZ (Piwi/Argonaute/Zwille domain, a siRNA-binding domain of an Argonaute protein homologue and a deletion mutant of a family A DNA polymerase (PolA. The gene synthesis procedure is based on sequential assembly such that homogeneous DNA products can be obtained after each synthesis step without extensive manipulation or purification requirements. Coupling the gene synthesis procedure to in vivo homologous recombination techniques allows efficient subcloning and site-directed mutagenesis for error correction. The recombinant proteins of PAZ and PolA were subsequently overexpressed in E. coli and used for protein crystallization. Crystals of both proteins were obtained and they were suitable for X-ray analysis. Conclusion We demonstrate, by using PAZ and PolA as examples, the feasibility of integrating the gene synthesis, error correction and subcloning techniques into a non-automated gene to crystal pipeline such that genes can be designed, synthesized and implemented for recombinant expression and protein crystallization.

  5. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

    Science.gov (United States)

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J; Sirota, Marina

    2016-05-04

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.

  6. Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene

    DEFF Research Database (Denmark)

    Sun, C; Van Ghelue, M; Tranebjaerg, L;

    2010-01-01

    Sun C, Van Ghelue M, Tranebjaerg L, Thyssen F, Nilssen Ø, Torbergsen T. Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene. Myotonia is characterized by hyperexcitability of the muscle cell membrane. Myotonic disorders...... channel genes SCN4A and CLCN1, the myotonic dystrophy protein kinase (DMPK) gene, and the CCHC-type zinc finger, nucleic acid binding protein gene CNBP. Additional gene(s) and/or modifying factor(s) remain to be identified. In this study, we investigated a large Norwegian family with clinically different...... presentations of myotonic disorders. Molecular analysis revealed CCTG repeat expansions in the CNBP gene in all affected members, confirming that they have myotonic dystrophy type 2. However, a CLCN1 mutation c.1238C>G, causing p.Phe413Cys, was also identified in several affected family members. Heterozygosity...

  7. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    Science.gov (United States)

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

    2016-11-01

    The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.

  8. Gene cloning and prokaryotic expression of recombinant outer membrane protein from Vibrio parahaemolyticus

    Science.gov (United States)

    Yuan, Ye; Wang, Xiuli; Guo, Sheping; Qiu, Xuemei

    2011-06-01

    Gram-negative Vibrio parahaemolyticus is a common pathogen in humans and marine animals. The outer membrane protein of bacteria plays an important role in the infection and pathogenicity to the host. Thus, the outer membrane proteins are an ideal target for vaccines. We amplified a complete outer membrane protein gene (ompW) from V. parahaemolyticus ATCC 17802. We then cloned and expressed the gene into Escherichia coli BL21 (DE3) cells. The gene coded for a protein that was 42.78 kDa. We purified the protein using Ni-NTA affinity chromatography and Anti-His antibody Western blotting, respectively. Our results provide a basis for future application of the OmpW protein as a vaccine candidate against infection by V. parahaemolyticus. In addition, the purified OmpW protein can be used for further functional and structural studies.

  9. Connecting protein and mRNA burst distributions for stochastic models of gene expression

    CERN Document Server

    Elgart, Vlad; Fenley, Andrew T; Kulkarni, Rahul V

    2011-01-01

    The intrinsic stochasticity of gene expression can lead to large variability in protein levels for genetically identical cells. Such variability in protein levels can arise from infrequent synthesis of mRNAs which in turn give rise to bursts of protein expression. Protein expression occurring in bursts has indeed been observed experimentally and recent studies have also found evidence for transcriptional bursting, i.e. production of mRNAs in bursts. Given that there are distinct experimental techniques for quantifying the noise at different stages of gene expression, it is of interest to derive analytical results connecting experimental observations at different levels. In this work, we consider stochastic models of gene expression for which mRNA and protein production occurs in independent bursts. For such models, we derive analytical expressions connecting protein and mRNA burst distributions which show how the functional form of the mRNA burst distribution can be inferred from the protein burst distributio...

  10. Gene cloning and prokaryotic expression of recombinant outer membrane protein from Vibrio parahaemolyticus

    Institute of Scientific and Technical Information of China (English)

    YUAN Ye; WANG Xiuli; GUO Sheping; QIU xuemei

    2011-01-01

    Gram-negative vibrio parahaemolyticus is a common pathogen in humans and marine animals.The outer membrane protein of bacteria plays an important role in the infection and pathogenicity to the host.Thus,the outer membrane proteins are an ideal target for vaccines.We amplified a complete outer membrane protein gene (ompW) from V.parahaemolyticus ATCC 17802.We then cloned and expressed the gene into Escherichia coli BL21 (DE3) cells.The gene coded for a protein that was 42.78 kDa.We purified the protein using Ni-NTA affinity chromatography and Anti-His antibody Western blotting,respectively.Our results provide a basis for future application of the OmpW protein as a vaccine candidate against infection by V.parahaemolyticus.In addition,the purified OmpW protein can be used for further functional and structural studies.

  11. Gene-specific correlation of RNA and protein levels in human cells and tissues

    DEFF Research Database (Denmark)

    Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M.

    2016-01-01

    An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring...... to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP...

  12. Expression of Yes-associated protein 1 gene and protein in oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Song-ying; HU Ji-an; WANG Hui-ming

    2013-01-01

    Background Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the oral and maxillofaoial region.Yes-associated protein 1 (YAP1) has been implicated as a bona fide oncogene in solid tumors.We seek to elucidate the role of YAP1 in OSCC tissue.Methods We identified YAP1 gene and protein overexpression in 30 OSCC patients and 10 normal oral mucosa tissues by immunohistochemistry,Western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results In the normal oral mucosa by immunohistochemical staining,YAP1 mainly located in both the cytoplasm and nucleus mainly the nuclei of the basal cells.In OSCC,the expression of YAP1 translocated from the nucleus to cytoplasm;YAP1 being mainly located in both the cytoplasm and nucleus of the adjacent mucosa.The expression of YAP1 gradual increased in normal oral mucosa,tumor adjacent mucosa and low grade,middle grade,high grade OSCC tissue by Western blotting.Significant difference was found between the expressions of the normal oral mucosa and OSCC tissue (P <0.05).The coincidence was detected between the normal oral mucosa and OSCC tissue by RT-PCR (P <0.05).Conclusions YAP1 is involved in the carcinogenesis and development of OSCC.There is a transformation between nucleus and cytoplasm.

  13. Phylogenetic Analysis of Homologous Proteins Encoded by UL2 and UL23 genes of Herpesviridae

    Institute of Scientific and Technical Information of China (English)

    Long-ding LIU; Wen-juan WU; Min HONG; Hai-jing SHI; Shao-hui MA; Jing-jing WANG; Hong-ling ZHAO; Yun LIAO; Qi-han LI

    2007-01-01

    The proteins encoded by the Herpesviridae β-gene play a critical role in the replication stage of the virus. In this paper, phylogenetic analyses provided evidence that someβ-gene products, such as UL2 and UL23 from HSV1, have their homologous genes in its family, and also exist in prokaryotic organisms, indicating that these viruses appear to have been assembled over evolutionary time by numerous independent events of horizontal gene transfer.

  14. MYB elongation is regulated by the nucleic acid binding of NFκB p50 to the intronic stem-loop region.

    Directory of Open Access Journals (Sweden)

    Lloyd A Pereira

    Full Text Available MYB transcriptional elongation is regulated by an attenuator sequence within intron 1 that has been proposed to encode a RNA stem loop (SLR followed by a polyU tract. We report that NFκBp50 can bind the SLR polyU RNA and promote MYB transcriptional elongation together with NFκBp65. We identified a conserved lysine-rich motif within the Rel homology domain (RHD of NFκBp50, mutation of which abrogated the interaction of NFκBp50 with the SLR polyU and impaired NFκBp50 mediated MYB elongation. We observed that the TAR RNA-binding region of Tat is homologous to the NFκBp50 RHD lysine-rich motif, a finding consistent with HIV Tat acting as an effector of MYB transcriptional elongation in an SLR dependent manner. Furthermore, we identify the DNA binding activity of NFκBp50 as a key component required for the SLR polyU mediated regulation of MYB. Collectively these results suggest that the MYB SLR polyU provides a platform for proteins to regulate MYB and reveals novel nucleic acid binding properties of NFκBp50 required for MYB regulation.

  15. In silicio search for genes encoding peroxisomal proteins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kal, A J; Hettema, E H; van den Berg, M; Koerkamp, M G; van Ijlst, L; Distel, B; Tabak, H F

    2000-01-01

    The biogenesis of peroxisomes involves the synthesis of new proteins that after, completion of translation, are targeted to the organelle by virtue of peroxisomal targeting signals (PTS). Two types of PTSs have been well characterized for import of matrix proteins (PTS1 and PTS2). Induction of the genes encoding these matrix proteins takes place in oleate-containing medium and is mediated via an oleate response element (ORE) present in the region preceding these genes. The authors have searched the yeast genome for OREs preceding open reading frames (ORFs), and for ORFs that contain either a PTS1 or PTS2. Of the ORFs containing an ORE, as well as either a PTS1 or a PTS2, many were known to encode bona fide peroxisomal matrix proteins. In addition, candidate genes were identified as encoding putative new peroxisomal proteins. For one case, subcellular location studies validated the in silicio prediction. This gene encodes a new peroxisomal thioesterase.

  16. Revisiting the missing protein-coding gene catalog of the domestic dog

    Directory of Open Access Journals (Sweden)

    Galibert Francis

    2009-02-01

    Full Text Available Abstract Background Among mammals for which there is a high sequence coverage, the whole genome assembly of the dog is unique in that it predicts a low number of protein-coding genes, ~19,000, compared to the over 20,000 reported for other mammalian species. Of particular interest are the more than 400 of genes annotated in primates and rodent genomes, but missing in dog. Results Using over 14,000 orthologous genes between human, chimpanzee, mouse rat and dog, we built multiple pairwise synteny maps to infer short orthologous intervals that were targeted for characterizing the canine missing genes. Based on gene prediction and a functionality test using the ratio of replacement to silent nucleotide substitution rates (dN/dS, we provide compelling structural and functional evidence for the identification of 232 new protein-coding genes in the canine genome and 69 gene losses, characterized as undetected gene or pseudogenes. Gene loss phyletic pattern analysis using ten species from chicken to human allowed us to characterize 28 canine-specific gene losses that have functional orthologs continuously from chicken or marsupials through human, and 10 genes that arose specifically in the evolutionary lineage leading to rodent and primates. Conclusion This study demonstrates the central role of comparative genomics for refining gene catalogs and exploring the evolutionary history of gene repertoires, particularly as applied for the characterization of species-specific gene gains and losses.

  17. ANDROGEN REGULATION OF PROSTATIC STEROID BINDING PROTEIN GENE TRANSCRIPTION

    Institute of Scientific and Technical Information of China (English)

    ZHANGYong-Lian; ZHOUZong-Xun; ZHANGYou-Duan; PARKERMalcolmG

    1989-01-01

    Prostatic steroid binding protein (PSBP) is a major protein secreted in the rat ventral prostate (V.P.) and also one of the components in seminal fluid, The potential importance of this protein in male fertility emerged from its ability of binding cholesterol which might modulate the proportion of phospholipids and cholesterol in sperm making it suitable

  18. Comparative study of human mitochondrial proteome reveals extensive protein subcellular relocalization after gene duplications

    Directory of Open Access Journals (Sweden)

    Huang Yong

    2009-11-01

    Full Text Available Abstract Background Gene and genome duplication is the principle creative force in evolution. Recently, protein subcellular relocalization, or neolocalization was proposed as one of the mechanisms responsible for the retention of duplicated genes. This hypothesis received support from the analysis of yeast genomes, but has not been tested thoroughly on animal genomes. In order to evaluate the importance of subcellular relocalizations for retention of duplicated genes in animal genomes, we systematically analyzed nuclear encoded mitochondrial proteins in the human genome by reconstructing phylogenies of mitochondrial multigene families. Results The 456 human mitochondrial proteins selected for this study were clustered into 305 gene families including 92 multigene families. Among the multigene families, 59 (64% consisted of both mitochondrial and cytosolic (non-mitochondrial proteins (mt-cy families while the remaining 33 (36% were composed of mitochondrial proteins (mt-mt families. Phylogenetic analyses of mt-cy families revealed three different scenarios of their neolocalization following gene duplication: 1 relocalization from mitochondria to cytosol, 2 from cytosol to mitochondria and 3 multiple subcellular relocalizations. The neolocalizations were most commonly enabled by the gain or loss of N-terminal mitochondrial targeting signals. The majority of detected subcellular relocalization events occurred early in animal evolution, preceding the evolution of tetrapods. Mt-mt protein families showed a somewhat different pattern, where gene duplication occurred more evenly in time. However, for both types of protein families, most duplication events appear to roughly coincide with two rounds of genome duplications early in vertebrate evolution. Finally, we evaluated the effects of inaccurate and incomplete annotation of mitochondrial proteins and found that our conclusion of the importance of subcellular relocalization after gene duplication on

  19. Absence of repellents in Ustilago maydis induces genes encoding small secreted proteins.

    Science.gov (United States)

    Teertstra, Wieke R; Krijgsheld, Pauline; Wösten, Han A B

    2011-08-01

    The rep1 gene of the maize pathogen Ustilago maydis encodes a pre-pro-protein that is processed in the secretory pathway into 11 peptides. These so-called repellents form amphipathic amyloid fibrils at the surface of aerial hyphae. A SG200 strain in which the rep1 gene is inactivated (∆rep1 strain) is affected in aerial hyphae formation. We here assessed changes in global gene expression as a consequence of the inactivation of the rep1 gene. Microarray analysis revealed that only 31 genes in the ∆rep1 SG200 strain had a fold change in expression of ≥2. Twenty-two of these genes were up-regulated and half of them encode small secreted proteins (SSPs) with unknown functions. Seven of the SSP genes and two other genes that are over-expressed in the ∆rep1 SG200 strain encode proteins that can be classified as secreted cysteine-rich proteins (SCRPs). Interestingly, most of the SCRPs are predicted to form amyloids. The SCRP gene um00792 showed the highest up-regulation in the ∆rep1 strain. Using GFP as a reporter, it was shown that this gene is over-expressed in the layer of hyphae at the medium-air interface. Taken together, it is concluded that inactivation of rep1 hardly affects the expression profile of U. maydis, despite the fact that the mutant strain has a strong reduced ability to form aerial hyphae.

  20. Improved gene expression signature of testicular carcinoma in situ

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Leffers, Henrik; Lothe, Ragnhild A;

    2007-01-01

    on global gene expression in testicular CIS have been previously published. We have merged the two data sets on CIS samples (n = 6) and identified the shared gene expression signature in relation to expression in normal testis. Among the top-20 highest expressed genes, one-third was transcription factors...... and the list included some 'novel' CIS markers (i.e. DOCK11 and ANXA3). Genes related to biological terms 'nucleic acid binding' and 'translational activity' (e.g. transcription factors and ribosomal proteins, respectively) were consistently and significantly over-represented. Some of the significantly over......-expressed genes in CIS cells were selected for validation by RT-PCR (IFI16, DOCK11, and ANXA3), immunohistochemistry (HLXB9), or in situ hybridization (IFI16). High-level analysis utilizing the Ingenuity pathway analysis tool indicated that networks relating to 'gene expression in cancer' and 'embryonic...

  1. Concerted evolution of duplicated protein-coding genes in Drosophila.

    OpenAIRE

    Hickey, D. A.; Bally-Cuif, L.; Abukashawa, S; Payant, V; Benkel, B F

    1991-01-01

    Very rapid rates of gene conversion were observed between duplicated alpha-amylase-coding sequences in Drosophila melanogaster. This gene conversion process was also seen in the related species Drosophila erecta. Specifically, there is virtual sequence identity between the coding regions of the two genes within each species, while the sequence divergence between species is close to that expected based on their phylogenetic relationship. The flanking, noncoding regions are much more highly div...

  2. A positive feedback-based gene circuit to increase the production of a membrane protein

    Directory of Open Access Journals (Sweden)

    Gennis Robert B

    2010-05-01

    Full Text Available Abstract Background Membrane proteins are an important class of proteins, playing a key role in many biological processes, and are a promising target in pharmaceutical development. However, membrane proteins are often difficult to produce in large quantities for the purpose of crystallographic or biochemical analyses. Results In this paper, we demonstrate that synthetic gene circuits designed specifically to overexpress certain genes can be applied to manipulate the expression kinetics of a model membrane protein, cytochrome bd quinol oxidase in E. coli, resulting in increased expression rates. The synthetic circuit involved is an engineered, autoinducer-independent variant of the lux operon activator LuxR from V. fischeri in an autoregulatory, positive feedback configuration. Conclusions Our proof-of-concept experiments indicate a statistically significant increase in the rate of production of the bd oxidase membrane protein. Synthetic gene networks provide a feasible solution for the problem of membrane protein production.

  3. CLONING SEGMENT SPIKE PROTEIN GENE OF SARS-COV AND ITS EXPRESSION IN ESCHERICHIA COLI

    Institute of Scientific and Technical Information of China (English)

    刘中华; 许文波; 毛乃颖; 张燕; 朱贞; 崔爱利; 杨建国; 胡海涛

    2004-01-01

    Objective Expressing and purifying the segment of SARS-CoV spike protein in E.Coli. Methods The target gene was obtained by RT-PCR. The PCR product was cloned into pEGM- T Easy Vector, sequencing and double restriction digestion ( BamHⅠ,PstⅠ) were performed. The target gene was subcloned into PQE30 expression vector. The gene was expressed in the E.coli strain M15 cells induced by IPTG. The protein was purified with a nickel HiTrap chelating metal affinity column. Results The recombinant expression plasmid was successfully constructed and the protein was well expressed in E. coli strain M15 cells. The ideal pure protein was obtained by purification. Western blott