WorldWideScience

Sample records for acid-binding immunoglobulin-like lectin-6

  1. Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells

    Sabrina Gruber

    2016-03-01

    Full Text Available Atherosclerosis is initiated and sustained by hypercholesterolemia, which results in the generation of oxidized LDL (OxLDL and other metabolic byproducts that trigger inflammation. Specific immune responses have been shown to modulate the inflammatory response during atherogenesis. The sialic acid-binding immunoglobulin-like lectin G (Siglec-G is a negative regulator of the functions of several immune cells, including myeloid cells and B-1 cells. Here, we show that deficiency of Siglec-G in atherosclerosis-prone mice inhibits plaque formation and diet-induced hepatic inflammation. We further demonstrate that selective deficiency of Siglec-G in B cells alone is sufficient to mediate these effects. Levels of B-1 cell-derived natural IgM with specificity for OxLDL were significantly increased in the plasma and peritoneal cavity of Siglec-G-deficient mice. Consistent with the neutralizing functions of OxLDL-specific IgM, Siglec-G-deficient mice were protected from OxLDL-induced sterile inflammation. Thus, Siglec-G promotes atherosclerosis and hepatic inflammation by suppressing protective anti-inflammatory effector functions of B cells.

  2. The expression of sialic acid-binding immunoglobulin-like lectin 1 on peripheral mononuclear cells in patients with coronary heart disease and its clinical significance%唾液酸结合免疫球蛋白样凝集素1在冠状动脉粥样硬化性心脏病患者外周血单个核细胞的表达及临床意义

    熊怡淞; 荣光华; 仲人前; 周运恒; 吴炜霖; 张玲珍; 梁艳; 杨再兴; 耿红莲; 王皓; 王爱华

    2009-01-01

    目的 观察唾液酸结合免疫球蛋白样凝集素1(sialic acid-binding immunoglobulin-likelectin 1,Siglec-1,也称CD169)在冠状动脉粥样硬化性心脏病(CHD)患者外周血淋巴细胞、单核细胞和中性粒细胞上的表达水平,并探讨其与冠状动脉粥样硬化发生发展的关系.方法 流式细胞术检测57例CHD患者及38名健康对照者外周血CD14CD169双阳性细胞的表达率;生化常规测定所有入选者血脂水平;实时荧光相对定量逆转录(FQ-RT)-PCR方法检测入选对象外周血单个核细胞(PBMCs)中CD169 mRNA的含量.结果 流式细胞仪检测发现,CD169在健康对照组及CHD组淋巴细胞和中性粒细胞上均无表达;CHD组单核细胞CD14CD169双阳性率为(12.7±2.4)%,显著高于健康对照组[(1.0±0.3)%,t=23.2,P0.05]和mRNA平均拷贝数(分别为健康对照组的3.64和2.79倍,t=0.98,P>0.05)差异均无统计学意义.结论 CD169组成性表达于特定组织巨噬细胞上,健康人外周血单核细胞上并不表达,单核巨噬细胞受到炎症刺激时,CD169表达迅速上调.CD169蛋白及mRNA含量在CHD患者外周血单核细胞上表达显著升高,CHD患者外周血单核细胞已发生巨噬细胞化,单核巨噬细胞介导的免疫炎症反应在CHD发生发展过程中起重要作用.%Objective To investigate the expression of sialic acid-binding immunoglobulin-like lectin-one (Siglec-1, also called CD169) in lymphocytes, monocytes and neutrophils in peripheral blood in patients with coronary heart disease(CHD), and explore the relationship between Siglec-1 expression and atheresclerosis. Methods CD145 CD169 positive cell proportion and CD169 mRNA levels were respectively measured by flow cytometry and real-time quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) in 57 CHD patients and 38 healthy controls. And the levels of serum hpids were determined by automatic biochemistry analyzer. Results The flow cytometry analysis showed that CD169

  3. 类风湿关节炎患者外周血单个核细胞唾液酸结合免疫球蛋白样凝集素-1的表达及与疾病活动度的关系%The expression of sialic acid-binding immunoglobulin-like lectin-1 on peripheral blood mononuclear cells and its relationship with disease activity in rheumatoid arthritis

    熊怡淞; 程悦; 吴艾霖; 王艳艳; 熊杰; 仲人前

    2013-01-01

    目的 观察唾液酸结合免疫球蛋白样凝集素-1 (Siglec-1)在类风湿关节炎(RA)患者外周血单个核细胞(PBMCs)上的表达水平,并探讨其与RA疾病活动度的关系.方法 分别采用流式细胞术及实时荧光定量反转录聚合酶链反应(RT-PCR)检测42例RA患者、28例骨关节炎患者和26名健康对照者外周血Siglec-1蛋白和mRNA表达,并将Siglec-1表达与28个关节疾病活动度评分(DAS28)以及超敏C反应蛋白(hs-CRP)作相关性分析.组间均数比较采用t检验,相关性分析采用Pearson相关分析.结果 流式细胞仪检测发现,RA组Siglec-1阳性细胞占PBMCs比例为(15.2±7.6)%,明显高于骨关节炎组[(2.3±2.6)%]和健康对照组[(2.1±1.6)%,t值分别为8.615,8.661;P均<0.01],并且表达Siglec-1的细胞主要为单核细胞;RA组Siglec-1 mRNA的相对表达量为(3.4±1.5),明显高于骨关节炎组(1.2±0.4)和健康对照组(1.0±0.4)(t值分别为3.446,3.966;P均<0.05).而骨关节炎组和健康对照组之间Siglec-1蛋白和mRNA表达差异无统计学意义(P>0.05).此外,RA患者Siglec-1的表达与DAS28及hs-CRP均呈正相关(r值分别为0.89,0.48;P均<0.01).结论 RA患者外周血PBMCs已经激活并高表达Siglec-1,Siglec-1可能作为无创性指标用于监测RA疾病活动度和炎症程度.%Objective To investigate the expression of sialic acid-binding immunoglobulin-like lectin-1 (Siglec-1) in the peripheral blood mononuclear cells (PBMCs) in patients with rheumatoid arthritis (RA),osteoarthritis (OA) and healthy controls and to explore the relationship between Siglec-1 expression and disease activity in RA.Methods Siglec-1 protein and mRNA levels were measured by flow cytometry and real-time quantitative reversetranscription-polymerase chain reaction (qRT-PCR) in 42 RA patients,28 OA patients and 26 healthy controls,respectively.The correlation studies between Siglec-1 and disease activity score 28 (DAS28) or C-reactive protein were

  4. Associations of Killer Cell Immunoglobulin-Like Receptor Genes with Rheumatoid Arthritis

    S. Ramírez-De los Santos

    2012-01-01

    Full Text Available Objective: Rheumatoid Arthritis (RA is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28null T-cells, both present in synovial membrane of RA. Therefore we evaluated the associations of KIR genes with RA.

  5. Evolutionarily conserved paired immunoglobulin-like receptor α (PILRα) domain mediates its interaction with diverse sialylated ligands.

    Sun, Yonglian; Senger, Kate; Baginski, Tomasz K; Mazloom, Anita; Chinn, Yvonne; Pantua, Homer; Hamidzadeh, Kajal; Ramani, Sree Ranjani; Luis, Elizabeth; Tom, Irene; Sebrell, Andrew; Quinones, Gabriel; Ma, Yan; Mukhyala, Kiran; Sai, Tao; Ding, Jiabing; Haley, Benjamin; Shadnia, Hooman; Kapadia, Sharookh B; Gonzalez, Lino C; Hass, Philip E; Zarrin, Ali A

    2012-05-04

    Paired immunoglobulin-like receptor (PILR) α is an inhibitory receptor that recognizes several ligands, including mouse CD99, PILR-associating neural protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s) of interactions between PILRα and its cellular ligands are not well understood, as are the molecular determinants of PILRα/ligand interactions. To address these uncertainties, we sought to identify additional PILRα ligands and further define the molecular basis for PILRα/ligand interactions. Here, we identify two novel PILRα binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRα ligands, and on known PILRα ligands, are compulsory for PILRα binding. Sialylation-dependent ligand recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig-like lectins. SIGLEC1 Ig domain shares ∼22% sequence identity with PILRα, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRα and position 126 in human PILRα. We observe that PILRα/ligand interactions require conserved PILRα Arg-133 (mouse) and Arg-126 (human), in correspondence with a previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand interactions. Homology modeling identifies striking similarities between PILRα and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRα recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRα is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRα ligands are expressed.

  6. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  7. The association of killer cell immunoglobulin like receptor gene polylmorphism with cytomegalovirus infection after hematopoietic stem cell transplantation

    吴小津

    2013-01-01

    Objective To explore the influence of the killer cell immunoglobulin like receptor(KIR)gene polymorphism on cytomegalovirus(CMV)infection and pathogenesis after hematopoietic stem cell transplantation(HSCT)

  8. The leukocyte immunoglobulin-like receptors (LIRs): a new family of immune regulators.

    Fanger, N A; Borges, L; Cosman, D

    1999-08-01

    Identification of a counterstructure for the human cytomegalovirus-encoded major histocompatibility complex class I-related gene product, UL18, has led to the discovery of a novel family of immunoreceptors, termed leukocyte immunoglobulin-like receptors (LIRs). The LIRs are differentially expressed in cells of the dendritic cell, monocytic and lymphocytic lineages, and appear to mediate diverse roles in immune regulation. This review summarizes the expression, distribution, and signaling capacities of the LIRs and discusses possible roles of the LIRs in both inhibition and activation of the cellular responses.

  9. Identification of the ancestral killer immunoglobulin-like receptor gene in primates

    Coggill Penny

    2006-08-01

    Full Text Available Abstract Background Killer Immunoglobulin-like Receptors (KIR are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. Results Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0 in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens, common chimpanzee (Pan troglodytes, gorilla (Gorilla gorilla, rhesus monkey (Macaca mulatta and common marmoset (Callithrix jacchus. We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells. Conclusion One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution.

  10. Expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1 on osteoclasts and its potential role in rheumatoid arthritis

    Yuan Zhang

    2013-04-01

    Full Text Available OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis. METHODS: In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay. RESULTS: We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis. CONCLUSION: Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis.

  11. Role of Killer Immunoglobulin-Like Receptor and Ligand Matching in Donor Selection

    Meral Beksaç

    2012-01-01

    Full Text Available Despite all efforts to improve HLA typing and immunosuppression, it is still impossible to prevent severe graft versus host disease (GVHD which can be fatal. GVHD is not always associated with graft versus malignancy and can prevent stem cell transplantation from reaching its goals. Overall T-cell alloreactivity is not the sole mechanism modulating the immune defense. Innate immune system has its own antigens, ligands, and mediators. The bridge between HLA and natural killer (NK cell-mediated reactions is becoming better understood in the context of stem cell transplantation. Killer immunoglobulin-like receptors (KIRs constitute a wide range of alleles/antigens segregated independently from the HLA alleles and classified into two major haplotypes which imprints the person's ability to suppress or to amplify T-cell alloreactivity. This paper will summarize the impact of both activating and inhibitory KIRs and their ligands on stem cell transplantation outcome. The ultimate goal is to develop algorithms based on KIR profiles to select donors with maximum antileukemic and minimum antihost effects.

  12. Killer immunoglobulin-like receptor (KIR and HLA genotypes affect the outcome of allogeneic kidney transplantation.

    Izabela Nowak

    Full Text Available BACKGROUND: Recipient NK cells may detect the lack of recipient's (i.e., self HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs. KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.

  13. Association of Killer Cell Immunoglobulin- Like Receptor Genes in Iranian Patients with Rheumatoid Arthritis.

    Masoumeh Nazari

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disorder characterized by persistent synovitis, ultimately leading to cartilage and bone degeneration. Natural Killer cells and CD28 null T-cells are suspected as role players in RA pathogenesis. These cells are similar in feature and function, as they both exert their cytotoxic effect via Killer Cell Immunoglobulin- Like Receptors (KIR on their surface. KIR genes have either an inhibitory or activating effect depending on their intracytoplasmic structure. Herein we genotyped 16 KIR genes, 3 pseudo genes and 6 HLA class І genes as their corresponding ligands in RA patients and control subjects.In this case-control study, KIR and HLA genes were genotyped in 400 RA patients and 372 matched healthy controls using sequence-specific primers (SSP-PCR. Differences in the frequency of genes and haplotypes were determined by χ² test.KIR2DL2, 2DL5a, 2DL5b and activating KIR: KIR2DS5 and 3DS1 were all protective against RA. KIR2DL5 removal from a full Inhibitory KIR haplotype converted the mild protection (OR = 0.56 to a powerful predisposition to RA (OR = 16.47. Inhibitory haplotype No. 7 comprising KIR2DL5 in the absence of KIR2DL1 and KIR2DL3 confers a 14-fold protective effect against RA.Individuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.

  14. Impact of killer immunoglobulin-like receptor-human leukocyte antigens ligand incompatibility among renal transplantation.

    Alam, S; Rangaswamy, D; Prakash, S; Sharma, R K; Khan, M I; Sonawane, A; Agrawal, S

    2015-01-01

    Killer immunoglobulin-like receptor (KIR) gene shows a high degree of polymorphism. Natural killer cell receptor gets activated once they bind to self-human leukocyte antigens (HLAs) with specific ligand. KIR gene and HLA ligand incompatibility due to the presence/absence of KIR in the recipient and the corresponding HLA ligand in the allograft may impact graft survival in solid organ transplantation. This study evaluates the effect of matches between KIR genes and known HLA ligands. KIR genotypes were determined using sequence specific primer polymerase chain reaction. Presence of certain KIR in a recipient, where the donor lacked the corresponding HLA ligand was considered a mismatch. The allograft was considered matched when both KIR receptor and HLA alloantigen reveald compatibility among recipient and donor. The data revealed better survival among individuals with matched inhibitory KIR receptors and their corresponding HLA ligands (KIR2DL2/DL3-HLAC2, KIR3DL1-HLABw4). On the contrary, no adverse effect was seen for matched activating KIR receptors and their corresponding HLA ligands. One of the activating gene KIR2DS4 showed risk (P = 0.0413, odds ratio = 1.91, 95% confidence interval = 1.02-3.57) association with renal allograft rejection. We conclude that the presence of inhibitory KIR gene leads to better survival; whereas activating motifs show no significant role in renal allograft survival.

  15. Increased leucine-rich repeats and immunoglobulin- like domains 1 expression enhances chemosensitivity in glioma

    Baohui Liu; Shenqi Zhang; Dong Ruan; Xiaonan Zhu; Zhentao Guo; Huimin Dong; Mingmin Yan; Qianxue Chen; Daofeng Tian; Liquan Wu; Junmin Wang; Qiang Cai; Heng Shen; Baowei Ji; Long Wang

    2011-01-01

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is an anti-oncogene.LRIG1 is correlated with Bcl-2 in ependymomas.Decreased Bcl-2 and manganese superoxide dismutase expression can improve the chemosensitivity of glioma.In the present study, a tissue microarray of human brain astrocytomas was constructed.To investigate the relationship of LRIG1 with Bcl-2 and manganese superoxide dismutase, LRIG1, Bcl-2 and manganese superoxide dismutase expression in our tissue microarray was determined using immunohistochemistry.In addition, we constructed the LRIG1-U251 cell line, and its responses to doxorubicin and temozolomide were detected using the MTT assay.Results showed that LRIG1 expression was significantly negatively correlated with Bcl-2 and manganese superoxide dismutase expression in glioma.Also, proliferation of LRIG1-U251 cells exposed to doxorubicin or temozolomide was significantly inhibited, i.e.in the LRIG1-U251 cell line, the chemosensitivity to doxorubicin and temozolomide was increased.This indicates that increased LRIG1 expression produces a chemosensitivity in glioma.

  16. Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques

    Parham Peter

    2011-06-01

    Full Text Available Abstract Background Human killer immunoglobulin-like receptors (KIRs play a critical role in governing the immune response to neoplastic and infectious disease. Rhesus macaques serve as important animal models for many human diseases in which KIRs are implicated; however, the study of KIR activity in this model is hindered by incomplete characterization of KIR genetics. Results Here we present a characterization of KIR genetics in rhesus macaques (Macaca mulatta. We conducted a survey of KIRs in this species, identifying 47 novel full-length KIR sequences. Using this expanded sequence library to build upon previous work, we present evidence supporting the existence of 22 Mamu-KIR genes, providing a framework within which to describe macaque KIRs. We also developed a novel pyrosequencing-based technique for KIR genotyping. This method provides both comprehensive KIR genotype and frequency estimates of transcript level, with implications for the study of KIRs in all species. Conclusions The results of this study significantly improve our understanding of macaque KIR genetic organization and diversity, with implications for the study of many human diseases that use macaques as a model. The ability to obtain comprehensive KIR genotypes is of basic importance for the study of KIRs, and can easily be adapted to other species. Together these findings both advance the field of macaque KIRs and facilitate future research into the role of KIRs in human disease.

  17. Axon regeneration impediment:the role of paired immunoglobulin-like receptor B

    Jing Liu; Yan Wang; Wei Fu

    2015-01-01

    Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to the Nogo receptor (NgR), the paired immunoglobulin-like receptor B (PirB) is a recently discovered coreceptor of Nogo, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein. Concurrent blocking of NgR and PirB almost completely elim-inates the inhibitory effect of myelin-associated inhibitory molecules on axonal regeneration. PirB participates in a key pathological process of the nervous system, speciifcally axonal regener-ation inhibition. PirB is an inhibitory receptor similar to NgR, but their effects are not identical. This study summarizes the structure, distribution, relationship with common nervous system diseases, and known mechanisms of PirB, and concludes that PirB is also distributed in cells of the immune and hematopoietic systems. Further investigations are needed to determine if im-munomodulation and blood cell migration involve inhibition of axonal regeneration.

  18. Killer immunoglobulin-like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease.

    López-Hernández, Ruth; Campillo, Jose A; Legaz, Isabel; Valdés, Mariano; Salama, Hortensia; Boix, Francisco; Hernández-Martínez, A M; Eguia, Jorge; González-Martínez, G; Moya-Quiles, Maria R; Minguela, Alfredo; García-Alonso, Ana; Carballo, Fernando; Muro, Manuel

    2016-11-01

    Immunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR-sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.

  19. Association of Killer Cell Immunoglobulin-Like Receptor Genes with Hodgkin's Lymphoma in a Familial Study

    Williams, Fionnuala; Orsi, Laurent; Amiel, Corinne; Lependeven, Catherine; Antoni, Guillemette; Hermine, Olivier; Brice, Pauline; Ferme, Christophe; Carde, Patrice; Canioni, Danielle; Brière, Josette; Raphael, Martine; Nicolas, Jean-Claude; Clavel, Jacqueline; Middleton, Derek; Vivier, Eric; Abel, Laurent

    2007-01-01

    Background Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. Methodology We included 90 families with 90 HL index cases (age 16–35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. Principal Findings Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23–0.85] and 0.42[0.21–0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18–71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. Conclusions This work defines a template for family-based association studies based on full genotypic

  20. Association of killer cell immunoglobulin-like receptor genes with Hodgkin's lymphoma in a familial study.

    Caroline Besson

    Full Text Available BACKGROUND: Epstein-Barr virus (EBV is the major environmental factor associated with Hodgkin's lymphoma (HL, a common lymphoma in young adults. Natural killer (NK cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs, which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. METHODOLOGY: We included 90 families with 90 HL index cases (age 16-35 years and 255 first-degree relatives (parents and siblings. We developed a procedure for reconstructing full genotypic information (number of gene copies at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. PRINCIPAL FINDINGS: Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23-0.85] and 0.42[0.21-0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18-71 years. In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. CONCLUSIONS: This work defines a template for family-based association studies based on full

  1. Distribution of the killer cell immunoglobulin-like receptors in Mexican Mestizos.

    Contreras, G; Aláez, C; Murguía, A; García, D; Flores, H; Gorodezky, C

    2007-04-01

    Understanding the complex interaction between human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) requires study of both HLA and KIR diversity in the same population. The presence of KIR genes 2DL1, 2, 3, 4, 5, KIR3DL1, 3DL2, 3DL3, KIR2DS1, 2DS2, 2DS3, 2DS4, 2DS5, KIR3DS1, KIR3DP1, KIR2DP1 was determined in 54 unrelated Mexican Mestizo donors. The PCR sequence-specific oligonucleotide probe One Lambda kit (Luminex) kindly given by J. Lee was used for typing. The software analyses the combination obtained for each of the five exons. Five controls (UCLA DNA exchange) were run as quality control. The gene frequency (GF) was calculated for the 16 KIR loci; the GF of individual genes was 100% for 2DL4, 3DL1, 3DL2, 3DL3, 3DP1. KIR2DL1 (76.43%), KIR2DL2 (37.64%), KIR2DL3 (76.43%), KIR2DL5 (29.29%), KIR3DS1 (23.02%), KIR2DS1 (21.83%), KIR2DS2 (37.64%), KIR2DS3 (50.93%), KIR2DS4 (86.93%), KIR2DS5 (29.29%), KIR2DP1 (86.39%). We observed similar frequencies with Caucasians and Mediterraneans, with exceptions: KIR3DL1 which was present in 100% Mexicans, ranged from 62% to 75% in Caucasians; 2DS3 (50.9%) vs 14-20% 2DS4 (86.39%) vs 65-79% and 2DS5 (29.29%) vs 11-18% in Caucasians. The finding of 23 phenotypes in 54 individuals accounting for both chromosomes, demonstrates the enormous diversity. We found 14 different combinations of stimulatory KIRs in the phenotypes; every subject had at least one stimulatory KIR; in all of them, 2DS4 existed except for one person who may have some new combination: 2DS2 2DS3. Extended family data will offer accurate and precise haplotypes to provide an insight on the significance of ethnic distribution and KIR repertoire.

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

    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...

  3. Killer cell immunoglobulin-like receptor gene associations with autoimmune and allergic diseases, recurrent spontaneous abortion, and neoplasms

    Piotr eKusnierczyk

    2013-01-01

    Full Text Available Killer cell immunoglobulin-like receptors (KIRs are a family of cell surface inhibitory or activating receptors expressed on natural killer cells and some subpopulations of T lymphocytes. KIR genes are clustered in the 19q13.4 region and are characterized by both allelic (high numbers of variants and haplotypic (different numbers of genes for inhibitory and activating receptors on individual chromosomes polymorphism. This contributes to diverse susceptibility to diseases and other clinical situations. Associations of KIR genes, as well as of genes for their ligands, with selected diseases such as psoriasis vulgaris and atopic dermatitis, rheumatoid arthritis, recurrent spontaneous abortion, and non-small cell lung cancer are discussed in the context of NK and T cell functions.

  4. Engineering a Lys-Asn isopeptide bond into an immunoglobulin-like protein domain enhances its stability

    Kwon, Hanna; Young, Paul G.; Squire, Christopher J.; Baker, Edward N.

    2017-01-01

    The overall stability of globular protein structures is marginal, a balance between large numbers of stabilizing non-covalent interactions and a destabilizing entropic term. Higher stability can be engineered by introduction of disulfide bonds, provided the redox environment is controlled. The discovery of stabilizing isopeptide bond crosslinks, formed spontaneously between lysine and asparagine (or aspartic acid) side chains in certain bacterial cell-surface proteins suggests that such bonds could be introduced by protein engineering as an alternative protein stabilization strategy. We report the first example of an isopeptide bond engineered de novo into an immunoglobulin-like protein, the minor pilin FctB from Streptococcus pyogenes. Four mutations were sufficient; lysine, asparagine and glutamic acid residues were introduced for the bond-forming reaction, with a fourth Val/Phe mutation to help steer the lysine side chain into position. The spontaneously-formed isopeptide bond was confirmed by mass spectrometry and X-ray crystallography, and was shown to increase the thermal stability by 10 °C compared with the wild type protein. This novel method for increasing the stability of IgG-like proteins has potential to be adopted by the field of antibody engineering, which share similar β-clasp Ig-type domains. PMID:28202898

  5. Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with epithelial ovarian cancer.

    Giebel, Sebastian; Boratyn-Nowicka, Agnieszka; Karabon, Lidia; Jedynak, Anna; Pamula-Pilat, Jolanta; Tecza, Karolina; Kula, Dorota; Kowal, Monika; Frydecka, Irena; Grzybowska, Ewa

    2014-06-01

    Killer immunoglobulin-like receptors (KIRs) regulate function of NK cells and subsets of T cells. HLA class I molecules are ligands for inhibitory KIRs while specificity of activating KIRs is mainly unknown. Both KIR and HLA genotypes are highly polymorphic. In this study we analyzed associations of KIR and KIR ligand genes with the incidence and clinical course of epithelial ovarian cancer. DNA of 142 patients was analyzed for KIR genes and 103 samples were typed for HLA class I. Control group consisted of 200 healthy individuals, including 83 women, analyzed separately. The frequency of KIR genes in patients and controls were comparable. HLA-C group 1 (ligand for KIR2DL2/3) was more frequent in patients than in controls (86.4% vs. 67.5%, p=0.002). The frequency of KIR2DS4fl was higher in patients with endometrioid cancer (72.3%) compared with other histological subtypes (36.5%, p=0.004) and controls (29.5%, p=0.0001). KIR and KIR ligand genotype did not influence significantly the clinical course of the disease. We conclude that the genotype of KIR ligands is strongly associated with the incidence of epithelial ovarian cancer while KIR2DS4fl confers susceptibility to endometrioid subtype of the disease.

  6. In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy.

    Shatunov, Alexey; Olivé, Montse; Odgerel, Zagaa; Stadelmann-Nessler, Christine; Irlbacher, Kerstin; van Landeghem, Frank; Bayarsaikhan, Munkhuu; Lee, Hee-Suk; Goudeau, Bertrand; Chinnery, Patrick F; Straub, Volker; Hilton-Jones, David; Damian, Maxwell S; Kaminska, Anna; Vicart, Patrick; Bushby, Kate; Dalakas, Marinos C; Sambuughin, Nyamkhishig; Ferrer, Isidro; Goebel, Hans H; Goldfarb, Lev G

    2009-05-01

    Myofibrillar myopathies (MFMs) are an expanding and increasingly recognized group of neuromuscular disorders caused by mutations in DES, CRYAB, MYOT, and ZASP. The latest gene to be associated with MFM was FLNC; a p.W2710X mutation in the 24th immunoglobulin-like repeat of filamin C was shown to be the cause of a distinct type of MFM in several German families. We studied an International cohort of 46 patients from 39 families with clinically and myopathologically confirmed MFM, in which DES, CRYAB, MYOT, and ZASP mutations have been excluded. In patients from an unrelated family a 12-nucleotide deletion (c.2997_3008del) in FLNC resulting in a predicted in-frame four-residue deletion (p.Val930_Thr933del) in the seventh repeat of filamin C was identified. Both affected family members, mother and daughter, but not unrelated control individuals, carried the p.Val930_Thr933del mutation. The mutation is transcribed and, based on myopathological features and immunoblot analysis, it leads to an accumulation of dysfunctional filamin C in the myocytes. The study results suggest that the novel p.Val930_Thr933del mutation in filamin C is the cause of MFM but also indicate that filamin C mutations are a comparatively rare cause of MFM.

  7. Paternal HLA-C and Maternal Killer-Cell Immunoglobulin-Like Receptor Genotypes in the Development of Autism

    Gamliel, Moriya; Anderson, Karen L.; Ebstein, Richard P.; Yirmiya, Nurit; Mankuta, David

    2016-01-01

    Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal–fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents. This study enrolled 49 ASD children from different Israeli families, and their healthy parents. Among the parents, a higher frequency of HLA-C2 allotypes was found in the fathers, while its corresponding ligand 2DS1 was found in higher percentage in the maternal group. However, such skewing in KIR:HLA frequencies did not appear in the ASD children. Additionally, analysis of “overall activation” indicated higher activation in maternal than in paternal cohorts. PMID:27517034

  8. Structural and functional analysis of slit and heparin binding to immunoglobulin-like domains 1 and 2 of Drosophila Robo.

    Fukuhara, Noémi; Howitt, Jason A; Hussain, Sadaf-Ahmahni; Hohenester, Erhard

    2008-06-06

    Recognition of the secreted protein Slit by transmembrane receptors of the Robo family provides important signals in the development of the nervous system and other organs, as well as in tumor metastasis and angiogenesis. Heparan sulfate (HS) proteoglycans serve as essential co-receptors in Slit-Robo signaling. Previous studies have shown that the second leucinerich repeat domain of Slit, D2, binds to the N-terminal immunoglobulin-like domains of Robo, IG1-2. Here we present two crystal structures of Drosophila Robo IG1-2, one of which contains a bound heparin-derived oligosaccharide. Using structure-based mutagenesis of a Robo IG1-5 construct we identified key Slit binding residues (Thr-74, Phe-114, Arg-117) forming a conserved patch on the surface of IG1; mutation of similarly conserved residues in IG2 had no effect on Slit binding. Mutation of conserved basic residues in IG1 (Lys-69, Arg-117, Lys-122, Lys-123), but not in IG2, reduced binding of Robo IG1-5 to heparin, in full agreement with the Robo-heparin co-crystal structure. Our collective results, together with a recent crystal structure of a minimal human Slit-Robo complex ( Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., Cusack, S., and McCarthy, A. A. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 14923-14928 ), reveal a contiguous HS/heparin binding surface extending across the Slit-Robo interface. Based on the size of this composite binding site, we predict that at least five HS disaccharide units are required to support Slit-Robo signaling.

  9. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism.

    Torres, Anthony R; Westover, Jonna B; Gibbons, Cole; Johnson, Randall C; Ward, David C

    2012-10-01

    Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p = 0.00003 [Odds ratio = 2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism.

  10. Diversity of killer cell immunoglobulin-like receptor genes in Indonesian populations of Sumatra, Sulawesi and Moluccas Islands.

    Velickovic, M; Velickovic, Z; Panigoro, R; Dunckley, H

    2010-10-01

    Killer immunoglobulin-like receptors (KIRs) regulate the activity of natural killer and T cells through interaction with specific human leukocyte antigen (HLA) molecules on target cells. Like HLA class I genes that are characterised by extreme allelic polymorphism, KIR genes are diverse and vary in both gene content and allelic polymorphism. Population studies conducted over the last several years have showed that KIR gene frequencies (GF) and genotype content vary among different ethnic groups, indicating the extent of KIR diversity. Some studies have also shown the effect of the presence or absence of specific KIR genes in human disease. We have recently reported the distribution of KIR genes in populations from Java (Central Javanese and the Sundanese of West Java), East Timor (Timorese), Kalimantan provinces of Indonesian Borneo (Dayaks) and Irian Jaya (Western half of the island of New Guinea; Melanese). We here extend analysis of the KIR genes in populations from North Sulawesi (Minahasans), West Sumatra (Minangs) and Moluccas Islands. All 16 KIR genes were observed in all three populations. Variation in GF between populations was observed, except for the KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 genes, which were present in every individual tested. When comparing KIR GF between populations, both principal component analysis and phylogenetic tree analyses showed a close relationship between Minahasan and Moluccan populations that are clustered with Timorese in the same clade. The Minang tribe lies between the Javanese/Kalimantan and the Timorese/Minahasan/Moluccan clades, whereas Irianese show the greatest genetic distances from other Indonesian populations. The results correspond well with the history of migration in Indonesia and will contribute to the understanding of the genetic as well as the geographic history of the region.

  11. Killer cell immunoglobulin-like receptor genes in Latvian patients with type 1 diabetes mellitus and healthy controls.

    Nikitina-Zake, Liene; Rajalingham, Raja; Rumba, Ingrida; Sanjeevi, Carani B

    2004-12-01

    T1DM is very common in Sweden and is positively associated with HLA class II genes. Approximately 89% of the newly diagnosed patients carry the high-risk HLA DR4-DQ8 and DR3-DQ2. The remaining 11% develop T1DM without them. This can be due to involvement of other genes and environmental factors. Natural killer (NK) cells of the innate immune system are important in antiviral and antitumor immunity. They are implicated in the etiology of autoimmune T1DM. Human NK cells express killer cell immunoglobulin-like receptors (KIR) that belong to the polymorphic multigene family in chromosome 19q3.4. They modulate NK cell response by interacting with HLA class I. In addition, polymorphic MICA in HLA class I interacts with non-polymorphic NKG2D receptor on NK cells. We have studied, in addition to HLA-DR and -DQ, genes of the innate immune system MICA and KIR in Latvian patients (n = 98) with T1DM and controls (n = 100). They were genotyped using standard PCR-based typing methods. MICA allele 5 is positively associated with T1DM. KIR2DL2 and KIR2DS2 were both positively associated. Combined association of MICA4 and KIR2DL2 gave an odds ration (OR) of 26.7. However, the combined risk of KIR2DL2 and HLA class II genes, HLADR3 (OR = 73.4), DR4 (OR = 66.8), and DR3 and DR4 (OR = 88.3), was higher. The maximum risk was when KIR2DL2, MICA5, and DR3/DR4 were in combination. In conclusion, our results suggest that a balance between innate and acquired immunity is important, and an imbalance coud lead to T1DM.

  12. Association between killer cell immunoglobulin-like receptor (KIR) polymorphisms and systemic lupus erythematosus (SLE) in populations

    Liang, Hui-ling; Ma, Shu-juan; Tan, Hong-zhuan

    2017-01-01

    Abstract Background: Recently, a growing number of studies show that the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms may play a role in the systemic lupus erythematosus (SLE) susceptibility. Nonetheless, the results were inconsistent. Thus, a meta-analysis was carried out by integrating multiple research to clarify the association between KIR polymorphisms and SLE susceptibility. Methods: The Web of Science, Embase (Ovid), PubMed, Elsevier Science Direct, the Chinese Biomedical Database and CNKI, Wanfang databases (last search was updated on May 15, 2016) were systematically searched to select studies on addressing the association between the KIR polymorphisms and susceptibility to SLE in populations. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated. Results: A total of 10 published case-control studies involving 1450 SLE patients and 1758 controls were available for this meta-analysis. Results suggested that KIR2DL1 might be a risk factor for SLE (OR 2DL1 =1.047, 95% CI=1.011–1.083) in all subjects. The KIR2DL3, KIR2DL5 were identified as protective factors for SLE in Asian populations (OR2DL3= 0.215, 95% CI = 0.077–0.598; OR2DL5 = 0.588, 95% CI = 0.393–0.881), but not in Caucasians. Conclusions: The meta-analysis results suggested that 2DL1 might be a potential risk factor and 2DL3, 2DL5 might be protective factors for SLE in Asians but not in Caucasians. PMID:28272205

  13. Echinococcus granulosus fatty acid binding proteins subcellular localization.

    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.

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

    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.

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

    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.

  16. Expression and sub-cellular localization of leucine-rich repeats and immunoglobulin-like domains are related to antioxidant enzymes in human ependymoma and oligodendroglioma

    Wei Yi; Lin Liu; Okechi Humphrey; Qianxue Chen; Shulan Huang

    2011-01-01

    The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 (LRIG1) and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.

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

    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.

  18. The clinical significance of fatty acid binding proteins

    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.

  19. Human NK cells maintain licensing status and are subject to killer immunoglobulin-like receptor (KIR) and KIR-ligand inhibition following ex vivo expansion.

    Wang, Wei; Erbe, Amy K; Alderson, Kory A; Phillips, Emily; Gallenberger, Mikayla; Gan, Jacek; Campana, Dario; Hank, Jacquelyn A; Sondel, Paul M

    2016-09-01

    Infusion of allogeneic NK cells is a potential immunotherapy for both hematopoietic malignancies and solid tumors. Interactions between killer immunoglobulin-like receptors (KIR) on human NK cells and KIR-ligands on tumor cells influence the magnitude of NK function. To obtain sufficient numbers of activated NK cells for infusion, one potent method uses cells from the K562 human erythroleukemia line that have been transfected to express activating 41BB ligand (41BBL) and membrane-bound interleukin 15 (mbIL15). The functional importance of KIRs on ex vivo expanded NK cells has not been studied in detail. We found that after a 12-day co-culture with K562-mbIL15-41BBL cells, expanded NK cells maintained inhibition specificity and prior in vivo licensing status determined by KIR/KIR-ligand interactions. Addition of an anti-CD20 antibody (rituximab) induced NK-mediated antibody-dependent cellular cytotoxicity and augmented killing of CD20+ target cells. However, partial inhibition induced by KIR/KIR-ligand interactions persisted. Finally, we found that extended co-cultures of NK cells with stimulatory cells transduced to express various KIR-ligands modified both the inhibitory and activating KIR repertoires of the expanded NK cell product. These studies demonstrate that the licensing interactions known to occur during NK ontogeny also influence NK cell function following NK expansion ex vivo with HLA-null stimulatory cells.

  20. No Correlation Exists between Disease Activity and the Expression of Killer-Cell Immunoglobulin-Like Receptors in Patients with Rheumatoid Arthritis

    Toshiaki Kogure

    2007-01-01

    Full Text Available Objective. The genes for killer-cell immunoglobulin-like receptors (KIRs have been cloned and their functions and expression in patients with rheumatoid arthritis (RA have been partially clarified. However, the correlation between their expression and disease activity has not been analyzed in patients with RA. Thus, we measured KIR expression on lymphocytes in patients with RA, and assessed the correlation between KIR expression and disease activity. Patients and Methods. In the cross-sectional study, 15 patients (9 females and 6 males who fulfilled the diagnostic criteria for RA were assessed. In the longitudinal study, patients who were followed-up for 3 months were assessed. CD158a/b expression on peripheral blood mononuclear cells (PBMC of RA patients was analyzed using flow cytometry. Results. No significant correlation between KIR expression and CRP, ESR, or IgM-RF was observed. There was no remarkable change in the expression of KIRs between the baseline and after 3 months. Additionally, in the 5 patients whose expression of KIRs particularly changed, the time-related changes in the expression of KIRs were independent from those of inflammation parameters and IgM-RF. Conclusion. There was no correlation between KIR expression and disease activity; therefore, the clinical use of KIR expression should be limited, while unnatural KIR expression may be involved in the pathogenesis of RA, but not a recruitment of chronic inflammation to induce joint damage.

  1. Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains fusion in fishes and ray-finned fishes specific intron insertion after separation from zebrafish.

    Kumar, Abhishek; Bhandari, Anita; Sarde, Sandeep J; Goswami, Chandan

    2014-07-18

    C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1'. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ∼450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys.

  2. Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration dififculties after unilateral lumbar spinal cord injury

    Wan-shu Peng; Chao Qi; Hong Zhang; Mei-ling Gao; Hong Wang; Fei Ren; Xia-qing Li

    2015-01-01

    Paired immunoglobulin-like receptor B (PirB) is a functional receptor of myelin-associated in-hibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of PirB on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of PirB (via immunolfuorescence) in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for PirB increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, PirB was mainly distributed along neuronal and axonal membranes. PirB was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunore-activity for PirB was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the ifndings suggest a pattern of PirB immunoreactivity in the nervous system after uni-lateral spinal transection injury, and also indicate that PirB may suppress repair after injury.

  3. Identification of paired immunoglobulin-like type 2 receptor α as hepatitis B virus DNA polymerase transactivated protein 1 interacting proteins.

    Lun, Yong-Zhi; Chi, Qing; Wang, Xue-Lei; Wang, Fang; Sui, Wen

    2014-02-01

    Hepatitis B Virus (HBV) DNA polymerase transactivated protein 1 (HBVDNAPTP1) is a novel protein transfected by HBV DNA polymerase, which has been screened by a suppression subtractive hybridization technique. In the present study, a yeast two-hybrid system was used to screen the proteins interacting with HBVDNAPTP1 in leukocytes in order to investigate the biological function of HBVDNAPTP1. The HBVDNAPTP1 coding sequence was cloned into a pGEM-T vector. Subsequent to sequencing, the HBVDNAPTP1 was subcloned into the bait plasmid pGBKT7 and transformed into yeast AH109. Western blotting confirmed the presence of HBVDNAPTP1 expression in the AH109 yeast strains. The transformed yeast AH109 cells were mated with Y187 yeast cells containing the leucocyte cDNA library pACT2 plasmids in 2X yeast extract peptone D-glucose adenine (YPDA) medium. For selection and screening, diploid yeast was plated on synthetic dropout medium (SD/-Trp-Leu-His-Ade) containing X-α-gal. Following sequencing and the verification of the open reading frames of positive colonies, four different proteins were obtained. To further confirm the interaction between HBVDNAPTP1 and the screened proteins, paired immunoglobulin-like type 2 receptor α (PILRA), one of the positive colonies, was cloned. The glutathione S-transferase pull-down in vitro assay and a co-immunoprecipitation in vivo assay were used to examine the interaction between HBVDNAPTP1 and PILRA, respectively. HBVDNAPTP1 may be involved in the negative regulation of the PILRA‑mediated Janus-activated kinase/signal tranducer and activator of transcription signaling pathway, and exert a positive effect on the initiation of monocyte apoptosis. These results contribute our knowledge of the biological functions of HBVDNAPTP1 and provide novel data to aid in the further analysis of the regulatory mechanism of this protein.

  4. Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore.

    Lee, Yi Chuan; Chan, Soh Ha; Ren, Ee Chee

    2008-11-01

    Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.

  5. Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2.

    Wang, Wei; Erbe, Amy K; Gallenberger, Mikayla; Kim, KyungMann; Carmichael, Lakeesha; Hess, Dustin; Mendonca, Eneida A; Song, Yiqiang; Hank, Jacquelyn A; Cheng, Su-Chun; Signoretti, Sabina; Atkins, Michael; Carlson, Alexander; Weiss, Jonathan M; Mier, James; Panka, David; McDermott, David F; Sondel, Paul M

    2016-12-01

    NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition. In some settings where an anticancer immunotherapeutic effect is likely mediated by NK cells, individuals with a KIR-ligand missing genotype have shown improved clinical outcome compared to individuals with an "all KIR-ligands present" genotype. In addition, patients receiving hematopoietic stem cell transplants for leukemia may do better if their donor has more activating KIR genes (i.e., KIR haplotype-B). In a recent multi-institution clinical trial of patients with metastatic renal cell carcinoma receiving high-dose IL2 (HD-IL2), 25 % of patients showed a complete or partial tumor response to this therapy. We genotyped KIR and KIR-ligand genes for these patients (n = 107) and tested whether KIR/KIR-ligand genotypes correlated with patient clinical outcomes. In these analyses, we did not find any significant association of KIR/KIR-ligand genotype (either KIR-ligand missing or the presence of KIR haplotype-B) with patient outcome in response to the HD-IL2 therapy.

  6. The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR A haplotype in patients with advanced-stage classic Hodgkin lymphoma

    Giorgio La Nasa

    2016-03-01

    Full Text Available Abstract Background Interim positron emission tomography after 2 cycles of ABVD (iPET-2 is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL, few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs. Methods We investigated KIR gene frequencies, KIR haplotypes, and KIR-ligand combinations in a cohort of 135 patients with advanced-stage classic Hodgkin lymphoma and 221 healthy controls. We furthermore evaluated the correlation of KIR genes and KIR haplotypes with the achievement of negative iPET-2. Results In the cohort of patients, the 5-year overall survival and progression-free survival were 93.6 and 79 %, respectively. Homozygosity for KIR A haplotype and the HLA-C1 KIR ligand (KIR-AA/C1C1 was significantly higher in healthy controls (15.7 vs. 4.8 %, p = 0.001. The KIR-AA genotype resulted to have a significant predictive power for achieving iPET-2 negativity (p = 0.039. Conclusions Homozygosity for KIR A haplotype offers protection against classic Hodgkin lymphoma. The association found for the KIR-AA genotype and achievement of negative iPET-2 suggests that KIR-AA could be used in clinical practice to enhance the chemosensitivity predictive power of iPET-2. Our results point to the possibility of adapting treatment strategies based on the combination of KIR biomarkers and PET scan.

  7. Expression of Leukocyte Inhibitory Immunoglobulin-like Transcript 3 Receptors by Ovarian Tumors in Laying Hen Model of Spontaneous Ovarian Cancer.

    Khan, Mohammad Faisal; Bahr, Janice M; Yellapa, Aparna; Bitterman, Pincas; Abramowicz, Jacques S; Edassery, Seby L; Basu, Sanjib; Rotmensch, Jacob; Barua, Animesh

    2012-04-01

    Attempts to enhance a patient's immune response and ameliorate the poor prognosis of ovarian cancer (OVCA) have largely been unsuccessful owing to the suppressive tumor microenvironment. Leukocyte immunoglobulin-like transcript 3 (ILT3) inhibitory receptors have been implicated in immunosuppression in several malignancies. The expression and role of ILT3 in the progression of ovarian tumors are unknown. This study examined the expression and association of ILT3 in ovarian tumors in laying hens, a spontaneous preclinical model of human OVCA. White Leghorn laying hens were selected by transvaginal ultrasound scanning. Serum and normal ovaries or ovarian tumors were collected. The presence of tumors and the expression of ILT3 were examined by routine histology, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction. In addition to stromal immune cell-like cells, the epithelium of the ovarian tumors also expressed ILT3 with significantly high intensity than normal ovaries. Among different subtypes of ovarian carcinomas, serous OVCA showed the highest ILT3 staining intensity, whereas endometrioid OVCA had the lowest intensity. Similar to humans, an immunoreactive protein band of approximately 55 kDa for ILT3 was detected in the ovarian tumors in hens. The patterns of ILT3 protein and messenger RNA expression by ovarian tumors in different subtypes and stages were similar to those of immunohistochemical staining. The results of this study suggest that laying hens may be useful to generate information on ILT3-associated immunosuppression in OVCA. This animal model also offers the opportunity to develop and test anti-ILT3 immunotherapy to enhance antitumor immunity against OVCA in humans.

  8. Leukocyte-associated immunoglobulin-like receptor-1 expressed in epithelial ovarian cancer cells and involved in cell proliferation and invasion

    Cao, Qizhi [Department of Immunology, Binzhou Medical University, Yantai (China); Fu, Aili [Department of Immunology, Binzhou Medical University, Yantai (China); The People' s Liberation Army 107 Hospital, Affiliated Hospital of Bin Zhou Medical University, Yantai (China); Yang, Shude [Institute of Fungi Science and Technology, Ludong University, Yantai (China); He, Xiaoli; Wang, Yue; Zhang, Xiaoshu; Zhou, Jiadi; Luan, Xiying [Department of Immunology, Binzhou Medical University, Yantai (China); Yu, Wenzheng, E-mail: bzywz2009@163.com [Department of Hemotology, The Hospital Affiliated Binzhou Medical University, Binzhou (China); Xue, Jiangnan, E-mail: xuejinagnan@263.net [Department of Immunology, Binzhou Medical University, Yantai (China)

    2015-03-06

    Previous studies have shown that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on most types of hamatopoietic cells and negatively regulate immune response, but the roles of LAIR-1 in tumor of the non-hematopoietic lineage have not been determined. Despite advances in therapy of epithelial ovarian cancer (EOC), many questions relating to EOC pathogenesis remain unanswered. The aim of this study was to investigate the clinical significance of LAIR-1 expression in EOC and explore the possible association between LAIR-1 and cancer. In this study, a tissue microarray containing 78 ovarian cancer cases was stained following a standard immunohistochemical protocol for LAIR-1 and the correlation of LAIR-1 expression with clinicopathologic features was assessed. LAIR-1 was detected to express in tumor cells of ovarian cancer tissues (73.1%) and EOC cell lines COC1 and HO8910, not in normal ovarian tissues. In addition, LAIR-1 expression correlates significantly with tumor grade (p = 0.004). Furthermore, down-regulation of LAIR-1 in HO8910 cells increased cell proliferation, colony formation and cell invasion. These data suggest that LAIR-1 has a relevant impact on EOC progression and may be helpful for a better understanding of molecular pathogenesis of cancer. - Highlights: • LAIR-1 is expressed in epithelial ovarian cancer cells. • LAIR-1 expression correlates significantly with tumor grade. • Down-regulation of LAIR-1 expression increased cell proliferation and invasion. • LAIR-1 may be a novel candidate for cancer diagnosis and therapy.

  9. Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains fusion in fishes and ray-finned fishes specific intron insertion after separation from zebrafish

    Kumar, Abhishek, E-mail: akumar@bot.uni-kiel.de [Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University at Kiel, Kiel (Germany); Bhandari, Anita [Molecular Physiology, Zoological Institute, Christian-Albrechts-University at Kiel, Kiel (Germany); Sarde, Sandeep J. [Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University at Kiel, Kiel (Germany); Goswami, Chandan [National Institute of Science Education and Research, Bhubaneswar, Orissa (India)

    2014-07-18

    Highlights: • C1 inhibitors of fishes have two Ig domains fused in the N-terminal end. • Spliceosomal introns gain in two Ig domains of selected ray-finned fishes. • C1 inhibitors gene is maintained from 450 MY on the same locus. • C1 inhibitors gene is missing in frog and lampreys. • C1 inhibitors of tetrapod and fishes differ in the RCL region. - Abstract: C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1′. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ∼450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys.

  10. Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

    Xue, Jiangnan, E-mail: xuejinagnan@263.net [Department of Immunology, Binzhou Medical University, Yantai 264003 (China); Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili [Department of Immunology, Binzhou Medical University, Yantai 264003 (China)

    2011-02-04

    Research highlights: {yields} LAIR-1 is expressed on human megakaryocytes from an early stage. {yields} Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. {yields} LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34{sup +}CD41a{sup +} and CD41a{sup +}CD42b{sup +} cells. LAIR-1 is also detectable in a fraction of human cord blood CD34{sup +} cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34{sup +} cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

  11. Down-regulation of Leucine-rich Repeats and Immunoglobulin-like Domain Proteins (LRIG1-3) in HP75 Pituitary Adenoma Cell Line

    GUO Dongsheng; HAN Lin; SHU Kai; CHEN Jian; LEI Ting

    2007-01-01

    Three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor. Real-time reverse transcription-polymerase chain reaction (RT-PCR) is a recently developed technique for quantitative assessment of specific RNA levels. In the current study, it was demonstrated that LRIG1-3 and EGFR mRNA was detected in human pituitary adenoma cell lines and a normal pituitary sample, with differences in the expression levels. Compared to the normal pituitary samples, the expression of LRIG1-3 in HP75 cell line was lower, but the expression of EGFR in HP75 cell line was higher. The results are consistent with LRIG1-3 being tumour suppressor genes, and LRIG genes decreasing the expression of EGFR. The ratio of EGFR/LRIG1 was increased at least 13-fold in HP75 cells compared with the normal pituitary cells, which was also the case for the ratio of EGFR/LRIG2 (14-fold increase in HP75) and EGFR/LRIG3 (11-fold increase in HP75). Further studies were needed to elucidate the explicit role of LRIG genes as negative regulators of oncogenesis in human pituitary adenoma.

  12. Killer cell immunoglobulin-like receptor and human leukocyte antigen gene profiles in a cohort of HIV-infected Mexican Mestizos.

    Garrido-Rodríguez, Daniela; Ávila-Ríos, Santiago; García-Morales, Claudia; Valenzuela-Ponce, Humberto; Ormsby, Christopher; Reyes-Gopar, Helena; Fernandez-Lopez, Juan Carlos; Reyes-Terán, Gustavo

    2016-10-01

    Killer cell immunoglobulin-like receptors (KIRs) represent the most polymorphic genes responsible for natural killer cell function, while human leukocyte antigen (HLA) class I molecules define and restrict cytotoxic T lymphocyte responses. Specific KIR, HLA, or KIR-HLA combinations have been implicated in the outcome of human immunodeficiency virus (HIV) disease. The remarkable polymorphism of KIR and HLA genes warrants descriptive gene frequency studies in different populations, as well as their impact on HIV disease progression in different immunogenetic contexts. We report KIR and HLA class I gene profiles of 511 unrelated HIV-infected Mexican Mestizo individuals from 18 states for whom genetic ancestry proportions were assessed. KIR and HLA gene profiles were compared between individuals from the north and central-south regions of the country and between individuals with higher European (EUR) or Amerindian (AMI) genetic ancestry component. A total of 65 KIR genotypes were observed, 11 harboring novel KIR gene combinations. A total of 164 HLA alleles were observed: 43 HLA-A, 87 HLA-B, and 34 HLA-C. Differences in the distribution of 12 HLA alleles were observed between individuals with higher AMI or EUR ancestry components (p < 0.05, q < 0.2). After correcting for genetic ancestry, only individual HLA alleles were associated with HIV disease progression, including a novel association with A*02:06, an Amerindian HLA allele associated with lower CD4+ T cell counts. No KIR effects were significant. Our results highlight the advantages of considering a detailed genetic stratification within populations when studying genetic profiles that could be implicated in disease-association studies.

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

    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.

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

    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

  15. Donor killer immunoglobulin-like receptor genes and reactivation of cytomegalovirus after HLA-matched hematopoietic stem-cell transplantation: HLA-C allotype is an essential cofactor

    Carolyn E. Behrendt

    2013-02-01

    Full Text Available Natural Killer (NK cells whose killer immunoglobulin-like receptors (KIR recognize human leukocyte antigen (HLA ligand are licensed for activity. In contrast, non-licensed NK cells display KIRs for which ligand is absent from the self genotype and are usually hyporesponsive. Surprisingly, non-licensed cells are active in tumor control after hematopoietic stem-cell transplantation (HSCT and dominate NK response to murine cytomegalovirus (CMV infection. From those reports, we hypothesized that control of human CMV early after HSCT is influenced by donor KIR genes whose HLA ligand is absent-from-genotype of HLA-matched donor and recipient. To investigate, we studied CMV reactivation through Day 100 after grafts involving CMV-seropositive donor and/or recipient. A multivariate proportional rates model controlled for variability in surveillance and established covariates including acute graft-versus-host disease; statistical significance was adjusted for testing of multiple KIRs with identified HLA class I ligand (2DL1, 2DL2/3, 2DS1, 2DS2, full-length 2DS4, 3DL1/3DS1, 3DL2. Among HSCT recipients (n=286, CMV reactivation-free survival time varied with individual donor KIR genes evolutionarily-specific for HLA-C: when ligand was absent from the donor/recipient genotype, inhibitory KIRs 2DL2 (P<0.0001 and 2DL1 (P=0.015 each predicted inferior outcome, and activating KIRs 2DS2 (P<0.0001, 2DS1 (P=0.016, and 2DS4 (P=0.016 each predicted superior outcome. Otherwise, with ligand present-in-genotype, donor KIR genes had no effect. In conclusion, early after HLA-matched HSCT, individual inhibitory and activating KIR genes have qualitatively different effects on risk of CMV reactivation; unexpectedly, absence of HLA-C ligand from the donor/recipient genotype constitutes an essential cofactor in these associations. Being KIR and HLA-C specific, these findings are independent of licensing via alternate NK cell receptors (NKG2A, NKG2C that recognize HLA-E.

  16. Role of Paired Immunoglobulin-like Receptor B in Nerve Regeneration (review)%配对免疫球蛋白样受体B与神经再生

    肖岚; 王永堂; 位景香; 舒亚海; 鲁秀敏; 余瑛

    2016-01-01

    It is difficult for regeneration of central nervous system (CNS) in adult mammals, and myelin-associated inhibitors (MAIs) are believed to be major contributors. Paired immunoglobulin-like receptor B (PirB), as a co-receptor of MAIs, and expresses highly in CNS after injury, plays a vital role in the signal transduction of inhibition in the injured CNS. Knockout or block of PirB in vitro and in vivo may promote the neuro-regeneration after spinal cord injury or hypoxic-ischemic brain damage, release the damage induced byβ-amyloid in Al-zheimer's disease, recover the neural function in brain inflammation models, improve the reconstruction of vision after optic nerve injury, and so on. PirB may be a potential therapeutic target for neuro-regeneration and synaptic plasticity.%成年哺乳动物中枢神经系统(CNS)损伤后难以恢复,主要是由于中枢微环境中髓磷脂相关抑制因子介导的神经生长抑制作用引起的。配对免疫球蛋白样受体B (PirB)作为其主要受体之一,在CNS损伤后高表达,参与神经生长抑制信号的传递。敲除或阻断PirB,能促进脊髓损伤动物神经再生,缓解β-淀粉样蛋白对阿尔茨海默病的病理影响,显著诱导缺氧缺血损伤后皮层神经元轴突再生,恢复中枢炎性神经病模型动物的神经功能,视神经损伤后的视觉重塑功能加强。

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

    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...

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

    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. A relevância das células natural killer (NK e killer immunoglobulin-like receptors (KIR no transplante de células-tronco hematopoéticas (TCTH The relevance of natural killer (NK cells and killer immunoglobulin-like receptors (KIR in hematopoietic stem cell transplantation (HSCT

    Aline Almeida-Oliveira

    2008-08-01

    Full Text Available As células natural killer (NK foram identificadas há mais de 30 anos por sua capacidade de matar células tumorais e infectadas por vírus sem precisar de sensibilização prévia. No entanto, a forma como as células NK matam seus alvos ficou desconhecida por muito tempo. Na década de 90, a partir de várias observações, foi proposto que as células NK matariam células com a expressão diminuída de antígeno leucocitário humano (HLA, protegendo as células autólogas normais, o que ficou conhecido como hipótese do missing-self. Esta teoria foi confirmada através da descoberta de vários receptores, principalmente os da família killer immunoglobulin-like receptors (KIR, que reconhecem moléculas de HLA de classe I. Estes novos conceitos levaram à busca da importância dos receptores KIR no transplante de células-tronco hematopoéticas (TCTH. Foi sugerido que as disparidades de HLA entre o doador e o paciente poderiam ser reconhecidas por células NK levando à aloreatividade, o que ajudaria no efeito enxerto contra leucemia. No entanto, apesar de alguns resultados promissores, até hoje, os diferentes estudos sobre o assunto não chegaram a um consenso. Nesta revisão, será abordada a relevância das células NK e dos receptores KIR nos diferentes tipos de TCTH.Natural killer (NK cells were identified over 30 years ago by their ability to kill cancer and virally infected cells without prior sensitization. For years the recognition mechanisms of target cells were unknown, until the 1990s when the "missing-self" hypothesis was proposed. According to this theory, although tolerant to normal autologous cells, NK cells can recognize and attack cells that have down-regulated human leukocyte antigen (HLA class I molecules. The discovery of killer immunoglobulin-like receptors (KIR that specifically recognize HLA class I molecules corroborated this hypothesis. These new concepts point to the importance of studying KIR in hematopoietic stem

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

    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.

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

    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

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

    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

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

    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

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

    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...

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

    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...

  6. The frequencies of Killer immunoglobulin-like receptors and their HLA ligands in chronic inflammatory demyelinating polyradiculoneuropathy are similar to those in Guillian Barre syndrome but differ from those of controls, suggesting a role for NK cells in pathogenesis.

    Blum, Stefan; Csurhes, Peter; McCombe, Pamela

    2015-08-15

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired inflammatory neuropathy, which has similar clinical and pathological features to Guillain-Barré Syndrome (GBS), but differs in time course. We investigated the frequency of genes encoding Killer immunoglobulin-like receptors and their HLA ligands in subjects with CIDP, in subjects with GBS and in healthy controls. There were no differences in KIR gene frequency among the 3 groups. The gene frequencies for HLA-B Bw4-I were significantly greater in CIDP than HC, but did not differ from GBS. The frequency of the combination of 3DL1/HLA-B Bw4I was greater in CIDP than HC, but did not differ from that of GBS. These data raise the possibility of NK cell function being an important factor in the pathogenesis of CIDP.

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

    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.

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

    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

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

    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...

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

    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...

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

    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.

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

    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),

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

    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

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

    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.

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

    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.

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

    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...

  17. Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

    Ning Pan

    2013-01-01

    Full Text Available To investigate whether killer cell immunoglobulin-like receptor (KIR and human leukocyte antigen (HLA genetic background could influence the onset age of hepatocellular carcinoma (HCC in patients with hepatitis B virus (HBV infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P=0.04 for KM analysis; HR = 1.70, P=0.004 for multivariate Cox model. We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells in the progress of HBV-related HCC development.

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

    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.

  19. Recent Advances in Nucleic Acid Binding Aspects of Berberine Analogs and Implications for Drug Design.

    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.

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

    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.

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

    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.

  2. Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.

    An, Hongyan; Lim, Chai; Guillemin, Gilles J; Vollmer-Conna, Ute; Rawlinson, William; Bryant, Katherine; Tedla, Nicodemus

    2016-01-01

    Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.

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

    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.

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

    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.

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

    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.

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

    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

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

    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...

  9. Impact of "Killer Immunoglobulin-Like Receptor /Ligand" Genotypes on Outcome following Surgery among Patients with Colorectal Cancer: Activating KIRs Are Associated with Long-Term Disease Free Survival.

    Kemal Beksac

    Full Text Available Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS. Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4 genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR and A-Bw4 (ligand for inhibitory KIR3DL1 were observed more frequently (p=0.017 and p=0.024; and KIR2DS2 and KIR2DS3 (both activating KIRs were observed less frequently (p=0.005 and p=0.043. Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07. The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023. KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028. The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004. In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs

  10. Impact of "Killer Immunoglobulin-Like Receptor /Ligand" Genotypes on Outcome following Surgery among Patients with Colorectal Cancer: Activating KIRs Are Associated with Long-Term Disease Free Survival.

    Beksac, Kemal; Beksac, Meral; Dalva, Klara; Karaagaoglu, Ergun; Tirnaksiz, M Bulent

    2015-01-01

    Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of

  11. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower

    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...

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

    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

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

    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

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

    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...

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

    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...

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

    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

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

    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....

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

    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).

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

  9. The study of kuller cell immunoglobulin-like receptor 3DL2 gene polymorphisms and pre-eclampsia%KIR3DL2基因多态性与子痫前期的相关性研究

    王小兰; 张为远; 王琪; 孙成娟

    2009-01-01

    Objective To analyze a presumed association of gene polymorphism of killer cell immunoglobulin-like receptor three domains, long cytoplasmic tail, 2 (KIR3DL2) gene with pre-eclampsia. Methods The KIR3DL2 gene A52G in exon 3 and C32T in exon 9 polymorphism were determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) in 95 pre-eclampsia and 91 normal pregnant women. Results There was significant difference between two group in exon 3 in terms of genotypes and allele (P 0.05). Conclusion The A52G polymorphism in exon 3 and the frequencies of C32T in exon 9 of KIR3DL2, gene polymorphism are associated with the pathogenesis of pre-eclampsia, But it has no correlation with the severity of preeclampsia.%目的 探讨自然杀伤细胞免疫球蛋白样受体基因(KIR3DL2)第3外显子52位点(A/G)和第9外显子32位点(C/T)突变与子痫前期发病的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对95例子痫前期患者和91名正常妊娠妇女的KIR3DL2基因第3外显子A52G、第9外显子C32T突变进行检测.结果 KIR3DL2基因第3外显子52位点基因型频率分布及等位基因的频率分布在两组间比较差异均有统计学意义(均P<0.05).子痫前期组第9外显子基因型频率与对照组的基因型频率比较差异有统计学意义(P<0.05).轻度子痫前期与重度子痫前期在上述两位点的基因型频率分布及等位基因的频率分布比较差异均无统计学意义.结论 KIR3DL2基因第3外显子A52G突变与子痫前期的发病有关,第9外显子32位点基因型频数分布与子痫前期发病有关,但与子痫前期的发病程度无关.

  10. Effects of natural killer cells with killer immunoglobulin-like receptors incompa-tibility on breast cancer cells%KIR不相合的NK细胞对乳腺癌细胞的体外杀伤作用

    叶韵斌; 周智锋; 郑蕊蕊; 陈强; 林建银; 李洁羽

    2007-01-01

    目的:研究自然杀伤(natural killer, NK)细胞表面杀伤细胞免疫球蛋白样受体(killer immunoglobulin-like receptor,KIR)和HLA-Cw配体不相合的异基因NK细胞对乳腺癌细胞的体外杀伤作用;分析杀伤活化受体NKG2D及其MICA配体表达水平与NK细胞对乳腺癌细胞杀伤敏感性之间的关系.方法:取10例健康人及5例乳腺癌患者外周血10 ml,采用MACS系统NK细胞免疫磁珠分选试剂盒负向分选高纯度NK细胞.取乳腺癌细胞(MCF-7、MDA-MB-435s和SK-Br3)和NK细胞各1×105个,碱裂解法抽提DNA,PCR-SSP方法分别检测HLA-Cw位点、KIR位点表达.MTT法检测KIR相合与不相合组的NK细胞对乳腺癌细胞的杀伤率.流式细胞术检测NK细胞NKG2D表达水平以及RT-PCR方法检测乳腺癌细胞MICA表达.结果:MACS系统分选出的NK细胞,经流式细胞术检测,其纯度在90%以上;KIR与 HLA-Cw相合组的NK细胞对乳腺癌细胞株的杀伤率明显高于不相合组,G1组和G2组NK细胞对MDA-MB-435s(G1组)杀伤率分别为(73.2±14.5)%和(34.2±7.6)%,对SK-Br3(G1组)杀伤率为(67.3±12.5)%和(36.5±7.7)%,而对MCF-7(G2组)杀伤率分别为(36.7±8.5)%和(76.5±11.7)%.结果还显示,3株乳腺癌细胞均表达MICA分子;NK细胞与MCF-7细胞共培养,可上调NK细胞表面NKG2D的表达.结论:NK细胞对乳腺癌细胞的杀伤并非由KIR的不相合机制介导;乳腺癌细胞表面表达的MICA分子可上调NK细胞表面NKG2D的表达,激发NK细胞对乳腺癌细胞的细胞毒效应.

  11. Comparative Study on the Typing of Killer Immunoglobulin-Like Receptor by Using Two Different Genotyping Methods%两种不同的KIR基因分型方法的对比研究

    金士正; 甄建新; 何柳媚; 徐筠娉; 邓志辉

    2012-01-01

    目的 探讨常用的序列特异性引物-PCR(PCR-SSP)及流式序列特异性寡核苷酸探针(Flow-rSSO)杂交方法在杀伤细胞免疫球蛋白样受体(KIR)框架基因分型结果中的符合率和准确性.方法 随机选择2011年6月77例深圳造血干细胞捐献者的外周血样,分别用PCR-SSP及Flow-rSSO商品化试剂盒进行KIR框架基因定型,分别通过凝胶电泳图及HLA Fusion 2.0 Research软件分析法,分析结果的一致性.对初检结果不一致的样本,采用同一厂家、不同批号的商品化试剂盒进行复检,并采用美国国立卫生研究院癌症研究所KIR PCR-SSP方法进行检测.结果 77例样本中,75例完全一致,另2例(2.6%) KIR2DL2的结果不一致,PCR-SSP方法对KIR 2DL2的初检、复检检测结果均为阴性,但用Flow-rSSO Lot#004批号试剂盒检测结果为阳性.更换新的Flow-rSSO Lot# 005批号试剂盒复检,结果与PCR-SSP方法的检测结果相一致.结论 为保证KIR基因分型的准确性,开展KIR基因分型的室内、室间质控工作至关重要.%Objective To explore the accuracy of killer immunoglobulin-like receptor (KIR) genotyping by using the sequence specific primer-PCR (PCR-SSP)and flow reverse sequence specific oligonucleotide probe(Flow-rSSO)assays.Methods A total of 77 samples from randomly selected stem cell volunteer donors in Shenzhen were subjected to KIR genotyping using the commercial PCR-SSP and Flow-rSSO kits,respectively.The accordance of KIR genotyping results was evaluated and the reason causing the different results was analyzed in this study.Samples with inconclusive and different genotyping results were retested using the same PCR SSP and Flow-rSSO commercial kits with updated lot number and also typed by PCR-SSP method established by National Cancer Institute. Results In the 77 tested samples,the KIR genotypes of 75 samples were in accordance by PCR-SSP and Flow rSSO commercial kit. However,the other two samples showed different results

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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...

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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  10. Nucleic acid-binding glycoproteins which solubilize nucleic acids in dilute acid: re-examination of the Ustilago maydis glycoproteins

    Unrau, P.; Champ, D.R.; Young, J.L.; Grant, C.E.

    1980-01-01

    Holloman reported the isolation from Ustilago maydis of a glycoprotein which prevented the precipitation of nucleic acids in cold 5% trichloroacetic acid. Two glycoprotein fractions from U. maydis with this nucleic acid-solubilizing activity were isolated in our laboratory using improved purification procedures. The activity was not due to nuclease contamination. The glycoproteins are distinguished by: their ability to bind to concanavalin A-Sepharose; their differential binding to double- and single-stranded deoxyribonucleic acid, and to ribonucleic acid; their molecular weights (46,000 and 69,000); and the relative amounts present in growing versus nongrowing cells. Both fractions required sulfhydryl-reducing conditions for optimal yields, specific activity, and stability. Nucleic acid binding was cooperative, the minimum number of glycoproteins required to make a native T7 DNA molecule soluble in dilute acid being estimated at 2 and 15, respectively.

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

    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.

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

    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.

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

    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

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

    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

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

    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 ...

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

    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...

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

    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

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

    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

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

    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.

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

    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. Purification of Two Novel Sugar Acid-binding Lectins from Haplomitrium Mnioides (bryophyte, Plantae) and their Preliminary Characterization.

    Masuzaki, Hiroaki; Hosono, Masahiro; Nitta, Kazuo

    2017-01-01

    Two novel sugar acid-binding lectins were purified from Haplomitrium mnioides (Lindb.) Schust. using a procedure consisting of ammonium sulfate precipitation, G-50 gel filtration, hydroxyapatite chromatography, and HW-50 gel filtration. We reported their partial physicochemical properties: molecular weight, affinity for carbohydrates and organic acids, pH stability, and dependence of their hemagglutination activity on metal ions. We also determined their N-terminal amino acid sequences. H. mnioides lectins (HMLs) were monomers (one with a molecular weight of approximately 27 kDa, and the other with a molecular weight of approximately 105 kDa) under both nonreducing and reducing conditions. They were named HML27 and HML105, respectively. Both HMLs had an affinity for N-acetylneuraminic acid, D-glucuronic acid, D-glucaric acid, bovine submaxillary mucin, heparin, and organic acids, such as citrate, 2-oxoglutaric acid, and D-2-hydroxyglutarate. Furthermore, HML27 had an affinity for α-D-galacturonic acid, D-malate, L-malate, and pyruvate, while HML105 had an affinity for D-gluconic acid. HML27 and HML105 are novel plant lectins: they have an affinity for sugar acids and organic acids and specifically recognize the carboxyl group, and there is no homology between their N-terminal amino acid sequences and those of the previously described lectins and agglutinins.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  7. Techno-functional properties and in vitro bile acid-binding capacities of tamarillo (Solanum betaceum Cav.) hydrocolloids.

    Gannasin, Sri Puvanesvari; Adzahan, Noranizan Mohd; Mustafa, Shuhaimi; Muhammad, Kharidah

    2016-04-01

    Hydrocolloids were extracted from seed mucilage and the pulp fractions from red tamarillo (Solanum betaceum Cav.) mesocarp, and characterisation of their techno-functional properties and in vitro bile acid-binding capacities was performed. The seed mucilage hydrocolloids that were extracted, using either 1% citric acid (THC) or water (THW), had a good foaming capacity (32-36%), whereas the pulp hydrocolloids that were extracted, using 72% ethanol (THE) or 20mM HEPES buffer (THH), had no foaming capacity. The pulp hydrocolloid, however, possessed high oil-holding and water-holding capacities in the range of 3.3-3.6 g oil/g dry sample and 25-27 g water/g dry sample, respectively. This enabled the pulp hydrocolloid to entrap more bile acids (35-38% at a hydrocolloid concentration of 2%) in its gelatinous network in comparison to commercial oat fibre and other hydrocolloids studied. The exceptional emulsifying properties (80-96%) of both hydrocolloids suggest their potential applications as food emulsifiers and bile acid binders.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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/.

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

    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

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

    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...

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

    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.

  9. Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation.

    Bao, Xiaojing; Wang, Miao; Zhou, Huifen; Zhang, Huanhuan; Wu, Xiaojin; Yuan, Xiaoni; Li, Yang; Wu, Depei; He, Jun

    2016-02-01

    Donor killer immunoglobulin-like receptor (KIR) group B profiles (Bx) and homozygous of centromeric motif B (Cen-B/B) are the most preferable KIR gene content motifs for hematopoietic stem cell transplantation (HSCT). The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (regardless of number) were observed for standard-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients in this 4-year retrospective study. A total of 210 Chinese patients who underwent unrelated donor HSCT were investigated. Donor KIR profile Bx was associated with significantly improved overall survival (OS; P = .026) and relapse-free survival (RFS; P = .021) and reduced nonrelapse mortality (NRM; P = .017) in AML/MDS patients. A significantly lower survival rate was observed for transplants from Bx1 donors compared with Bx2, Bx3, and Bx4 donors for patients in first complete remission (n = 82; OS: P = .024; RFS: P = .021). Transplant from donors with Cen-B resulted in improved OS (HR = .256; 95% CI, .084 to .774; P = .016) and RFS (HR = .252; 95% CI, .084 to .758; P = .014) in AML/MDS patients at standard risk. However, this particular effect did not increase with a higher number of Cen-B motifs (cB/B versus cA/B; OS: P = .755; RFS: P = .768). No effect was observed on high-risk AML/MDS, acute lymphoblastic leukemia/non-Hodgkin lymphoma, and chronic myelogenous leukemia patients. Avoiding the selection of HSCT donors of KIR profile Bx1 is strongly advisable for standard-risk AML/MDS patients. The presence of the Cen-B motif rather than its number was more important in donor selection for the Chinese population.

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

    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

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

    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

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

    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

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

    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

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

    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.

  15. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake.

    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...

  16. Amino acid differences in glycoproteins B (gB, C (gC, H (gH and L(gL are associated with enhanced herpes simplex virus type-1 (McKrae entry via the paired immunoglobulin-like type-2 receptor α

    Chowdhury Sona

    2012-06-01

    Full Text Available Abstract Background Herpes simplex virus type-1 (HSV-1 enters into cells via membrane fusion of the viral envelope with plasma or endosomal membranes mediated by viral glycoproteins. HSV-1 virions attach to cell surfaces by binding of viral glycoproteins gC, gD and gB to specific cellular receptors. Here we show that the human ocular and highly neurovirulent HSV-1 strain McKrae enters substantially more efficiently into cells via the gB-specific human paired immunoglobulin-like type-2 receptor-α (hPILR-α. Comparison of the predicted amino acid sequences between HSV-1(F and McKrae strains indicates that amino acid changes within gB, gC, gH and gL may cause increased entry via the hPILR- α receptor. Results HSV-1 (McKrae entered substantially more efficiently than viral strain F in Chinese hamster ovary (CHO cells expressing hPIRL-α but not within CHO-human nectin-1, -(CHO-hNectin-1, CHO-human HVEM (CHO-hHVEM or Vero cells. The McKrae genes encoding viral glycoproteins gB, gC, gD, gH, gL, gK and the membrane protein UL20 were sequenced and their predicted amino acid (aa sequences were compared with virulent strains F, H129, and the attenuated laboratory strain KOS. Most aa differences between McKrae and F were located at their gB amino termini known to bind with the PILRα receptor. These aa changes included a C10R change, also seen in the neurovirulent strain ANG, as well as redistribution and increase of proline residues. Comparison of gC aa sequences revealed multiple aa changes including an L132P change within the 129-247 aa region known to bind to heparan sulfate (HS receptors. Two aa changes were located within the H1 domain of gH that binds gL. Multiple aa changes were located within the McKrae gL sequence, which were preserved in the H129 isolate, but differed for the F strain. Viral glycoproteins gD and gK and the membrane protein UL20 were conserved between McKrae and F strains. Conclusions The results indicate that the observed

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

    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.

  18. 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

    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.

  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.

    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.

  20. 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.

    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.

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

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

    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.

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

    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.

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

    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.

  5. Crystallization and preliminary X-ray diffraction analysis of the sialic acid-binding domain (VP8*) of porcine rotavirus strain CRW-8

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  10. Anti-HIV Ⅰ/Ⅱ Activity and Molecular Cloning of a Novel Mannose/Sialic Acid-binding Lectin from Rhizome of Polygonatum cyrtonema Hua

    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.

  11. Correlation between killer cell immunoglobulin-like receptors genes and pre-eclampsia%杀伤细胞免疫球蛋白样受体基因多态性与子痫前期发病的相关性

    李源; 赵艳晖; 张为远; 崔满华

    2008-01-01

    objective To analyze the killer cell immunoglobulin-like receptors(KIR)gene polymorphism of pre-eclampsia patients and approach the correlation between KIR genes and pre-eclampsia.Methods The KIR gene polymorphisms of 71 pre-eclampsia patients and 100 healthy pregnant women were detected by PCR-SSP.The KIR2DL4 mRNA level in placentas from pre-eclampsia and gestational normal pregnancies were quantified by real time RT-PCR.Forty pre-eclampsia patients and 38 healthy pregnant women were detected for single nucleotide polymorphisms(SNP)in the gene coding and joint areas between introns and extrons by directly sequencing techniques of KIR2DL4 genomic DNA.Finally,all alleles and genotypes of KIR2DL4 gene were case-control studied.Result Distributions of some relatively activating KIR genotypes shewed a significant association with pre-eclampsia.Real-time RT-PCR showed that KIR2DL4 mRNA can be measured both in placenta of women with pre-eclampsia being of pre-eclampsia waft significantly lower than that of normal pregnancy.only as much as 0.276 times that of controls.We identified 18 polymorphisms,of which,7 were first reported.But no significant differences in genotype distributions or allele frequencies were observed in these SNPs between cases and controls.Conclusion The distributions of some relatively activating KIR genotypes showed a significant association with pre-eclampsia,which indicates that the polymorphism of KIR genes may be associated with the genetic predisposition to pre-eclampsia.And because the expression of KIR2DL4 mRNA in the placentas of cases wag significantly lower than control group,it is speculated that the decrease of KIR2DL4 expression in placenta may participate in the pathogenesis of pre-eclampsia.%目的 探讨杀伤细胞免疫球蛋白样受体(KIR)基因多态性(SNP)与子痫前期发病的相关性.方法 序列特异性引物PCR(PCR-SSP)技术检测子痫前期患者71例(子痫前期组)和正常孕妇100例(对照组)的外周

  12. In vitro bile acid binding of mustard greens, kale, broccoli, cabbage and green bell pepper improves with sautéing compared with raw or other methods of preparation.

    Bile acid binding capacity has been related to cholesterol-lowering potential of foods and food fractions. Lowered recirculating bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of can...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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).

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

    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

  19. MYB elongation is regulated by the nucleic acid binding of NFκB p50 to the intronic stem-loop region.

    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.

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

    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.

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

    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.

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

    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.

  3. Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae.

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

  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

    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

    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).

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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

  5. [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].

    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.

  6. 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

    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

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

    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.

  8. 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.

    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.

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

    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.

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

    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.

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

    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.

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

    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

  13. 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

    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.

  14. 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.

    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

  15. Design, synthesis, and anti-inflammatory evaluation of a series of novel amino acid-binding 1,5-diarylpyrazole derivatives

    Ming-hui LI; Lin-lin YIN; Mao-jun CAI; Wei-yu ZHANG; Yue HUANG; Xin WANG; Xing-zu ZHU; Jing-kang SHEN

    2005-01-01

    Aim: To design and synthesize a series of novel amino acid-binding 1,5-diarylpyrazole derivatives, which are intended to act as prodrugs with better aqueous solubility than celecoxib, and which will exert potent anti-inflammatory activities after being converted to their parent compounds in vivo.Methods: To introduce an amino acid, celecoxib analogs containing amino or methylamino group were synthesized first through multi-step chemical reactions.All the synthesized compounds were screened in an intact cell-based assay in vitro and in carrageenan-induced mouse paw edema in vivo.Some active compounds were selected for further evaluation in a carrageenan-induced rat paw edema model.The preliminary pharmacokinetics experiments were conducted using high performance liquid chromatography/mass spectrometry (HPLC/MS).Results: Celecoxib, 6 of the 1,5-diarylpyrazole class of celecoxib analogs, and their amino acid derivatives (hydrochloride salts) were synthesized.In vitro screening, the hydrochloride salts showed decreased inhibitory effects on cyclooxygenase (COX)-1 and COX-2 compared with their parent compounds, but some exhibited potent anti-inflam-matory activity in vivo.Compound 4a was selected for further evaluation, and its anti-inflammatory effect was equivalent to that of celecoxib after oral administration in the carrageenan-induced rat paw edema model.At three doses (25 mg/kg,50 mg/kg, and 100 mg/kg) the percentage inhibition on edema was 20.7%, 52.6%,and 62.6% (for compound 4a) and 27.8%, 38.4%, and 40.1% (for celecoxib),respectively.Preliminary pharmacokinetic evaluations support the hypothesis that compound 4a was actually converted to its parent compound, compound 4.Conclusion: The compound bound with amino acid acts like prodrug, which can exert anti-inflammatory effect similar to celecoxib after being converted to its parent compound.This finding will be of great benefit in carrying out structural modifications of prodrug-like selective COX-2 inhibitors.

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

    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

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

    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.

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

    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

  19. 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

    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.

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

    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

  1. 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

    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...

  2. 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

    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.

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

    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.

  4. 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

    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...

  5. Two types of antibodies are induced by vaccination with A/California/2009 pdm virus: binding near the sialic acid-binding pocket and neutralizing both H1N1 and H5N1 viruses.

    Nobuko Ohshima

    Full Text Available Many people have a history of catching the flu several times during childhood but no additional flu in adulthood, even without vaccination. We analyzed the total repertoire of antibodies (Abs against influenza A group 1 viruses induced in such a flu-resistant person after vaccination with 2009 H1N1 pandemic influenza virus. They were classified into two types, with no exceptions. The first type, the products of B cells newly induced through vaccination, binds near the sialic acid-binding pocket. The second type, the products of long-lived memory B cells established before vaccination, utilizes the 1-69 VH gene, binds to the stem of HA, and neutralizes both H1N1 and H5N1 viruses with few exceptions. These observations indicate that the sialic acid-binding pocket and its surrounding region are immunogenically very potent and majority of the B cells whose growth is newly induced by vaccination produce Abs that recognize these regions. However, they play a role in protection against influenza virus infection for a short period since variant viruses that have acquired resistance to these Abs become dominant. On the other hand, although the stem of HA is immunogenically not potent, the second type of B cells eventually becomes dominant. Thus, a selection system should function in forming the repertoire of long-lived memory B cells and the stability of the epitope would greatly affect the fate of the memory cells. Acquisition of the ability to produce Abs that bind to the stable epitope could be a major factor of flu resistance.

  6. 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)

    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.

  7. The immunoglobulin-like genetic predetermination of the brain: the protocadherins, blueprint of the neuronal network

    Hilschmann, N.; Barnikol, H. U.; Barnikol-Watanabe, S.; Götz, H.; Kratzin, H.; Thinnes, F. P.

    2001-01-01

    The morphogenesis of the brain is governed by synaptogenesis. Synaptogenesis in turn is determined by cell adhesion molecules, which bridge the synaptic cleft and, by homophilic contact, decide which neurons are connected and which are not. Because of their enormous diversification in specificities, protocadherins (pcdhα, pcdhβ, pcdhγ), a new class of cadherins, play a decisive role. Surprisingly, the genetic control of the protocadherins is very similar to that of the immunoglobulins. There are three sets of variable (V) genes followed by a corresponding constant (C) gene. Applying the rules of the immunoglobulin genes to the protocadherin genes leads, despite of this similarity, to quite different results in the central nervous system. The lymphocyte expresses one single receptor molecule specifically directed against an outside stimulus. In contrast, there are three specific recognition sites in each neuron, each expressing a different protocadherin. In this way, 4,950 different neurons arising from one stem cell form a neuronal network, in which homophilic contacts can be formed in 52 layers, permitting an enormous number of different connections and restraints between neurons. This network is one module of the central computer of the brain. Since the V-genes are generated during evolution and V-gene translocation during embryogenesis, outside stimuli have no influence on this network. The network is an inborn property of the protocadherin genes. Every circuit produced, as well as learning and memory, has to be based on this genetically predetermined network. This network is so universal that it can cope with everything, even the unexpected. In this respect the neuronal network resembles the recognition sites of the immunoglobulins.

  8. 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

    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.

  9. 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

    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.

  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.

    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.

  11. 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

    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.

  12. 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

    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

  13. 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

    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。

  14. 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

    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

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

    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).

  16. 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.

    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.

  17. 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

    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 by a p38 MAPK inhibitor as well as short interference RNA knockdown of p38 MAPK expression significantly decreased cell death and increased the cell viability of SBL-treated MDA-MB231 cells. H103A, an SBL mutant lacking in RNase activity, showed decreased SBL-induced cell death compared with native SBL. However, the loss of RNase activity of SBL had no effect on its internalization into cells. The H103A mutant also displayed decreased phosphorylation of p38 MAPK. Moreover, SBL promoted caspase-3/7 activation followed by a cleavage of poly (ADP-ribose)-polymerase, whereas the SBL mutant, H103A, lost this ability. The SBL-induced caspase-3/7 activation was suppressed by the p38 MAPK inhibitor, SB203580, as well as pan-caspase inhibitor, zVAD-fmk. In the presence of zVAD-fmk, the SBL-induced cell death was decreased. In addition, the cell viability of SBL-treated MDA-MB231 cells recovered by zVAD-fmk treatment. Taken together, our results suggest that the RNase activity of SBL leads to breast cancer cell death through the activation of p38 MAPK followed by the activation of caspase-3/7. PMID:27513956

  18. 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

    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。

  19. 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.

    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.

  20. 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.

    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.

  1. 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.

    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.

  2. 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.

    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.

  3. 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.

    Kariya, Yukiko; Tatsuta, Takeo; Sugawara, Shigeki; Kariya, Yoshinobu; Nitta, Kazuo; Hosono, Masahiro

    2016-10-01

    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 ribonuclease (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 by a p38 MAPK inhibitor as well as short interference RNA knockdown of p38 MAPK expression significantly decreased cell death and increased the cell viability of SBL-treated MDA‑MB231 cells. H103A, an SBL mutant lacking in RNase activity, showed decreased SBL-induced cell death compared with native SBL. However, the loss of RNase activity of SBL had no effect on its internalization into cells. The H103A mutant also displayed decreased phosphorylation of p38 MAPK. Moreover, SBL promoted caspase‑3/7 activation followed by a cleavage of poly (ADP-ribose)-polymerase, whereas the SBL mutant, H103A, lost this ability. The SBL-induced caspase‑3/7 activation was suppressed by the p38 MAPK inhibitor, SB203580, as well as pan-caspase inhibitor, zVAD-fmk. In the presence of zVAD-fmk, the SBL-induced cell death was decreased. In addition, the cell viability of SBL-treated MDA‑MB231 cells recovered by zVAD-fmk treatment. Taken together, our results suggest that the RNase activity of SBL leads to breast cancer cell death through the activation of p38 MAPK followed by the activation of caspase‑3/7.

  4. 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.

    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.

  5. 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

    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

  6. 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

    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。

  7. 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

    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

  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

    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

    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.

    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. Leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) is a modulator of FGFR1

    Kim, S.D.; Liu, J.L.; Roscioli, T.; Buckley, M.F.; Yagnik, G.; Boyadjiev, S.A.; Kim, J.

    2012-01-01

    Fibroblast growth factor receptors (FGFRs) play critical roles in craniofacial and skeletal development via multiple signaling pathways including MAPK, PI3K/AKT, and PLC-?. FGFR-mediated signaling is modulated by several regulators. Proteins with leucine-rich repeat (LRR) and/or immunoglobulin (IG)

  12. The Immunoglobulin-like Gene spe-45 Acts during Fertilization in Caenorhabditis elegans like the Mouse Izumo1 Gene.

    Nishimura, Hitoshi; Tajima, Tatsuya; Comstra, Heather Skye; Gleason, Elizabeth J; L'Hernault, Steven W

    2015-12-21

    The Caenorhabditis elegans spe-9 class genes, which show specific or predominant expression in the male germline, are indispensable for fertilization [1, 2]. However, due to the rapid evolution of genes involved in reproduction, we do not currently know if there are spe-9 class genes in mammals that play similar roles during fertilization to those found in C. elegans. In mice, the Izumo1 gene encodes a sperm-specific transmembrane (TM) protein with a single immunoglobulin (Ig)-like domain that is absolutely required for gamete fusion [3, 4]. In this study, we hypothesized that C. elegans has a new member of the spe-9 class genes coding for an IZUMO1-like protein. We screened C. elegans microarray data [5, 6] to identify male germline-enriched genes that encode membrane proteins with Ig-like domains. A deletion (tm3715) in one such gene (F28D1.8) caused hermaphrodites to show a male germline-dependent self-sterility, so we have named it spe-45. Mutant spe-45 worms seemed to normally undergo spermatogenesis (spermatid production by meiosis) and spermiogenesis (spermatid activation into actively motile spermatozoa). spe-45 mutant spermatozoa, however, could not complete gamete fusion, which is a characteristic of all spe-9 class mutants [1, 2]. Moreover, spe-45 self-sterile worms were rescued by a transgene expressing chimeric SPE-45 protein in which its Ig-like domain was replaced by the Ig-like domain from mouse IZUMO1. Hence, C. elegans SPE-45 and mouse IZUMO1 appear to have retained a common function(s) that is required during fertilization.

  13. Analysis of Killer Cell Immunoglobulin-like Receptor Genes and Their HLA Ligands in Iranian Patients with Ankylosing Spondylitis.

    Mahmoudi, Mehdi; Jamshidi, Ahmad Reza; Karami, Jafar; Mohseni, Alireza; Amirzargar, Ali Akbar; Farhadi, Elham; Ahmadzadeh, Nooshin; Nicknam, Mohammad Hossein

    2016-02-01

    Ankylosing Spondylitis (AS) is a chronic rheumatic disease which mainly involves the axial skeleton. It seems that non-HLA genes, as well as HLA-B27 gene, are linked to the etiology of the disease. Recently, it has been documented that KIRs and their HLA ligands are contributed to the Ankylosing Spondylitis. The aim of this study was to evaluate the KIR genes and their HLA ligands in Iranian AS patients and healthy individuals. The present study includes 200 AS patient samples and 200 healthy control samples. KIR genotyping was performed using the polymerase chain reaction sequence-specific primer (PCR-SSP) method to type the presence or absence of the 16 KIR genes, 6 known specific HLA class I ligands and also, two pseudogenes. Two KIR genes (KIR-2DL3 and KIR2DL5), and among the HLA ligands, two HLA ligands (HLA-C2Lys80 and HLA-B27) genes were significantly different between case and control groups. In addition, we found some interesting KIR/HLA compound genotypes, which were associated with AS susceptibility. Our results suggest that the AS patients present more activating and less inhibitory KIR genes with combination of their HLA ligands than healthy controls. Once the balance of signal transduction between activating and inhibitory receptors is disturbed, the ability of NK cells to identify and lyse the targets in immune responses will be compromised. Accordingly, imbalance of activating and inhibitory KIR genes by up-regulating the activation and losing the inhibition of KIRs signaling or combination of both might be one of the important factors which underlying the pathogenesis of AS.

  14. 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

    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

  15. 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

    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

  16. Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region.

    Jobe, Ousman; Trinh, Hung V; Kim, Jiae; Alsalmi, Wadad; Tovanabutra, Sodsai; Ehrenberg, Philip K; Peachman, Kristina K; Gao, Guofen; Thomas, Rasmi; Kim, Jerome H; Michael, Nelson L; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

    2016-06-01

    Monocytes and monocyte-derived macrophages express relatively low levels of CD4. Despite this, macrophages can be effectively infected with human immunodeficiency virus type 1. Macrophages have a critical role in human immunodeficiency virus type 1 transmission; however, the mechanism or mechanisms of virus infection are poorly understood. We report that growth factors, such as granulocyte macrophage colony-stimulating factor and macrophage colony-stimulating factor affect the phenotypic profile and permissiveness of macrophages to human immunodeficiency virus type 1. Human immunodeficiency virus type 1 infection of monocyte-derived macrophages derived from granulocyte macrophage and macrophage colony-stimulating factors was predominantly facilitated by the sialic acid-binding immunoglobulin-like lectin-1. The number of sialic acid-binding immunoglobulin-like lectin receptors on macrophage colony-stimulating factor-derived monocyte-derived macrophages was significantly greater than on granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages, and correspondingly, human immunodeficiency virus type 1 infection was greater in the macrophage colony-stimulating factor-derived monocyte-derived macrophages. Single-genome analysis and quantitative reverse transcriptase-polymerase chain reaction revealed that the differences in infectivity was not due to differences in viral fitness or in viral variants with differential infectivity but was due to reduced viral entry into the granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages. Anti-sialic acid-binding immunoglobulin-like lectin, trimeric glycoprotein 145, and scaffolded V1V2 proteins were bound to sialic acid-binding immunoglobulin-like lectin and significantly reduced human immunodeficiency virus type 1 entry and infection. Furthermore, sialic acid residues present in the V1V2 region of the envelope protein mediated human immunodeficiency virus type 1

  17. 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

    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

  18. 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

    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

  19. 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

    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

  20. 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

    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.

  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

    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. 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

    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...

  3. Raisin dietary fiber composition and in vitro bile acid binding.

    Camire, Mary E; Dougherty, Michael P

    2003-01-29

    Raisins are dried grapes that are popular shelf-stable snacks. Three commercially important types of raisins were studied: sun-dried (natural), artificially dried (dipped), and sulfur dioxide-treated (golden) raisins. Dietary fiber composition was analyzed by AACC method 32-25. Polysaccharides were hydrolyzed, and the resulting sugars were analyzed by colorimetric and gas chomatographic methods. Fructans were measured with a colorimetric kit assay. Total dietary fiber values agreed with published values, with pectins and neutral polysaccharides of mannose and glucose residues predominating. Dipped raisins had over 8% fructans. No fructans were found in fresh grapes. Raisin types varied in their ability to bind bile acids in vitro. Coarsely chopped raisins bound more bile than did finely chopped or whole raisins.

  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

    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

    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

    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. 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

    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

  8. 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

    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

  9. 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

    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.

  10. 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

    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.

  11. 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

    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.

  12. 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

    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.

  13. 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

    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.

  14. 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

    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.

  15. 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

    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

  16. 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

    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

  17. 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

    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

  18. 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

    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

  19. 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

    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

  20. Killer Immunoglobulin-Like Receptor Profiles are not Associated with risk of Amoxicillin-Clavulanate-Induced Liver Injury in Spanish Patients

    Camilla Stephens

    2016-08-01

    Full Text Available Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR that bind to human leukocyte antigen (HLA class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI is currently unknown. In this study we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC DILI patients in search for potential risk associations. 102 AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. 21.6% and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4% and 78.8%, respectively, contained at least one B haplotype (Bx. The genotypes translated into 27 (AC DILI and 46 (controls different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4 and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67% and 3DL1 + Bw4 motif (67%, while 2DL1 + epitope C2 (69% and 3DL1 + Bw4 motif (69% predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand associations in DILI, although our findings do not support evidence of these genetic variations playing a major role in AC DILI development.

  1. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein.

    Takahashi, K; Nakanishi, H; Miyahara, M; Mandai, K; Satoh, K; Satoh, A; Nishioka, H; Aoki, J; Nomoto, A; Mizoguchi, A; Takai, Y

    1999-05-03

    We have isolated a novel actin filament-binding protein, named afadin, localized at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell lines. Afadin has one PDZ domain, three proline-rich regions, and one actin filament-binding domain. We found here that afadin directly interacted with a family of the immunoglobulin superfamily, which was isolated originally as the poliovirus receptor-related protein (PRR) family consisting of PRR1 and -2, and has been identified recently to be the alphaherpes virus receptor. PRR has a COOH-terminal consensus motif to which the PDZ domain of afadin binds. PRR and afadin were colocalized at cadherin-based cell-cell AJs in various tissues and cell lines. In E-cadherin-expressing EL cells, PRR was recruited to cadherin-based cell-cell AJs through interaction with afadin. PRR showed Ca2+-independent cell-cell adhesion activity. These results indicate that PRR is a cell-cell adhesion molecule of the immunoglobulin superfamily which is recruited to cadherin-based cell-cell AJs through interaction with afadin. We rename PRR as nectin (taken from the Latin word "necto" meaning "to connect").

  2. Diversity of killer cell immunoglobulin-like receptor (KIR genotypes and KIR2DL2/3 variants in HCV treatment outcome.

    Jose Ramón Vidal-Castiñeira

    Full Text Available The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR (42.2% vs. 27.5%, p<0.05 and KIR2DL3*001 was associated with sustained viral response (SVR (41.6% vs. 61.2%, p<0.005. The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001. From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005 and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001. The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV was improved (from 55.9% to 75.3% when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.

  3. Analysis of the Expression and Function of Immunoglobulin-Like Transcript 4 (ILT4, LILRB2 in Dendritic Cells from Patients with Systemic Lupus Erythematosus

    Paola del Carmen Guerra-de Blas

    2016-01-01

    Full Text Available Dendritic cells (DC play an important role in the development and maintenance of immune tolerance. Although the inhibitory receptor ILT4/LILRB2 has been related with the tolerogenic phenotype of DC, the possible role of this receptor in the breakdown of DC tolerogenic function in systemic lupus erythematosus (SLE has not been elucidated. In this study, we analyzed the expression and function of the inhibitory receptor ILT4 in DC from SLE patients. We found that the percentage of ILT4 positive plasmacytoid DC and myeloid DC is significantly diminished in SLE patients. Interestingly, ligation of ILT4 did not affect the maturation or immunogenic capability of DC in healthy controls. In contrast, in SLE patients we observed an inhibitory effect of ILT4 on the immunogenic capability of DC. ILT4 was shown not to have a crucial role in regulating the maturation and function of DC from healthy controls but is partially involved in the maturation process and immunogenic capability of DC from SLE patients, suggesting that other inhibitory receptors, involved in the regulation of DC tolerogenic function, may be impaired in this autoimmune disease.

  4. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate–Induced Liver Injury in Spanish Patients

    Stephens, Camilla; Moreno-Casares, Antonia; López-Nevot, Miguel-Ángel; García-Cortés, Miren; Medina-Cáliz, Inmaculada; Hallal, Hacibe; Soriano, German; Roman, Eva; Ruiz-Cabello, Francisco; Romero-Gomez, Manuel; Lucena, M. Isabel; Andrade, Raúl J.

    2016-01-01

    Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand associations in DILI, although our findings do not support evidence of these genetic variations playing a major role in AC DILI development. PMID:27616993

  5. Analysis of the Expression and Function of Immunoglobulin-Like Transcript 4 (ILT4, LILRB2) in Dendritic Cells from Patients with Systemic Lupus Erythematosus

    Guerra-de Blas, Paola del Carmen; Villaseñor-Talavera, Yael Sebastián; Cruz-González, Daniela de Jesús; Baranda, Lourdes; Doníz-Padilla, Lesly; Abud-Mendoza, Carlos; González-Amaro, Roberto; Monsiváis-Urenda, Adriana Elizabeth

    2016-01-01

    Dendritic cells (DC) play an important role in the development and maintenance of immune tolerance. Although the inhibitory receptor ILT4/LILRB2 has been related with the tolerogenic phenotype of DC, the possible role of this receptor in the breakdown of DC tolerogenic function in systemic lupus erythematosus (SLE) has not been elucidated. In this study, we analyzed the expression and function of the inhibitory receptor ILT4 in DC from SLE patients. We found that the percentage of ILT4 positive plasmacytoid DC and myeloid DC is significantly diminished in SLE patients. Interestingly, ligation of ILT4 did not affect the maturation or immunogenic capability of DC in healthy controls. In contrast, in SLE patients we observed an inhibitory effect of ILT4 on the immunogenic capability of DC. ILT4 was shown not to have a crucial role in regulating the maturation and function of DC from healthy controls but is partially involved in the maturation process and immunogenic capability of DC from SLE patients, suggesting that other inhibitory receptors, involved in the regulation of DC tolerogenic function, may be impaired in this autoimmune disease. PMID:27057555

  6. The structure of a purple acid phosphatase involved in plant growth and pathogen defence exhibits a novel immunoglobulin-like fold

    Svetlana Vladimirovna Antonyuk

    2014-03-01

    Full Text Available Phosphatases function in the production, transport and recycling of inorganic phosphorus, which is crucial for cellular metabolism and bioenergetics, as well as in bacterial killing, since they are able to generate reactive oxygen species via Fenton chemistry. Diphosphonucleotide phosphatase/phosphodiesterase (PPD1, a glycoprotein plant purple acid phosphatase (PAP from yellow lupin seeds, contains a bimetallic Fe–Mn catalytic site which is most active at acidic pH. Unlike other plant PAPs, PPD1 cleaves the pyrophosphate bond in diphosphonucleotides and the phosphodiester bond in various phosphodiesters. The homohexameric organization of PPD1, as revealed by a 1.65 Å resolution crystal structure and confirmed by solution X-ray scattering, is unique among plant PAPs, for which only homodimers have previously been reported. A phosphate anion is bound in a bidentate fashion at the active site, bridging the Fe and Mn atoms in a binding mode similar to that previously reported for sweet potato PAP, which suggests that common features occur in their catalytic mechanisms. The N-terminal domain of PPD1 has an unexpected and unique fibronectin type III-like fold that is absent in other plant PAPs. Here, the in vitro DNA-cleavage activity of PPD1 is demonstrated and it is proposed that the fibronectin III-like domain, which `overhangs' the active site, is involved in DNA selectivity, binding and activation. The degradation of DNA by PPD1 implies a role for PPD1 in plant growth and repair and in pathogen defence.

  7. 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

    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%,

  8. 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

    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

  9. 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

    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

  10. 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

    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)

  11. 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

    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

  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

    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

    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

    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

    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

    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

    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

    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. 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

    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

  20. 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

    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

  1. 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

    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

  2. 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

    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

  3. 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

    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

  4. 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

    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

  5. 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

    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

  6. 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

    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

  7. 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

    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

  8. 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

    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

  9. 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

    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

  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

    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. 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

    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

  12. 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

    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

  13. 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

    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

  14. 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

    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

  15. 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

    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

  16. 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

    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.

  17. 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

    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

  18. 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

    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

  19. 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

    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

  20. In vitro RNase and nucleic acid binding activities implicate coilin in U snRNA processing.

    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.

  1. Effect of nucleic acid binding dyes on DNA extraction, amplification, and STR typing.

    Haines, Alicia M; Tobe, Shanan S; Kobus, Hilton J; Linacre, Adrian

    2015-10-01

    We report on the effects of six dyes used in the detection of DNA on the process of DNA extraction, amplification, and detection of STR loci. While dyes can be used to detect the presence of DNA, their use is restricted if they adversely affect subsequent DNA typing processes. Diamond™ Nucleic Acid Dye, GelGreen™, GelRed™, RedSafe™, SYBR(®) Green I, and EvaGreen™ were evaluated in this study. The percentage of dye removed during the extraction process was determined to be: 70.3% for SYBR(®) Green I; 99.6% for RedSafe™; 99.4% for EvaGreen™; 52.7% for Diamond™ Dye; 50.6% for GelRed™, and; could not be determined for GelGreen™. It was then assumed that the amount of dye in the fluorescent quantification assay had no effect on the DNA signal. The presence of all six dyes was then reviewed for their effect on DNA extraction. The t-test showed no significant difference between the dyes and the control. These extracts were then STR profiled and all dyes and control produced full DNA profiles. STR loci in the presence of GelGreen(TM) at 1X concentration showed increased amplification products in comparison to the control samples. Full STR profiles were detected in the presence of EvaGreen™ (1X), although with reduced amplification products. RedSafe™ (1X), Diamond™ Dye (1X), and SYBR(®) Green I (1X) all exhibited varying degrees of locus drop-out with GelRed™ generating no loci at all. We provide recommendations for the best dye to visualize the presence of DNA profile as a biological stain and its subsequent amplification and detection.

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

    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.

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

    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.

  4. Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays

    Mukherjee, Sourav; Alicia M Hanson; Shadrick, William R.; Ndjomou, Jean; Sweeney, Noreena L.; Hernandez, John J.; Bartczak, Diana; Li, Kelin; Frankowski, Kevin J.; Heck, Julie A.; Arnold, Leggy A.; Schoenen, Frank J.; Frick, David N.

    2012-01-01

    Typical assays used to discover and analyze small molecules that inhibit the hepatitis C virus (HCV) NS3 helicase yield few hits and are often confounded by compound interference. Oligonucleotide binding assays are examined here as an alternative. After comparing fluorescence polarization (FP), homogeneous time-resolved fluorescence (HTRF®; Cisbio) and AlphaScreen® (Perkin Elmer) assays, an FP-based assay was chosen to screen Sigma’s Library of Pharmacologically Active Compounds (LOPAC) for c...

  5. Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays.

    Mukherjee, Sourav; Hanson, Alicia M; Shadrick, William R; Ndjomou, Jean; Sweeney, Noreena L; Hernandez, John J; Bartczak, Diana; Li, Kelin; Frankowski, Kevin J; Heck, Julie A; Arnold, Leggy A; Schoenen, Frank J; Frick, David N

    2012-09-01

    Typical assays used to discover and analyze small molecules that inhibit the hepatitis C virus (HCV) NS3 helicase yield few hits and are often confounded by compound interference. Oligonucleotide binding assays are examined here as an alternative. After comparing fluorescence polarization (FP), homogeneous time-resolved fluorescence (HTRF®; Cisbio) and AlphaScreen® (Perkin Elmer) assays, an FP-based assay was chosen to screen Sigma's Library of Pharmacologically Active Compounds (LOPAC) for compounds that inhibit NS3-DNA complex formation. Four LOPAC compounds inhibited the FP-based assay: aurintricarboxylic acid (ATA) (IC50=1.4 μM), suramin sodium salt (IC50=3.6 μM), NF 023 hydrate (IC50=6.2 μM) and tyrphostin AG 538 (IC50=3.6 μM). All but AG 538 inhibited helicase-catalyzed strand separation, and all but NF 023 inhibited replication of subgenomic HCV replicons. A counterscreen using Escherichia coli single-stranded DNA binding protein (SSB) revealed that none of the new HCV helicase inhibitors were specific for NS3h. However, when the SSB-based assay was used to analyze derivatives of another non-specific helicase inhibitor, the main component of the dye primuline, it revealed that some primuline derivatives (e.g. PubChem CID50930730) are up to 30-fold more specific for HCV NS3h than similarly potent HCV helicase inhibitors.

  6. Hyaluronic acid binding, endocytosis and degradation by sinusoidal liver endothelial cells

    McGary, C.T.

    1988-01-01

    The binding, endocytosis, and degradation of {sup 125}I-hyaluronic acid ({sup 125}I-HA) by liver endothelial cells (LEC) was studied under several conditions. The dissociation of receptor-bound {sup 125}I-HA was rapid, with a half time of {approx}31 min and a K{sub off} of 6.3 {times} 10{sup {minus}4}/sec. A large reversible increase in {sup 125}I-HA binding to LEC at pH 5.0 was due to an increase in the observed affinity of the binding interaction. Pronase digestion suggested the protein nature of the receptor and the intracellular location of the digitonin exposed binding activity. Binding and endocytosis occur in the presence of 10 mM EGTA indicating that divalent cations are not required for receptor function. To study the degradation of {sup 125}I-HA by LEC, a cetylpyridinium chloride (CPC) precipitation assay was characterized. The minimum HA length required for precipitation was elucidated. The fate of the LEC HA receptor after endocytosis was examined.

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

    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 of lipids and retinol. CONCLUSIONS/SIGNIFICANCE: The divergent biochemical properties, physiological roles and cellular distributions of the TsMFABPs might be one of the critical mechanisms compensating for inadequate de novo FA synthesis. These proteins might exert harmonized or independent roles on lipid assimilation and intracellular signaling. The specialized distribution of retinol in the canal region further implies that cells in this region might differentiate into diverse cell types during metamorphosis into an adult worm. Identification of bioactive systems pertinent to parasitic homeostasis may provide a valuable target for function-related drug design.

  8. Correlation study between sperm concentration, hyaluronic acid-binding capacity and sperm aneuploidy in Hungarian patients.

    Mokánszki, Attila; Molnár, Zsuzsanna; Ujfalusi, Anikó; Balogh, Erzsébet; Bazsáné, Zsuzsa Kassai; Varga, Attila; Jakab, Attila; Oláh, Éva

    2012-12-01

    Infertile men with low sperm concentration and/or less motile spermatozoa have an increased risk of producing aneuploid spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding may reduce genetic risks such as chromosomal rearrangements and numerical aberrations. Fluorescence in-situ hybridization (FISH) has been used to evaluate the presence of aneuploidies. This study examined spermatozoa of 10 oligozoospermic, 9 asthenozoospermic, 9 oligoasthenozoospermic and 17 normozoospermic men by HA binding and FISH. Mean percentage of HA-bound spermatozoa in the normozoospermic group was 81%, which was significantly higher than in the oligozoospermic (Psex chromosomes (P=0.014) and chromosome 17 (P=0.0019), diploidy (P=0.03) and estimated numerical chromosome aberrations (P=0.004) were significantly higher in the oligoasthenozoospermic group compared with the other groups. There were statistically significant relationships (Pchromosome aberrations (r=-0.668) and between HA binding and estimated numerical chromosome aberrations (r=-0.682). HA binding and aneuploidy studies of spermatozoa in individual cases allow prediction of reproductive prognosis and provision of appropriate genetic counselling. Infertile men with normal karyotypes and low sperm concentrations and/or less motile spermatozoa have significantly increased risks of producing aneuploid (diminished mature) spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding, based on a binding between sperm receptors for zona pellucida and HA, may reduce the potential genetic risks such as chromosomal rearrangements and numerical aberrations. In the present study we examined sperm samples of 45 men with different sperm parameters by HA-binding assay and fluorescence in-situ hybridization (FISH). Mean percentage of HA-bound spermatozoa in the normozoospermic group was significantly higher than the oligozoospermic, the asthenozoospermic and the oligoasthenozoospermic groups. Using FISH, disomy of sex chromosomes and chromosome 17, diploidy and estimated numerical chromosome aberration frequencies were significantly higher in the oligoasthenozoospermic group compared with the three other groups. A significant positive correlation was found between the sperm concentration and the HA-binding capacity, and significant negative correlations between the sperm concentration and the estimated numerical chromosomes aberrations as well as between the HA-binding ability and the estimated numerical chromosome aberrations were identified. We conclude that HA-binding assay and sperm aneuploidy study using FISH may help to predict the reproductive ability of selected infertile male patients and to provide appropriate genetic counselling.

  9. Role of Fatty Acid Binding Protein 5 (FABP5) in Breast Cancer Progression and Metastasis

    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

  10. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.

    Jay, Anthony G; Chen, Alexander N; Paz, Miguel A; Hung, Justin P; Hamilton, James A

    2015-02-20

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes.

  11. In Vitro Bile-Acid-Binding of Whole vs. Pearled Wheat Grain

    Health benefits of consuming whole grains help reduce the risk of heart disease, stroke and cancer. The USDA Food Guide pyramid and dietary guidelines recommend the consumption of 6-10 oz of grain products daily and one-half of that is desired to be containing whole grains (2005). Whole grains con...

  12. Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias.

    1990-01-01

    Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the nu...

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

    Zahid, Henna; Miah, Layeque; Lau, Andy; Brochard, Lea; Hati, Debolina; Bui, T. T.; Drake, A. 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 investigate...

  14. Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies

    Kaur R

    2012-07-01

    Full Text Available Randeep Kaur,1 Jackson M Chitanda,2 Deborah Michel,1 Jason Maley,3 Ferenc Borondics,2,4 Peng Yang,5 Ronald E Verrall,2 Ildiko Badea11Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 2Department of Chemistry, University of Saskatchewan, 3Saskatchewan Structural Sciences Centre, University of Saskatchewan, 4Canadian Light Source, University of Saskatchewan, Saskatoon, SK, Canada; 5Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, People's Republic of ChinaPurpose: Detonation nanodiamonds (NDs are carbon-based nanomaterials that, because of their size (4–5 nm, stable inert core, alterable surface chemistry, fluorescence, and biocompatibility, are emerging as bioimaging agents and promising tools for the delivery of biochemical molecules into cellular systems. However, diamond particles possess a strong propensity to aggregate in liquid formulation media, restricting their applicability in biomedical sciences. Here, the authors describe the covalent functionalization of NDs with lysine in an attempt to develop nanoparticles able to act as suitable nonviral vectors for transferring genetic materials across cellular membranes.Methods: NDs were oxidized and functionalized by binding lysine moieties attached to a three-carbon-length linker (1,3-diaminopropane to their surfaces through amide bonds. Raman and Fourier transform infrared spectroscopy, zeta potential measurement, dynamic light scattering, atomic force microscopic imaging, and thermogravimetric analysis were used to characterize the lysine-functionalized NDs. Finally, the ability of the functionalized diamonds to bind plasmid DNA and small interfering RNA was investigated by gel electrophoresis assay and through size and zeta potential measurements.Results: NDs were successfully functionalized with the lysine linker, producing surface loading of 1.7 mmol g-1 of ND. These modified NDs formed highly stable aqueous dispersions with a zeta potential of 49 mV and particle size of approximately 20 nm. The functionalized NDs were found to be able to bind plasmid DNA and small interfering RNA by forming nanosized "diamoplexes".Conclusion: The lysine-substituted ND particles generated in this study exhibit stable aqueous formulations and show potential for use as carriers for genetic materials.Keywords: disaggregation, spectroscopy, dispersion, electrophoresis, size, zeta potential

  15. A glucuronic acid binding leguminous lectin with mitogenic activity toward mouse splenocytes.

    Chan, Yau Sang; Wong, Jack Ho; Ng, Tzi Bun

    2011-02-01

    A dimeric 64-kDa lectin was purified from seeds of French bean (Phaseolus vulgaris) cultivar number 1. The purification protocol entailed Q-Sepharose, Affi-gel blue gel, Mono S and Superdex 75. The lectin-enriched fraction was adsorbed on Q-Sepharose and Affi-gel blue gel and desorbed using 1M NaCl in the starting buffer. Hemagglutinating activity was adsorbed on Mono S and eluted with a linear 0.3-1 M NaCl gradient. Gel filtration on Superdex 75 yielded a single absorbance peak which appeared as a single 32-kDa in sodium dodecyl sulfate poylacylamide gel electrophoresis. Full hemagglutinating activity was observed when the lectin was exposed to a pH ranging from 3 to 11. About 50% activity remained at pH 12, and about 25% at pH 0 to pH 2. Activity was totally abolished at pH 13-14. The activity was completely preserved when the ambient temperature was 20 °C-60 °C. However, only 50% and 12.5% of the activity remained at 65 °C and 70 °C, respectively. Activity was barely discernible at 75 °C and completely abrogated at and above 80 °C. Hemagglutinating activity of the lectin was inhibited by glucuronic acid. Maximum mitogenic activity of the lectin toward murine splenocytes occurred at a lectin concentration of 0.488 µM. The mitogenic activity was nearly eliminated in the presence of 250 mM glucuronic acid. The lectin did not exhibit antiproliferative activity toward hepatoma (HepG2) cells, breast cancer (MCF7) cells, and nasopharynegeal carcinoma CNE stage 1 and stage 2 cells. It was also devoid of significant anti-HIV reverse transcriptase activity.

  16. Influence of the conserved disulphide bond, exposed to the putative binding pocket, on the structure and function of the immunoglobulin-like molecular chaperone Caf1M of Yersinia pestis.

    Zav'yalov, V P; Chernovskaya, T V; Chapman, D A; Karlyshev, A V; MacIntyre, S; Zavialov, A V; Vasiliev, A M; Denesyuk, A I; Zav'yalova, G A; Dudich, I V; Korpela, T; Abramov, V M

    1997-06-01

    The Yersinia pestis protein Caf1M is a typical representative of a subfamily of periplasmic molecular chaperones with characteristic structural and functional features, one of which is the location of two conserved cysteine residues close to the putative binding pocket. We show that these residues form a disulphide bond, the reduction and alkylation of which significantly increases the dissociation constant of the Caf1M-Caf1 (where Caf 1 is a polypeptide subunit of the capsule) complex [from a Kd of (4.77+/-0.50)x10(-9) M for the intact protein to one of (3.68+/-0.68)x10(-8) M for the modified protein]. The importance of the disulphide bond for the formation of functional Caf1M in vivo was demonstrated using an Escherichia coli dsbA mutant carrying the Y. pestis f1 operon. In accordance with the CD and fluorescence measurements, the disulphide bond is not important for maintenance of the overall structure of the Caf1M molecule, but would appear to affect the fine structural properties of the subunit binding site. A three-dimensional model of the Caf1M-Caf1 complex was designed based on the published crystal structure of PapD (a chaperone required for Pap pili assembly) complexed with a peptide corresponding to the C-terminus of the papG subunit. In the model the disulphide bond is in close proximity to the invariant Caf1M Arg-23 and Lys-142 residues that are assumed to anchor the C-terminal group of the subunit. The importance of this characteristic disulphide bond for the orchestration of the binding site and subunit binding, as well as for the folding of the protein in vivo, is likely to be a common feature of this subfamily of Caf1M-like chaperones. A possible model for the role of the disulphide bond in Caf1 assembly is discussed.

  17. 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

    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...

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

    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.

  19. No difference in high-magnification morphology and hyaluronic acid binding in the selection of euploid spermatozoa with intact DNA

    Suchada Mongkolchaipak; Teraporn Vutyavanich

    2013-01-01

    In this study,we compared conventional sperm selection with high-magnification morphology based on the motile sperm organellar morphology examination (MSOME) criteria,and hyaluronic acid (HA) binding for sperm chromosome aneuploidy and DNA fragmentation rates.Semen from 50 severe male factor cases was processed through density gradient centrifugation,and subjected to sperm selection by using the conventional method (control),high magnification at x 6650 or HA binding.Aneuploidy was detected by fluorescence in situ hybridization with probes for chromosomes 13,18,21,X and Y,and DNA fragmentation by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) method.Spermatozoa selected under high-magnification had a lower DNA fragmentation rate (2.6% vs.1.7%; P=0.032),with no significant difference in aneuploidy rate (0.8% vs 0.7%; P=0.583),than those selected by the HA binding method.Spermatozoa selected by both methods had much lower aneuploidy and DNA fragmentation rate than the controls (7% aneuploidy and 26.8% DNA fragmentation rates,respectively).In the high-magnification group,the aneuploidy rate was lower when the best spermatozoa were selected than when only the second-best spermatozoa were available for selection,but the DNA fragmentation rate was not different.In conclusion,sperm selection under high magnification was more effective than under HA binding in selecting spermatozoa with low DNA fragmentation rate,but the small difference (0.9%) might not be clinically meaningful.Both methods were better than the conventional method of sperm selection.

  20. Tannic acid binding of cell surfaces in normal, premalignant, and malignant squamous epithelium of the human uterine cervix.

    Davina, J H; Lamers, G E; van Haelst, U J; Kenemans, P; Stadhouders, A M

    1984-01-01

    Alterations in tannic acid (TA) binding capacity of cell surface carbohydrates in normal, premalignant, and malignant squamous epithelium of the human uterine cervix have been studied using electron microscopic visualization in combination with microdensitometric evaluation. While in normal epithelium there is distinct binding in four to five cell layers of the deep intermediate zone, cells of carcinoma in situ and invasive cancer lesions lack TA binding. In moderate dysplasia an intermediate reacting pattern is found. Deep intermediate cells in areas bordering the carcinoma in situ lesions do not show any binding, although their ultrastructure cannot be distinguished from similar cells in normal tissue. The TA deposition within the deep intermediate zone is probably related to the presence here of glycoprotein-containing membrane-coating granules. The finding that TA binding discriminates between cells in normal squamous epithelium and morphologically normal cells in juxtaposition with lesional areas in premalignant and malignant epithelium opens the possibility for a more reliable cytologic diagnosis of cervical epithelial neoplasia.

  1. Deoxyribonucleic acid-binding ability of androgen receptors in whole cells: implications for the actions of androgens and antiandrogens

    C.W. Kuil (Cor); E. Mulder (Eppo)

    1996-01-01

    textabstractIn whole cells, the effects of several androgens and antiandrogens on the in the induction of DNA binding for the human wild-type androgen receptor (AR) and a mutant receptor ARL (LNCaP mutation; codon 868, Thr to Ala) were examined and related to the transc

  2. Clinical study on intestinal fatty acid binding protein and the endotoxin in early diagnosis of intestinal barrier dysfunction

    孔令尚

    2013-01-01

    Objective To screen the high specific and sensitivemonitoring indications in the diagnosis of intestinal barrier dysfunction.Methods A total of 70 critical patients with intestinal barrier dysfunction and acute physiology

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

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

    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.

  5. α-Cyclodextrin/aminobenzoic acid binding in salt solutions at different pH: dependence on guest structure.

    Romanova, Anastasia; Chibunova, Ekaterina; Kumeev, Roman; Fedorov, Maxim; Terekhova, Irina

    2013-06-01

    Influence of Na(+) and K(+) cations on α-cyclodextrin guest-host complex formation with isomeric aminobenzoic acids was examined at different pH and temperature of 298.15 K by (1)H NMR and calorimetry methods. More pronounced influence of Na(+) on inclusion complex formation of α-CD with aminobenzoic acid anions compare to the effects of Na(+) on α-CD complex formation with zwitterionic aminobenzoic acid molecules was revealed. For the first time, the dependence of salt effects on the structure, ionization and the hydration state of the guest molecule was demonstrated and analysed on the basis of the obtained thermodynamic parameters of complex formation and calculated free energy of hydration of different ionized forms of aminobenzoic acids.

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

    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...

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

    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.

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

    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.

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

    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.

  10. Diverse CdII coordination complexes derived from bromide isophthalic acid binding with auxiliary N-donor ligands

    Tang, Meng; Dong, Bao-Xia; Wu, Yi-Chen; Yang, Fang; Liu, Wen-Long; Teng, Yun-Lei

    2016-12-01

    The coordination characteristics of 4-bromoisophthalic acid (4-Br-H2ip) have been investigated in a series of CdII-based frameworks. Hydrothermal reactions of CdII salts and 4-Br-H2ip together with flexible or semiflexible N-donor auxiliary ligands resulted in the formation of four three-dimensional coordination complexes with diverse structures: {Cd(bix)0.5(bix)0.5(4-Br-ip)]·H2O}n (1), [Cd(bbi)0.5(bbi)0.5(4-Br-ip)]n (2), {[Cd(btx)0.5(4-Br-ip)(H2O)]·0.5CH3OH·H2O}n (3) and {[Cd(bbt)0.5(4-Br-ip)(H2O)]·3·5H2O}n (4). These compounds were characterized by elemental analyses, IR spectra, single-crystal and powder X-ray diffraction. They displayed diverse structures depending on the configuration of the 4-connected metal node, the coordination mode of the 4-Br-H2ip, the coordination ability and conformationally flexibility of the N-donor auxiliary. Compound 1 exhibits 3-fold interpenetrated 66 topology and compound 2 has a 412 topology. Compounds 3-4 have similar 3D pillar-layered structures based on 3,4-connected binodal net with the Schläfli symbol of (4·38). The thermal stabilities and photoluminescence properties of them were discussed in detail.

  11. Effects of neonatal. gamma. -ray irradiation on rat hippocampus: Pt. 2; Development of excitatory amino acid binding sites

    Dessi, F.; Represa, A.; Ben-Ari, Y. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France))

    1991-01-01

    In the rat, neonatal irradiation produces a destruction of denate granule cells and prevents the development of the mossy fibre-CA3 pyramidal cell synapse. The developmental increase of high affinity kainate binding sites in the stratum lucidum was reduced on the irradiated side as compared with the control side. This suggests that a proportion of high affinity kainate binding sites is associated with mossy fibres. In contrast, the development profile of N-methyl-D-aspartate binding sites, which are associated with associational and commissural synapses in CA3, was not affected by irradiation. The role that afferent fibres may play in the development of pyramidal cells is discussed in connection with the modulatory effects of glutamate receptors on the development of neurons. (author).

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

    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.

  13. Increased Hyaluronan Acid Binding Ability of Spermatozoa Indicating a Better Maturity, Morphology, and Higher DNA Integrity After Micronutrient Supplementation

    Markus Lipovac

    2014-05-01

    Full Text Available Measuring the hyaluronan-binding ability of spermatozoa is useful in predicting the ability of spermatozoa to fertilise oocytes during in vitro fertilisation (IVF. Recent publications discuss an influence of micronutrients on sperm quality. The objective of this paper was to evaluate the effect of a non-prescription nutraceutical containing eight micronutrients on sperm-hyaluronan binding assay (SHBA values among males with idiopathic sub-/infertility, using an open comparative pilot study. The study took place at the Outpatient Fertility Centre IMI, Vienna, Austria, and involved 67 sub-/infertile males. Sub-/infertile males were invited to participate and take two daily capsules of the active compound for a 3-month period between the first and the follow-up semen analysis. Each capsule contained L-carnitine, L-arginine, zinc, vitamin E, glutathione, selenium, coenzyme Q10 (CoQ10, and folic acid (Profertil®. 40 sub-/infertile men receiving no active treatment served as controls; this was measured by change in SHBA after 3 months. It was found that SHBA values significantly increased after 3 months of treatment with the active compound, from a median baseline value of 56.0% to 74% (p<0.05. This represented a 19.7% increase compared to baseline, which was significantly higher than the 2.1% decrease observed in the control group. The rate of subjects displaying an increase in SHBA values after 3 months was significantly higher in the active group (74.6% versus 30.0%, p=0.0001, which showed that sub-/infertile men treated with the active micronutrient compound displayed increased SHBA ability. However, more research is necessary to get detailed information on this specific subject.

  14. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases.

    Phongsisay, Vongsavanh

    2016-04-01

    The Gram-negative bacterium Campylobacter jejuni causes gastroenteritis and Guillain-Barré syndrome in humans. Recent advances in the immunobiology of C. jejuni have been made. This review summarizes C. jejuni-binding innate receptors and highlights the role of innate immunity in autoimmune diseases. This human pathogen produces a variety of glycoconjugates, including human ganglioside-like determinants and multiple activators of Toll-like receptors (TLRs). Furthermore, C. jejuni targets MyD88, NLRP3 inflammasome, TIR-domain-containing adapter-inducing interferon-β (TRIF), sialic acid-binding immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied. MyD88-mediated TLR activation or inflammasome-dependent IL-1β secretion is essential for autoimmune induction. TRIF mediates the production of type I interferons that promote humoral immune responses and immunoglobulin class-switching. Siglec-1 and Siglec-7 interact directly with gangliosides. Siglec-1 activation enhances phagocytosis and inflammatory responses. MGL internalizes GalNAc-containing glycoconjugates. TREM2 is well-known for its role in phagocytosis. LMIR5 recognizes C. jejuni components and endogenous sulfoglycolipids. Several lines of evidence from animal models of autoimmune diseases suggest that simultaneous activation of innate immunity in the presence of autoreactive lymphocytes or antigen mimicry may link C. jejuni to immunopathology.

  15. Siglec-1 and -2 as potential biomarkers in autoimmune disease.

    Eakin, Amanda J; Bustard, Michael J; McGeough, Cathy M; Ahmed, Tahanver; Bjourson, Anthony J; Gibson, David S

    2016-06-01

    Autoimmune diseases (ADs) are currently treated with anti-inflammatory and immunosuppressive drugs, aimed at reducing symptoms of disease in order to improve quality of life for patients. However, for a significant number of patients these therapies are ineffective, leading to an increased risk of irreversible damage and eventual disability in certain cases. Growing evidence has implicated glycosylated proteins and their cognate receptors in modulation of the autoimmune response. This review will summarize these findings with particular focus on sialic acid-binding immunoglobulin-like lectin (Siglec)-1 and Siglec-2 involvement in AD. Fluctuations in these glycosylation-dependent pathways could act as sentinels of disease activity or drug responses. If validated, protein modification and cellular response markers could help clinicians achieve remission earlier.

  16. Siglec-F is a novel intestinal M cell marker.

    Gicheva, Nadezhda; Macauley, Matthew S; Arlian, Britni M; Paulson, James C; Kawasaki, Norihito

    2016-10-07

    Intestinal microfold (M) cells are epithelial cells primarily present on Peyer's patches (PPs) in the small intestine. The ability of M cells to shuttle antigens into the PP for appropriate immune responses makes M cells a target for next-generation oral vaccine delivery. In this regard, discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery of cargo to M cells. Here, using a monoclonal antibody we generated to the Sialic acid-binding immunoglobulin-like lectin F (Siglec-F), we show that Siglec-F is expressed on mouse M cells in the small intestine. Immunohistochemical analysis of the PP tissue sections shows that Siglec-F is expressed on the surface of the M cell membrane exposed to the intestinal lumen. Anti-Siglec-F antibody injected into the mouse small intestine bound to M cells, demonstrating the potential to target M cells via Siglec-F.

  17. Analysis on the correlation between killer immunoglobulin-like receptor gene polymorphism and cervical cancer%杀伤细胞免疫球蛋白样受体基因多态性与宫颈癌的相关性分析

    许联红; 戚传平; 王永仿; 蒋立新

    2013-01-01

    目的 探讨杀伤细胞免疫球蛋白(Ig)样受体(KIR)基因多态性与宫颈癌的相关性.方法 收集167例宫颈上皮内瘤变3级(CIN3)/宫颈癌患者和163例年龄匹配的无血缘关系健康女性外周血标本.采用SYBR Green Ⅰ实时荧光PCR分析KIR基因及基因型频率在两组人群间的差异.结果 CIN3/宫颈癌组的KIR2DL2和2DS2基因频率低于健康人对照组(10.2% vs28.8%,P=0.000; 9.6% vs 25.2%,P=0.000).KIR2DL2/2DS2共表达个体的频率在病例组低于健康人对照组(9.0% vs22.7%,P=0.001),与降低疾病的患病风险有关(OR =0.336).基因型AA1和BX8与增加CIN3/宫颈癌的患病风险有关(49.1% vs 35.6%,OR=1.746,P=0.013;10.8% vs 4.3%,OR=2.692,P=0.026),而BX4与降低疾病的患病风险有关(2.4% vs 7.4%,OR =0.309,P=0.036).结论 KIR2DL2/2DS2对宫颈癌的发生可能具有保护性作用.

  18. Sialic acid is required for neuronal inhibition by soluble MAG but not for membrane bound MAG

    Najat eAl-Bashir

    2016-04-01

    Full Text Available Myelin-Associated Glycoprotein (MAG, a major inhibitor of axonal growth, is a member of the immunoglobulin (Ig super-family. Importantly, MAG (also known as Siglec-4 is a member of the Siglec family of proteins (sialic acid-binding, immunoglobulin-like lectins, MAG binds to complex gangliosides, specifically GD1a and/or GT1b. Therefore, it has been proposed as neuronal receptors for MAG inhibitory effect of axonal growth. Previously, we showed that MAG binds sialic acid through domain 1 at Arg118 and is able to inhibit axonal growth through domain 5.We developed a neurite outgrowth assay (NOG, in which both wild type MAG and mutated MAG (MAG Arg118 are expressed on cells. In addition we also developed a soluble form NOG in which we utilized soluble MAG-Fc and mutated MAG (Arg118-Fc. Only MAG-Fc is able to inhibit neurite outgrowth, but not mutated MAG (Arg118-Fc that has been mutated at its sialic acid binding site. However, both forms of membrane bound MAG- and MAG (Arg118- expressing cells still inhibit neurite outgrowth. Here, we review various results from different groups regarding MAG’s inhibition of axonal growth. Also, we propose a model in which the sialic acid binding is not necessary for the inhibition induced by the membrane form of MAG, but it is necessary for the soluble form of MAG. This finding highlights the importance of understanding the different mechanisms by which MAG inhibits neurite outgrowth in both the soluble fragmented form and the membrane-bound form in myelin debris following CNS damage

  19. In vitro bile acid-binding capacity of dietary fibre sources and their effects with bile acid on broiler chicken performance and lipid digestibility.

    Hemati Matin, H R; Shariatmadari, F; Karimi Torshizi, M A; Chiba, L I

    2016-06-01

    A 4 × 2 factorial experiment was conducted to study the effect of feeding diets-containing dietary fibre (DF) sources and a source of bile acid (BA) on growth performance and lipid metabolism. In addition, in vitro BA-binding capacity of fibre sources was investigated. A total of 256 one-d-old male broiler chickens (Ross 308) were assigned to DF sources [maize-soybean meal (control, C), or 30 g/kg of wheat bran (WB), barley bran (BB) or soybean hulls (SH)] and BA (with or without 1.5 g Na-deoxycholate/kg). Each treatment was replicated 4 times with 8 broiler chickens per cage. The highest in vitro BA-binding capacity was observed with BB (8.76 mg/g BB). From 0 to 21 d, with the addition of BA, the average daily feed intake (ADFI) decreased in broiler chickens fed on the C, WB or BB diets, while there was no difference with the SH diet. With added BA, the average daily gain decreased in broiler chickens fed on the C or SH diets, but it did not change in those fed on the other diets. The addition of BA decreased feed conversion ratio (FCR) in broiler chickens fed on the BB or WB diets, but it increased in those fed on the C or SH diets. Interaction results indicated that the apparent ileal digestibility of lipid increased in broiler chickens fed the C and other DF diets with BA compared to those fed the diets without BA. The addition of BA decreased the pancreas lipase activity (PLA) in broiler chickens fed on the C diet compared to those fed the C diet without BA, while no changes observed in those fed the DF diets with or without BA. No interaction was observed in total liver bile acid (TLBA). The WB, BB and SH with little Na-deoxycholate-binding capacity (chickens. The magnitude of improvement in digestibility of lipid with the addition of BA depends on the source of fibre used and the addition of BA in DF diets had little effect on growth performance in young broiler chicken diets.

  20. Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid-binding protein content in liver, heart and kidney of the diabetic rat

    Engels, W; van Bilsen, M; Wolffenbuttel, B H; van der Vusse, G J; Glatz, J F

    1999-01-01

    Diabetes mellitus generally results in an increased systemic fatty acid mobilization which can be associated with an increase in mitochondrial and peroxisomal beta-oxidation of fatty acids in selected tissues. The latter is usually accompanied by a concomitant increase in the tissue content of cytop

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

    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

  2. Ala54Thr fatty acid-binding protein 2 (FABP2) polymorphism in recurrent depression : associations with fatty acid concentrations and waist circumference

    Mocking, Roel J T; Lok, Anja; Assies, Johanna; Koeter, Maarten W J; Visser, Ieke; Ruhe, Eric; Bockting, Claudi L H; Schene, Aart H

    2013-01-01

    BACKGROUND: Fatty acid (FA)-alterations may mediate the mutual association between Major Depressive Disorder (MDD) and cardiovascular disease (CVD). However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-bindi

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

    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 transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  4. Novel radioiodinated {gamma}-hydroxybutyric acid analogues for radiolabeling and Photolinking of high-affinity {gamma}-hydroxybutyric acid binding sites

    Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola;

    2010-01-01

    ¿-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an endogenous substance that binds to low- and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analog and characterized its binding in rat brain...... homogenate and slices. Our data show that [(125)I]4-hydroxy-4-[4-(2-iodobenzyloxy)phenyl]butanoate ([(125)I]BnOPh-GHB) binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d), 7 nM; B(max), 61 pmol/mg protein). The binding is inhibited by GHB and selected analogs......, but not by ¿-aminobutyric acid. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether, the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites...

  5. Novel Radioiodinated γ-Hydroxybutyric Acid Analogues for Radiolabeling and Photolinking of High-Affinity γ-Hydroxybutyric Acid Binding Sites

    Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola;

    2010-01-01

    γ-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an endogenous substance that binds to low- and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a 125I-labeled GHB analog and characterized its binding in rat brain...... homogenate and slices. Our data show that [125I]4-hydroxy-4-[4-(2-iodobenzyloxy)phenyl]butanoate ([125I]BnOPh-GHB) binds to one site in rat brain cortical membranes with low nanomolar affinity (Kd, 7 nM; Bmax, 61 pmol/mg protein). The binding is inhibited by GHB and selected analogs, but not by γ......-aminobutyric acid. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether, the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [3H...

  6. Characterization of the differences in the cyclopiazonic acid binding mode to mammalian and P. Falciparum Ca2+ pumps: a computational study.

    Di Marino, Daniele

    2015-03-01

    Despite the investments in malaria research, an effective vaccine has not yet been developed and the causative parasites are becoming increasingly resistant to most of the available drugs. PfATP6, the sarco/endoplasmic reticulum Ca2+ pump (SERCA) of P. falciparum, has been recently genetically validated as a potential antimalarial target and cyclopiazonic acid (CPA) has been found to be a potent inhibitor of SERCAs in several organisms, including P. falciparum. In position 263, PfATP6 displays a leucine residue, whilst the corresponding position in the mammalian SERCA is occupied by a glutamic acid. The PfATP6 L263E mutation has been studied in relation to the artemisinin inhibitory effect on P. falciparum and recent studies have provided evidence that the parasite with this mutation is more susceptible to CPA. Here, we characterized, for the first time, the interaction of CPA with PfATP6 and its mammalian counterpart to understand similarities and differences in the mode of binding of the inhibitor to the two Ca2+ pumps. We found that, even though CPA does not directly interact with the residue in position 263, the presence of a hydrophobic residue in this position in PfATP6 rather than a negatively charged one, as in the mammalian SERCA, entails a conformational arrangement of the binding pocket which, in turn, determines a relaxation of CPA leading to a different binding mode of the compound. Our findings highlight differences between the plasmodial and human SERCA CPA-binding pockets that may be exploited to design CPA derivatives more selective toward PfATP6.

  7. Increase in Skin Autofluorescence and Release of Heart-Type Fatty Acid Binding Protein in Plasma Predicts Mortality of Hemodialysis Patients

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

    2013-01-01

    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 (DAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients.

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

    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.

  9. Expression, purification, crystallization and preliminary X-ray diffraction analysis of the VP8* sialic acid-binding domain of porcine rotavirus strain OSU

    Zhang, Yang-De, E-mail: zhangyd1960@yahoo.com.cn; Li, Hao [National Hepatobiliary and Enteric Surgery Research Center of The Ministry of Health, Xiangya Hospital, Central South University, Hunan Province (China); Liu, Hui; Pan, Yi-Feng [Biochemistry Laboratory, Institution of Biomedical Engineering, Central South University, Hunan Province (China); National Hepatobiliary and Enteric Surgery Research Center of The Ministry of Health, Xiangya Hospital, Central South University, Hunan Province (China)

    2007-02-01

    Porcine rotavirus strain OSU VP8* domain has been expressed, purified and crystallized. X-ray diffraction data from different crystal forms of the VP8* domain have been collected to 2.65 and 2.2 Å resolution, respectively. The rotavirus outer capsid spike protein VP4 is utilized in the process of rotavirus attachment to and membrane penetration of host cells. VP4 is cleaved by trypsin into two domains: VP8* and VP5*. The VP8* domain is implicated in initial interaction with sialic acid-containing cell-surface carbohydrates and triggers subsequent virus invasion. The VP8* domain from porcine OSU rotavirus was cloned and expressed in Escherichia coli. Different crystal forms (orthorhombic P2{sub 1}2{sub 1}2{sub 1} and tetragonal P4{sub 1}2{sub 1}2) were harvested from two distinct crystallization conditions. Diffraction data have been collected to 2.65 and 2.2 Å resolution and the VP8*{sub 65–224} structure was determined by molecular replacement.

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

    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.

  11. 心型脂肪酸结合蛋白与急性脑梗死%Heart Fatty Acid Binding Protein and Acute Cerebral Infarction

    邱晨红; 赵中; 董万利

    2007-01-01

    脂肪酸结合蛋白(FABP)是一种小分子胞内脂肪酸结合蛋白,与细胞生长、基因表达、离子通道的功能有关.细胞缺血损伤时,可发生胞内FABP渗漏.业已证实,脑梗死超早期可出现血清FABP水平增高.文章综述了FABP的生物学功能和在缺血性脑损伤中的表达机制.

  12. Tuning the Band Bending and Controlling the Surface Reactivity at Polar and Nonpolar Surfaces of ZnO through Phosphonic Acid Binding.

    McNeill, Alexandra R; Hyndman, Adam R; Reeves, Roger J; Downard, Alison J; Allen, Martin W

    2016-11-16

    ZnO is a prime candidate for future use in transparent electronics; however, development of practical materials requires attention to factors including control of its unusual surface band bending and surface reactivity. In this work, we have modified the O-polar (0001̅), Zn-polar (0001), and m-plane (101̅0) surfaces of ZnO with phosphonic acid (PA) derivatives and measured the effect on the surface band bending and surface sensitivity to atmospheric oxygen. Core level and valence band synchrotron X-ray photoemission spectroscopy was used to measure the surface band bending introduced by PA modifiers with substituents of opposite polarity dipole moment: octadecylphosphonic acid (ODPA) and 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctylphosphonic acid (F13OPA). Both PAs act as surface electron donors, increasing the downward band bending and the strength of the two-dimensional surface electron accumulation layer on all of the ZnO surfaces investigated. On the O-polar (0001̅) and m-plane (101̅0) surfaces, the ODPA modifier produced the largest increase in downward band bending relative to the hydroxyl-terminated unmodified surface of 0.55 and 0.35 eV, respectively. On the Zn-polar (0001) face, the F13OPA modifier gave the largest increase (by 0.50 eV) producing a total downward band bending of 1.00 eV, representing ∼30% of the ZnO band gap. Ultraviolet (UV) photoinduced surface wettability and photoconductivity measurements demonstrated that the PA modifiers are effective at decreasing the sensitivity of the surface toward atmospheric oxygen. Modification with PA derivatives produced a large increase in the persistence of UV-induced photoconductivity and a large reduction in UV-induced changes in surface wettability.

  13. Characterization of the N-Acetyl-5-neuraminic Acid-binding Site of the Extracytoplasmic Solute Receptor (SiaP) of Nontypeable Haemophilus influenzae Strain 2019

    Johnston, Jason W.; Coussens, Nathan P.; Allen, Simon; Houtman, Jon C.D.; Turner, Keith H.; Zaleski, Anthony; Ramaswamy, S.; Gibson, Bradford W.; Apicella, Michael A. (Iowa); (Buck Inst.)

    2012-11-14

    Nontypeable Haemophilus influenzae is an opportunistic human pathogen causing otitis media in children and chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The outer membrane of nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many of which incorporate sialic acid as a terminal nonreducing sugar. Sialic acid has been demonstrated to be an important factor in the survival of the bacteria within the host environment. H. influenzae is incapable of synthesizing sialic acid and is dependent on scavenging free sialic acid from the host environment. To achieve this, H. influenzae utilizes a tripartite ATP-independent periplasmic transporter. In this study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4 {angstrom} resolution. Thermodynamic characterization of Neu5Ac binding shows this interaction is enthalpically driven with a substantial unfavorable contribution from entropy. This is expected because the binding of SiaP to Neu5Ac is mediated by numerous hydrogen bonds and has several buried water molecules. Point mutations targeting specific amino acids were introduced in the putative binding site. Complementation with the mutated siaP constructs resulted either in full, partial, or no complementation, depending on the role of specific residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K point mutation confirmed the observation of reduced incorporation of Neu5Ac into the LOS. The decreased ability of H. influenzae to import sialic acid had negative effects on resistance to complement-mediated killing and viability of biofilms in vitro, confirming the importance of sialic acid transport to the bacterium.

  14. Synthesis, CMC Determination, Antimicrobial Activity and Nucleic Acid Binding of A Surfactant Copper(II) Complex Containing Phenanthroline and Alanine Schiff-Base.

    Nagaraj, Karuppiah; Sakthinathan, Subramanian; Arunachalam, Sankaralingam

    2014-03-01

    A new water-soluble surfactant copper(II) complex [Cu(sal-ala)(phen)(DA)] (sal-ala = salicylalanine, phen = 1,10-phenanthroline, DA = dodecylamine), has been synthesized and characterized by physico-chemical and spectroscopic methods. The critical micelle concentration (CMC) values of this surfactant-copper(II) complex in aqueous solution were obtained from conductance measurements. Specific conductivity data (at 303, 308, 313. 318 and 323 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (ΔG(0)m, ΔH(0)m and ΔS(0)m). The interaction of this complex with nucleic acids (DNA and RNA) has been explored by using electronic absorption spectral titration, competitive binding experiment, cyclic voltammetry, circular dichroism (CD) spectra, and viscosity measurements. Electronic absorption studies have revealed that the complex can bind to nucleic acids by the intercalative binding mode which has been verified by viscosity measurements. The DNA binding constants have also been calculated (Kb = 1.2 × 10(5) M(-1) for DNA and Kb = 1.6 × 10(5) M(-1) for RNA). Competitive binding study with ethidium bromide (EB) showed that the complex exhibits the ability to displace the DNA-bound-EB indicating that the complex binds to DNA in strong competition with EB for the intercalative binding site. The presence of hydrophobic ligands, alanine Schiff-base, phenanthroline and long aliphatic chain amine in the complex were responsible for this strong intercalative binding. The surfactant-copper (II) complex was screened for its antibacterial and antifungal activities against various microorganisms. The results were compared with the standard drugs, amikacin(antibacterial) and ketokonazole(antifungal).

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

    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.

  16. Structure of a fatty acid-binding protein from Bacillus subtilis determined by sulfur-SAD phasing using in-house chromium radiation

    Nan, Jie; Zhou, Yanfeng; Yang, Cheng;

    2009-01-01

    electron-density map was obtained after density modification. The model of BsDegV was built automatically and a palmitate was found tightly bound in the active site. Sequence alignment and comparisons with other known DegV structures provided further insight into the specificity of fatty-acid selection...

  17. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: Identification of an RGFRRR motif governing fungal cell entry

    Sagaram, Uma S.; El-Mounadi, Kaoutar; Buchko, Garry W.; Berg, Howard R.; Kaur, Jagdeep; Pandurangi, Raghoottama; Smith, Thomas J.; Shah, Dilip

    2013-12-04

    A highly conserved plant defensin MtDef4 potently inhibits the growth of a filamentous fungus Fusarium graminearum. MtDef4 is internalized by cells of F. graminearum. To determine its mechanism of fungal cell entry and antifungal action, NMR solution structure of MtDef4 has been determined. The analysis of its structure has revealed a positively charged patch on the surface of the protein consisting of arginine residues in its γ-core signature, a major determinant of the antifungal activity of MtDef4. Here, we report functional analysis of the RGFRRR motif of the γ-core signature of MtDef4. The replacement of RGFRRR to AAAARR or to RGFRAA not only abolishes fungal cell entry but also results in loss of the antifungal activity of MtDef4. MtDef4 binds strongly to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Mutations of RGFRRR which abolish fungal cell entry of MtDef4 also impair its binding to PA. Our results suggest that RGFRRR motif is a translocation signal for entry of MtDef4 into fungal cells and that this positively charged motif likely mediates interaction of this defensin with PA as part of its antifungal action.

  18. Liver-type fatty acid-binding protein and lipid transport%肝型脂肪酸结合蛋白与脂类转运

    张虎; 朱金玲; 张玉萍; 罗佳滨

    2008-01-01

    肝型脂肪酸结合蛋白(L-FABP)是脂肪酸结合蛋白(FABPs)家族成员之一,与其他成员结构和功能方面有相同之处又有区别.L-FABP主要表达于肝脏组织和小肠,介导脂肪酸及多种疏水基团转运,涉及多种疾病的发病机制.多年来其转运机制备受关注,研究方法从体外到体内,从细胞分子水平到基因沉默动物水平.虽然L-FABP的转运机制研究越来越深入,但是仍需要进一步加强基础研究,揭示其调控脂类转运的机制.本文主要对L-FABP的特性、结构及体内研究现状作一综述.

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

    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.

  20. Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019.

    Johnston, Jason W; Coussens, Nathan P; Allen, Simon; Houtman, Jon C D; Turner, Keith H; Zaleski, Anthony; Ramaswamy, S; Gibson, Bradford W; Apicella, Michael A

    2008-01-11

    Nontypeable Haemophilus influenzae is an opportunistic human pathogen causing otitis media in children and chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The outer membrane of nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many of which incorporate sialic acid as a terminal nonreducing sugar. Sialic acid has been demonstrated to be an important factor in the survival of the bacteria within the host environment. H. influenzae is incapable of synthesizing sialic acid and is dependent on scavenging free sialic acid from the host environment. To achieve this, H. influenzae utilizes a tripartite ATP-independent periplasmic transporter. In this study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4A resolution. Thermodynamic characterization of Neu5Ac binding shows this interaction is enthalpically driven with a substantial unfavorable contribution from entropy. This is expected because the binding of SiaP to Neu5Ac is mediated by numerous hydrogen bonds and has several buried water molecules. Point mutations targeting specific amino acids were introduced in the putative binding site. Complementation with the mutated siaP constructs resulted either in full, partial, or no complementation, depending on the role of specific residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K point mutation confirmed the observation of reduced incorporation of Neu5Ac into the LOS. The decreased ability of H. influenzae to import sialic acid had negative effects on resistance to complement-mediated killing and viability of biofilms in vitro, confirming the importance of sialic acid transport to the bacterium.

  1. Dimerization and thiol sensitivity of the salicylic acid binding thimet oligopeptidases TOP1 and TOP2 define their functions in redox-sensitive cellular pathways

    Timothy James Westlake

    2015-05-01

    Full Text Available A long-term goal in plant research is to understand how plants integrate signals from multiple environmental stressors. The importance of salicylic acid (SA in plant response to biotic and abiotic stress is known, yet the molecular details of the SA-mediated pathways are insufficiently understood. Our recent work identified the peptidases TOP1 and TOP2 as critical components in plant response to pathogens and programmed cell death. In this study, we investigated the characteristics of TOPs related to the regulation of their enzymatic activity and function in oxidative stress response. We determined that TOP1 and TOP2 interact with themselves and each other and their ability to associate in dimers is influenced by SA. Biochemical characterization of the organellar TOP1 indicated sensitivity to redox changes and robust activity under a range of pH values. Treatments of top mutants with Methyl Viologen (MV revealed TOP1 and TOP2 as a modulators of the plant tolerance to MV, and that exogenous SA alleviates the toxicity of MV in top background. Finally, we generated a TOP-centered computational model of a plant cell whose simulation outputs replicate experimental findings and predict novel functions of TOP1 and TOP2. Altogether, our work indicates that TOP1 and TOP2 mediate plant responses to oxidative stress through spatially separated pathways and positions proteolysis in a network for plant response to diverse stressors.

  2. The increase of fatty acid-binding protein aP2 in overweight and obese children: interactions with dietary fat and impact on measures of subclinical inflammation

    Aeberli, I.; Beljean, N.; Lehmann, R.; I'Allemand, D.; Spinas, G.A.; Zimmermann, M.B.

    2008-01-01

    In adults, circulating aP2 may link obesity, inflammation and the metabolic syndrome, but there are few data in children. Experimental models support that dietary factors, particularly dietary fat, may be major determinants of phenotype. OBJECTIVE: The aim of this study was to investigate, in normal

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

    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.

  4. Radiosynthesis and Evaluation of [(11)C]3-Hydroxycyclopent-1-enecarboxylic Acid as Potential PET Ligand for the High-Affinity γ-Hydroxybutyric Acid Binding Sites

    Jensen, Claus H; Hansen, Hanne D; Bay, Tina

    2017-01-01

    the (11)C-labeling and subsequent evaluation of [(11)C]HOCPCA in a domestic pig, as a PET-radioligand for visualization of the high-affinity GHB binding sites in the live pig brain. To investigate the regional binding of HOCPCA in pig brain prior to in vivo PET studies, in vitro quantitative......γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete...... understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report...

  5. Radiosynthesis and Evaluation of [(11)C]3-Hydroxycyclopent-1-enecarboxylic Acid as Potential PET Ligand for the High-Affinity γ-Hydroxybutyric Acid Binding Sites.

    Jensen, Claus H; Hansen, Hanne D; Bay, Tina; Vogensen, Stine B; Lehel, Szabolcs; Thiesen, Louise; Bundgaard, Christoffer; Clausen, Rasmus P; Knudsen, Gitte M; Herth, Matthias M; Wellendorph, Petrine; Frølund, Bente

    2017-01-18

    γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report the (11)C-labeling and subsequent evaluation of [(11)C]HOCPCA in a domestic pig, as a PET-radioligand for visualization of the high-affinity GHB binding sites in the live pig brain. To investigate the regional binding of HOCPCA in pig brain prior to in vivo PET studies, in vitro quantitative autoradiography on sections of pig brain was performed using [(3)H]HOCPCA. In vivo evaluation of [(11)C]HOCPCA showed no brain uptake, possibly due to a limited uptake of HOCPCA by the MCT1 transporter at tracer doses of [(11)C]HOCPCA.

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

    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.

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

    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.

  8. Optimisation of production of a domoic acid-binding scFv antibody fragment in Escherichia coli using molecular chaperones and functional immobilisation on a mesoporous silicate support.

    Hu, Xuejun; O'Hara, Liam; White, Simon; Magner, Edmond; Kane, Marian; Wall, J Gerard

    2007-03-01

    Domoic acid is a potent neurotoxin that can lead to amnesic shellfish poisoning in humans through ingestion of contaminated shellfish. We have produced and purified an anti-domoic acid single-chain Fragment variable (scFv) antibody fragment from the Escherichia coli periplasm. Yields of functional protein were increased by up to 100-fold upon co-production of E. coli DnaKJE molecular chaperones but co-overproduction of GroESL led to a reduction in solubility of the scFv. Co-production of the peptidyl-prolyl isomerase trigger factor resulted in accumulation of unprocessed scFv in the E. coli cytoplasm. This was due to an apparent bottleneck in translocation of the cytoplasmic membrane by the recombinant polypeptide. Co-expression of the E. coli disulfide bond isomerase dsbC increased scFv yields by delaying lysis of the host bacterial cells though this effect was not synergistic with molecular chaperone co-production. Meanwhile, use of a cold-shock promoter for protein production led to accumulation of greater amounts of scFv polypeptide which was predominantly in insoluble form and could not be rescued by chaperones. Purification of the scFv was achieved using an optimised metal affinity chromatography procedure and the purified protein bound domoic acid when immobilised on a mesoporous silicate support. The work outlines the potential benefit of applying a molecular chaperone/folding catalyst screening approach to improve antibody fragment production for applications such as sensor development.

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

    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.

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

    2015-01-01

    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 DH...

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

    2015-01-01

    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 lact...

  12. NCBI nr-aa BLAST: CBRC-CFAM-01-0026 [SEVENS

    Full Text Available CBRC-CFAM-01-0026 ref|NP_001077062.1| immunoglobulin-like transcript 11 A [Equus ca...ballus] dbj|BAD12826.1| immunoglobulin-like transcript 11 protein [Equus caballus] dbj|BAD12827.1| immunoglobulin-like transcript 11 protein [Equus caballus] NP_001077062.1 1e-29 59% ...

  13. Analysis of Ligand Binding Specificity of Chicken Liver Basic Fatty Acid Binding Protein (Lb-FABP)and Liver Fatty Acid Binding Protein (L-FABP)%鸡肝脏基础型脂肪酸结合蛋白和肝脏脂肪酸结合蛋白配基结合特性分析

    赵玉芳; 冷丽; 王守志; 张慧; 王宇祥; 王启贵; 李辉

    2013-01-01

    为探讨鸡肝脏基础型脂肪酸结合蛋白(Lb-FABP)和肝脏脂肪酸结合蛋白(L-FABP)蛋白的配基结合属性,诱导表达并利用Glutathione Sepharose 4B亲和层析纯化了鸡的GST/Lb-FABP和GST/L-FABP融合蛋白,得到的GST/Lb-FABP和GST/L-FABP融合蛋白大小分别为38 ku和40 ku.将鸡的Lb-FABP和L-FABP分别与1,8-ANS探针结合,结果显示Lb-FABP和L-FABP均表现出对荧光探针的较强结合能力;为进一步测定棕榈酸、花生四烯酸、油酸、胆汁酸和维甲酸这5种配体与Lb-FABP和L-FABP结合的特异性和亲合力,使用这些脂质分子与1,8-ANS探针进行置换分析,结果表明鸡Lb-FABP与维甲酸结合能力最强,而L-FABP与油酸的结合能力最强.本研究结果为深入探究Lb-FABP和L-FABP的生物学功能提供了良好的基础.

  14. Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes

    Dharmadhikari, Gitanjali; Stolz, Katharina; Hauke, Michael; Morgan, Noel G.; Varki, Ajit; de Koning, Eelco; Kelm, Sørge; Maedler, Kathrin

    2017-01-01

    Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore β-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented β-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of β-cell function and survival. PMID:28378743

  15. Design, Synthesis, and in Vitro Pharmacology of New Radiolabeled γ-Hydroxybutyric Acid Analogues Including Photolabile Analogues with Irreversible Binding to the High-Affinity γ-Hydroxybutyric Acid Binding Sites

    Sabbatini, Paola; Wellendorph, Petrine; Høg, Signe;

    2010-01-01

    γ-Hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report...... the design and synthesis of the first 125I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites....

  16. A new point mutation in the deoxyribonuclic acid-binding domain of the vitamine D receptor in a kindred with hereditary 1,25-dihydroxyvitamin d-resistant rickets

    Yagi, Hideki; Miyake, Hiroshi; Nagashima, Kanji; Kuroume, Takayoshi (Gunma Univ. School of Medicine (Japan)); Ozone, K.; Pike, J.W. (Baylor College of Medicine, Houston, TX (United States))

    1993-02-01

    Hereditary 1,25-dihydroxyvitamin D [1,25-(OH)[sub 2]D]-resistant rickets (HVDRR) is a rare disorder characterized by rickets, alopecia, hypocalcemia, secondary hyperparathyroidism, and normal or elevated serum 1,25-dihydroxyvitamin D levels. The authors describe a patient with typical clinical characteristics of HVDRR, except that elevated levels of serum phosphorus were present coincident with increased levels of serum intact PTH. The patient was treated with high dose calcium infusion after an ineffective treatment with 1[alpha]-hydroxyvitamin D[sub 3]; serum calcium and phosphorus as well as intact PTH and alkaline phosphatase levels were normalized. Evaluation of phytohemagglutinin-activated lymphocytes derived from this patient revealed that 1,25-(OH)[sub 2]D[sub 3] was unable to inhibit thymidine incooperation, a result that contrast with the capacity of 1,25-(OH)[sub 2]D[sub 3] to inhibit uptake into normal activated lymphocytes. 1,25-(OH)[sub 2]D[sub 3] did not induce human osteocalcin promoter activity after transfection of this DNA linked to a reporter gene into patient cells. Cointroduction of a human vitamin D receptor (VDR) cDNA expression vector with the reporter plasmid, however, restored the hormone response. Evaluation of extracts from the patient cells for VDR DNA binding revealed a defect in DNA binding. Analysis of genomic DNA from the patient's cells by PCR confirmed the presence of a point mutation in exon 2 of the VDR. This exon directs synthesis of a portion of the DNA-binding domain of the receptor. We conclude that the genetic basis for 1,25-(OH)[sub 2]D[sub 3] resistance in this kindred with VDR-positive HVDRR is due to a single base mutation in the VDR that leads to production of a receptor unable to interact appropriately with DNA. 20 refs., 3 figs., 1 tab.

  17. 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.

    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.

  18. 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

    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.

  19. 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

    Pedersen, Lotte Bang; Birkelund, S; 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...

  20. Elucidating the domain architecture and functions of non-core RAG1: The capacity of a non-core zinc-binding domain to function in nuclear import and nucleic acid binding

    Zhao Shuying

    2011-05-01

    Full Text Available Abstract Background The repertoire of the antigen-binding receptors originates from the rearrangement of immunoglobulin and T-cell receptor genetic loci in a process known as V(DJ recombination. The initial site-specific DNA cleavage steps of this process are catalyzed by the lymphoid specific proteins RAG1 and RAG2. The majority of studies on RAG1 and RAG2 have focused on the minimal, core regions required for catalytic activity. Though not absolutely required, non-core regions of RAG1 and RAG2 have been shown to influence the efficiency and fidelity of the recombination reaction. Results Using a partial proteolysis approach in combination with bioinformatics analyses, we identified the domain boundaries of a structural domain that is present in the 380-residue N-terminal non-core region of RAG1. We term this domain the Central Non-core Domain (CND; residues 87-217. Conclusions We show how the CND alone, and in combination with other regions of non-core RAG1, functions in nuclear localization, zinc coordination, and interactions with nucleic acid. Together, these results demonstrate the multiple roles that the non-core region can play in the function of the full length protein.

  1. Clinical Value of Heart-Type Fatty Acid-Binding Protein in Pulmonary Heart Disease%心型脂肪酸结合蛋白在心肺疾病中的研究进展

    王勇

    2010-01-01

    脂肪酸结合蛋白是一种更为敏感的反应组织损伤的新型生物标记物.尤其是心型脂肪酸结合蛋白,它是一种在心肌细胞质中含量丰富的小分子蛋白,在心肺疾病的早期诊断、危险分层、预后评价中具有广泛的临床价值.

  2. Hereditary folate malabsorption: A positively charged amino acid at position 113 of the proton-coupled folate transporter (PCFT/SLC46A1) is required for folic acid binding

    Lasry, Inbal; Berman, Bluma [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Glaser, Fabian [Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion, Haifa 32000 (Israel); Jansen, Gerrit [Department of Rheumatology, VU University Medical Center, Amsterdam (Netherlands); Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il [The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)

    2009-08-28

    The proton-coupled folate transporter (PCFT/SLC46A1) mediates intestinal folate uptake at acidic pH. Some loss of folic acid (FA) transport mutations in PCFT from hereditary folate malabsorption (HFM) patients cluster in R113, thereby suggesting a functional role for this residue. Herein, unlike non-conservative substitutions, an R113H mutant displayed 80-fold increase in the FA transport Km while retaining parental Vmax, hence indicating a major fall in folate substrate affinity. Furthermore, consistent with the preservation of 9% of parental transport activity, R113H transfectants displayed a substantial decrease in the FA growth requirement relative to mock transfectants. Homology modeling based on the crystal structures of the Escherichia coli transporter homologues EmrD and glycerol-3-phosphate transporter revealed that the R113H rotamer properly protrudes into the cytoplasmic face of the minor cleft normally occupied by R113. These findings constitute the first demonstration that a basic amino acid at position 113 is required for folate substrate binding.

  3. The correlation study of liver type fatty acid-binding protein and chronic kidney disease%肝脏型脂肪酸结合蛋白与慢性肾脏病的相关性研究

    郑伟; 那宇; 袁洪萍

    2011-01-01

    Objective To investigate the relationship between L-FABP and CKD ,Weassessed the clinical parameters of urinary L-FABP ,serum Scratinine and glom erular filtration rate.Methods Five groups were involved in this experiment:without liver injury CKD group (n = 60) and healthy group (n =20),CKD1-2 stage group(n =20),CKD3-4 stage group(n =20),CKD5 stage group(n = 20 ).To obtain serum and urinary sam ples of studied objects ,the level of urinary L-FABP ,serum Scratinine and glom erular filtration rate were m easured by EL ISA and biochel icalm ethods respectively.Results R ank and inspection show sCKD W ilconxon com parison of the urinary L-FABP levels during statistically significant differences (H = 69.05,P<0.001),subgroup analysis showed CKD 1-2 stage urinary L-FABP levels higher than health group ,CKD 3-4 stage urinary L-FABP levels higher than the CKD 1-2 stage ,CKD 5 stage urinary L-FABP level higher than the CKD 3-4 stage.Pearson correlation analysis show s urinary L-FABP levels and GFR is a significant negative correlation (rs= 0.942,P<0.001),and Scr are markedly positive (rs=0.948,P<0.001).Conclusion Urinary L-FABP levels increased significantly when chronic kidney disease ,with CKD stage of development,urinary L-FABP levels gradually rise.ueinary L-FABP levels and GFR is a significant negative correlation ,associated with Scr is significantly positive.As a clinical biom arker,urinary L-FABP can help to diagnose chronic kidney disease.%目的 通过对尿L-FABP、血肌酐(Scr)、肾小球滤过率(GFR)等临床参数的测定和评价,探索尿L-FABP与慢性肾脏病的相关性.方法 实验选取无肝脏损害慢性肾脏病组(CKD组)60例,CKD1-2期20例、CKD3-4期20例、CKD5期20例,健康组20例.留取研究对象的血液及尿液标本,检测血肌酐(Scr)、肾小球滤过率(GFR)及尿L-FABP水平.结果 Wilconxon秩和检验显示CKD各分期间尿L-FABP水平比较差异有统计学意义(H=69.05,P<0.001),亚组分析显示CKD1-2期尿L-FABP水平高于健康组,CKD3-4期尿L-FABP水平高于CKD1-2期,CKD5期尿L-FABP水平高于CKD3-4期.Pearson相关性分析显示尿L-FABP水平与GFR 呈显著负相关(rs=-0.942,P<0.001),与Scr 呈显著正相关(rs=0.948,P<0.001).结论 慢性肾脏病时尿L-FABP水平显著升高,随着CKD分期的进展,尿L-FABP水平逐渐上升.尿L-FABP与GFR 呈显著负相关,与Scr 呈显著正相关.尿L-FABP可以作为协助诊断慢性肾脏病的临床生化指标.

  4. Urinary liver-type fatty acid-binding protein as a prognostic biomarker in patients with acute kidney injury%尿L-FABP在预测急性肾损伤预后中的意义

    薛婧; 陈彩妹; 王凉; 孙铸兴

    2014-01-01

    目的 观察住院急性肾损伤(AKI)患者尿肝脏型脂肪酸结合蛋白(L-FABP)的水平,分析其对肾脏替代治疗(RRT)及住院死亡的预测能力.方法 前瞻性收集经肾内科医师会诊确诊AKI患者103例,留取会诊时患者的血尿标本,检测其血尿肌酐及尿L-FABP水平.运用ROC曲线评估尿L-FABP预测AKI患者预后的准确性.结果 ①103例患者中,50例接受了RRT(48.5%),45例住院期间死亡(42.7%);②尿L-FABP可以预测行机械通气及合并脓毒症AKI患者是否需要进行RRT,AUC分别为0.822和0.743(P <0.001);③尿L-FABP可以预测AKI患者住院病死率,当截断值为124.95 ng/mg·Cr,敏感性和特异性均较高.对未发生心衰、行机械通气、AKIN-2和3期的AKI患者,尿L-FABP预测其住院期间死亡准确性好,AUC分别为0.844、0.832、0.912和0.900(P <0.05).校正了年龄、性别、急性肾衰预后评分(ATN-ISS)后,尿L-FABP高于均值组的患者发生住院期间死亡的风险比低于均值组高1.24倍(HR 2.24,95%CI 1.50~3.09,P=0.02).结论 住院患者中AKI的发生率及死亡率高.尿L-FABP可以预测行机械通气、合并脓毒症的AKI患者是否需要RRT,以及AKI患者住院期间死亡率.

  5. 大鼠尿肝脏型脂肪酸结合蛋白与急性肾损伤%URINARY LIVER-TYPE FATTY ACID-BINDING PROTEIN AND ACUTE KIDNEY INJURY IN RATS

    巴应贵

    2014-01-01

    目的 观察、了解低渗造影剂碘比乐诱导的造影剂急性肾损伤(AKI)不同时间段大鼠血半胱氨酸蛋白酶抑制蛋白C(CysC)、尿肝脏型脂肪酸结合蛋白(L-FABP)表达变化及其意义.方法 将60只SD大鼠,随机分为造影剂急性肾损伤(AKI)组(AKI组,n=30)和非AKI(非AKI组,n=30),每组分为6个亚组,包括2、4、6、12、24、48 h组,观察各亚组血CysC、尿L-FABP不同时间段的表达变化.结果 与非AKI组相比较,AKI组血CysC的表达:变化造模后12、24、48 h大鼠CysC水平均显著升高,且两两比较差别有统计学意义(P均<0.05).尿L-FABP水平在第8、12、24、48 h非AKI与AKI组相比较差别有统计学意义(P<0.05).Scr的相关性分析显示,不同AKI组尿L-FABP、CysC呈正相关(r分别为0.900、0.954,P<0.05);CysC的相关性分析显示,不同AKI组尿L-FABP、Scr呈正相关(r分别为0.937、0.953,P<0.05);AKI组尿L-FABP的相关性分析显示,不同AKI组尿L-FABP、Scr呈正相关(r分别为0.937、0.953,P<0.05).结论 尿L-FABP为急性肾损伤早期敏感的生物标记物.

  6. 鸡L-FABP抗血清制备及组织表达特性分析%Preparation of Antiserums against Chicken Liver-type Fatty Acid Binding Protein (L-FABP) and Tissue Expression Analyses of L-FABP

    石慧; 王启贵; 王宇祥; 王宁; 李辉

    2008-01-01

    为制备鸡肝脏型脂肪酸结合蛋白(L-FABP)的多克隆抗血清,并分析L-FABP的组织表达特性,利用RT-PCR扩增L-FABP基因,构建鸡L-FABP基因的GST融合蛋白表达质粒pGEX-4T/L-FABP.将重组表达质粒转化大肠杆菌BL21,IPTG诱导产生GST/L-FABP融合蛋白,用亲和层析纯化目的蛋白,将纯化的GST/L-FABP融合蛋白免疫家兔制备抗血清,并利用此抗血清分析鸡L-FABP基因的组织表达特性.诱导得到了1个40 ku(14 ku L-FABP+ 26 ku GST)的融合蛋白,获得效价较高、特异性强的鸡L-FABP的抗血清.鸡L-FABP的组织表达特性研究结果表明,该基因在肝脏和小肠组织中有较高表达,但在心脏、脂肪、肌肉、肌胃、脾、肺和肾中没有检测到表达信号.

  7. 脂肪酸结合蛋白在人乳腺癌组织的表达及意义%Expression of fatty acid binding protein in human breast cancer tissues

    李华; 吕青; 董立华; 薛晖; 周鸿鹰; 羊惠君

    2007-01-01

    目的:研究脂肪酸结合蛋白(FABP)mRNA及蛋白质在浸润性乳腺导管癌和乳腺纤维腺瘤的表达及分布, 探寻人浸润性乳腺导管癌新的分子标志, 为乳腺癌的靶向治疗提供理论依据.方法:用半定量逆转录聚合酶链反应、免疫组织化学染色和Western blot等方法检测脂肪细胞型FABP、心型或骨骼肌型FABP、脑型FABP、表皮或牛皮癣型FABP、肝型FABP、小肠型FABP和胃型FABP mRNA及蛋白质在35例浸润性乳腺导管癌, 16例乳腺纤维腺瘤组织中的表达变化.结果:RT-PCR 结果显示A-、 B-、 I-和G-FABPs mRNA在两种组织的表达差异无统计学意义(P>0.05);但E-、 H-和L-FABP mRNA在浸润性导管癌的表达较纤维腺瘤显著升高(P<0.05).免疫组织化学染色显示, E-、 L-和H-FABP在浸润性导管癌的阳性细胞百分数较纤维腺瘤明显上调(P<0.05), 分布范围更广.Western blot分析结果进一步证实, E-、 L-和H-FABP蛋白质在浸润性导管癌表达明显上调(P<0.05).结论:E-、 L-和H-FABP与浸润性乳腺导管癌的发生发展有关, 对进一步探寻浸润性乳腺导管癌的分子标志及治疗途径具有理论意义.

  8. 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

    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

  9. High-throughput and sensitive screening of compounds with deoxyribonucleic acid-binding activity by a high-performance liquid chromatography-tandem mass spectrometry-fluorescence detection technique using palmatine as a fluorescence probe.

    Fu, Qingrong; Wang, Hong; Lan, Yuexiang; Li, Sen; Hashi, Yuki; Chen, Shizhong

    2014-01-03

    A high-throughput biochemical detection method based on the combination of high-performance liquid chromatography (HPLC), multiple-stage mass spectrometry (MS(n)) and DNA-binding activity assay was developed and validated for the simultaneous screening and identification of DNA-binding compounds in complex samples. Palmatine was used as a sensitive, nontoxic and environmentally friendly DNA fluorescence probe. HPLC fingerprints, ultraviolet absorption spectra, MS(n) fragments of components, and DNA-binding activity profiles could be simultaneously recorded during real-time analysis. Using the proposed method, 25 compounds were identified from Lophatherum gracile Brongn extracts, of which 18 were novel compounds first identified in these extracts. Nineteen compounds showed DNA-binding activity, most of which were flavone glycosides, with distinct dose-effect and structure-activity relationships. The method was validated and was proven to have a good linearity in the range of concentrations used in the study. The limit of detection was 0.2020nmol. Our study indicated that the proposed method was sensitive, accurate, precise and reliable to be used for simultaneous screening and identification of DNA-binding compounds in complex samples.

  10. Salicylic acid binding of mitochondrial alpha-ketoglutarate dehydrogenase E2 affects mitochondrial oxidative phosphorylation and electron transport chain components and plays a role in basal defense against tobacco mosaic virus in tomato.

    Liao, Yangwenke; Tian, Miaoying; Zhang, Huan; Li, Xin; Wang, Yu; Xia, Xiaojian; Zhou, Jie; Zhou, Yanhong; Yu, Jingquan; Shi, Kai; Klessig, Daniel F

    2015-02-01

    Salicylic acid (SA) plays a critical role in plant defense against pathogen invasion. SA-induced viral defense in plants is distinct from the pathways mediating bacterial and fungal defense and involves a specific pathway mediated by mitochondria; however, the underlying mechanisms remain largely unknown. The SA-binding activity of the recombinant tomato (Solanum lycopersicum) alpha-ketoglutarate dehydrogenase (Slα-kGDH) E2 subunit of the tricarboxylic acid (TCA) cycle was characterized. The biological role of this binding in plant defenses against tobacco mosaic virus (TMV) was further investigated via Slα-kGDH E2 silencing and transient overexpression in plants. Slα-kGDH E2 was found to bind SA in two independent assays. SA treatment, as well as Slα-kGDH E2 silencing, increased resistance to TMV. SA did not further enhance TMV defense in Slα-kGDH E2-silenced tomato plants but did reduce TMV susceptibility in Nicotiana benthamiana plants transiently overexpressing Slα-kGDH E2. Furthermore, Slα-kGDH E2-silencing-induced TMV resistance was fully blocked by bongkrekic acid application and alternative oxidase 1a silencing. These results indicated that binding by Slα-kGDH E2 of SA acts upstream of and affects the mitochondrial electron transport chain, which plays an important role in basal defense against TMV. The findings of this study help to elucidate the mechanisms of SA-induced viral defense.

  11. 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

    贾亚军; 王晓婷; 许娜; 郭娜; 邢邯

    2015-01-01

    [目的]对大豆(Glycine max)水杨酸结合蛋白基因GmSABP2进行克隆与表达分析,并转化拟南芥进行耐盐、耐干旱分析,进一步了解该基因耐盐、耐干旱的分子机制.[方法]以拟南芥SABP2为探针,搜索大豆基因组数据库,从中挑选出同源性最高的序列,将其命名为 GmSABP2.利用电子克隆技术,从大豆叶子中克隆得到大豆水杨酸结合蛋白基因GmSABP2.通过DNAMAN程序进行氨基酸的多序列比对,利用NCBI的CD-search进行氨基酸的保守结构域分析,应用MEGA程序进行系统进化树分析.对大豆幼苗进行盐和干旱胁迫处理来分析其在胁迫下的表型变化.通过Real time-PCR分析大豆幼苗在盐和干旱处理条件下GmSABP2的表达特性.利用Gateway技术构建植物表达载体pEarleyGate103-GmSABP2,转入根癌农杆菌EHA105,利用蘸花法侵染拟南芥,经抗性筛选得到转基因株系.对野生型植株和转基因植株进行盐和干旱胁迫处理,并统计在胁迫条件下两者的种子萌发率、主根长和成熟植株的存活率.[结果]克隆得到GmSABP2的cDNA序列,序列全长1 235 bp,其开放阅读框为786 bp,编码261个氨基酸,分子量为29.15 kD,等电点为5.58.氨基酸序列比对发现大豆和毛白杨、可可以及烟草相似度较高.利用NCBI的CD-search发现大豆SABP2序列中存在一个Abhydrolase_6(pfam:12697)水解酶保守结构域.大豆SABP2蛋白属于α/β水解酶超家族.应用MEGA程序构建多物种的系统发生树,发现大豆和毛白杨及可可亲缘关系较近,而与拟南芥亲缘关系较远.对大豆幼苗胁迫后的表型分析发现,在盐和干旱条件下大豆幼苗均受到明显的胁迫效应.Real time-PCR分析表明大豆幼苗叶子中的GmSABP2在盐和干旱处理条件下均上调表达.拟南芥耐逆性分析发现,在正常培养条件下,野生型植株和转基因株系均能正常萌发、生长.在高盐(150 mmol·L-1 NaCl)处理条件下,野生型植株的种子萌发率为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 cDNA sequence of GmSABP2 was obtained and the open reading frame is 786 bp and total length of the sequence is 1 235 bp, encoding 261 amino acids. And molecular weight is 29.15 kD, an isoelectric point is 5.58. The amino acid sequence alignment and phylogenetic analysis showed that GmSABP2 and tobacco SABP2,Rauvolfia serpentina PNAE had the highest similarity. Using the CD-search of NCBI, it was found that the Abhydrolase_6 (pfam: 12697) as conserved domain hydrolases. Soybean SABP2 protein belongs to SABP2α/β hydrolase superfamily. Using MEGA program to build a system of species multiple phylogenetic tree, it was found that SABP2 of soybeans,Theobroma cacao SABP2 and Solanum lycopersicum SABP2 have a close genetic relationship, but has a distant genetic relationship with Arabidopsis SABP2. The phenotype of soybean seedlings under salt and drought conditions was analyzed and it was found that there were significant stress effects. Real time-PCR analysis showed that GmSABP2 under salt and drought conditions were upregulated expression.Arabidopsis thaliana resistance analysis showed that under normal culture conditions, the wild-type plants and transgenic plants could germinate and grow. Under 150 mmol·L-1 NaCl treatment conditions, seed germination rate of wild-type plants was 38%, seedling root length after 12 days was 0.4 cm and the survival rate of mature plants was 49%; The seed germination rate of transgenic lines was 67%, seedling root length after 12 days was 1.1 cm and mature plants survival was 78%. Under 20% PEG6000 treatment conditions, the seed germination rate of wild-type plants was 31%, seedling root length after 12 days was 0.5 cm and mature plants survival rate was 36%; The seed germination rate of transgenic lines was 57%, seedling root length after 12 days was 1.0 cm and mature plants survival rate was 66%.[Conclusion] The GmSABP2 gene increases the resistance of Arabidopsis plants under salt and drought conditions.

  12. Seq2Logo: a method for construction and visualization of amino acid binding motifs and sequence profiles including sequence weighting, pseudo counts and two-sided representation of amino acid enrichment and depletion

    Thomsen, Martin Christen Frølund; Nielsen, Morten

    2012-01-01

    Seq2Logo is a web-based sequence logo generator. Sequence logos are a graphical representation of the information content stored in a multiple sequence alignment (MSA) and provide a compact and highly intuitive representation of the position-specific amino acid composition of binding motifs, active...... sites, etc. in biological sequences. Accurate generation of sequence logos is often compromised by sequence redundancy and low number of observations. Moreover, most methods available for sequence logo generation focus on displaying the position-specific enrichment of amino acids, discarding the equally...... valuable information related to amino acid depletion. Seq2logo aims at resolving these issues allowing the user to include sequence weighting to correct for data redundancy, pseudo counts to correct for low number of observations and different logotype representations each capturing different aspects...

  13. Solution structure of the two RNA recognition motifs of hnRNP A1 using segmental isotope labeling: how the relative orientation between RRMs influences the nucleic acid binding topology

    Barraud, Pierre; Allain, Frederic H.-T., E-mail: allain@mol.biol.ethz.ch [ETH Zurich, Institute of Molecular Biology and Biophysics (Switzerland)

    2013-01-15

    Human hnRNP A1 is a multi-functional protein involved in many aspects of nucleic-acid processing such as alternative splicing, micro-RNA biogenesis, nucleo-cytoplasmic mRNA transport and telomere biogenesis and maintenance. The N-terminal region of hnRNP A1, also named unwinding protein 1 (UP1), is composed of two closely related RNA recognition motifs (RRM), and is followed by a C-terminal glycine rich region. Although crystal structures of UP1 revealed inter-domain interactions between RRM1 and RRM2 in both the free and bound form of UP1, these interactions have never been established in solution. Moreover, the relative orientation of hnRNP A1 RRMs is different in the free and bound crystal structures of UP1, raising the question of the biological significance of this domain movement. In the present study, we have used NMR spectroscopy in combination with segmental isotope labeling techniques to carefully analyze the inter-RRM contacts present in solution and subsequently determine the structure of UP1 in solution. Our data unambiguously demonstrate that hnRNP A1 RRMs interact in solution, and surprisingly, the relative orientation of the two RRMs observed in solution is different from the one found in the crystal structure of free UP1 and rather resembles the one observed in the nucleic-acid bound form of the protein. This strongly supports the idea that the two RRMs of hnRNP A1 have a single defined relative orientation which is the conformation previously observed in the bound form and now observed in solution using NMR. It is likely that the conformation in the crystal structure of the free form is a less stable form induced by crystal contacts. Importantly, the relative orientation of the RRMs in proteins containing multiple-RRMs strongly influences the RNA binding topologies that are practically accessible to these proteins. Indeed, RRM domains are asymmetric binding platforms contacting single-stranded nucleic acids in a single defined orientation. Therefore, the path of the nucleic acid molecule on the multiple RRM domains is strongly dependent on whether the RRMs are interacting with each other. The different nucleic acid recognition modes by multiple-RRM domains are briefly reviewed and analyzed on the basis of the current structural information.

  14. 人心脏型脂肪酸结合蛋白检测试剂盒的临床评价%Clinical trials of diagnostic kit for heart-type fatty acid-binding protein

    陈平纡; 夏爱祥; 李美芹; 郭广宏; 董振南; 杨福军; 席仲兴; 彭林峰; 张正雷; 陈冬梅; 谢贵林; 蒋知新; 孙玉发

    2012-01-01

    目的 评价人心脏型脂肪酸结合蛋白(H-FABP)检测试剂盒(胶体金法)在急性心肌梗死(AMI)诊断中的价值.方法 采用平行、盲法、对照的对比试验设计,比较其试验产品和对比产品对诊断AMI的敏感性、特异性、准确性.结果 共测定240份临床血液标本.试验产品和对比产品的阳性符合率为100%,阴性符合率为96.15%,总符合率为97.92%.对比产品和试验产品结果不一致的5例标本以临床诊断结果为标准进行验证后,试验产品与临床诊断结果的阳性符合率为100%,总符合率为100%.采用Kappa检验考核两种产品测定结果的一致性,Kappa 指数为0.958.经McNamara's test分析,两产品之间无差异,X2=3.20,P>0.05.结论 试验产品显示出较好的诊断价值,可以作为AMI早期诊断标志物,试验产品与对比产品等效.

  15. Cell type-specific glycosylation of Orai1 modulates store-operated Ca2+ entry.

    Dörr, Kathrin; Kilch, Tatiana; Kappel, Sven; Alansary, Dalia; Schwär, Gertrud; Niemeyer, Barbara A; Peinelt, Christine

    2016-03-08

    N-glycosylation of cell surface proteins affects protein function, stability, and interaction with other proteins. Orai channels, which mediate store-operated Ca(2+) entry (SOCE), are composed of N-glycosylated subunits. Upon activation by Ca(2+) sensor proteins (stromal interaction molecules STIM1 or STIM2) in the endoplasmic reticulum, Orai Ca(2+) channels in the plasma membrane mediate Ca(2+) influx. Lectins are carbohydrate-binding proteins, and Siglecs are a family of sialic acid-binding lectins with immunoglobulin-like repeats. Using Western blot analysis and lectin-binding assays from various primary human cells and cancer cell lines, we found that glycosylation of Orai1 is cell type-specific. Ca(2+) imaging experiments and patch-clamp experiments revealed that mutation of the only glycosylation site of Orai1 (Orai1N223A) enhanced SOCE in Jurkat T cells. Knockdown of the sialyltransferase ST6GAL1 reduced α-2,6-linked sialic acids in the glycan structure of Orai1 and was associated with increased Ca(2+) entry in Jurkat T cells. In human mast cells, inhibition of sialyl sulfation altered the N-glycan of Orai1 (and other proteins) and increased SOCE. These data suggest that cell type-specific glycosylation influences the interaction of Orai1 with specific lectins, such as Siglecs, which then attenuates SOCE. In summary, the glycosylation state of Orai1 influences SOCE-mediated Ca(2+) signaling and, thus, may contribute to pathophysiological Ca(2+) signaling observed in immune disease and cancer.

  16. Discovery and expression of 3 siglecs-like in Oreochromis niloticus neutrophil, and their interaction with group B streptococcal sialylated capsular polysaccharides.

    Dong, Junjian; Wei, Yuanzheng; Ye, Xing; Sun, Chengfei; Tian, Yuanyuan; Lu, Maixin; Du, Juanjuan; Chen, Zhihang

    2016-05-01

    Sialic acid - binding immunoglobulin - like lectins (Siglecs) are members of the largest superfamily of immune receptors; they recognize sialic acid and are mainly expressed in immune cells. Studies on mammals indicate that Streptococcus agalactiae (GBS) evade immune reactions by interacting with the host immune cells via the sialic acid of sialylated capsular polysaccharides. However, it is currently unknown if fish-derived GBS can interact with Siglecs to evade host immunity. In this study, we examined the binding of FITC-GBS with neutrophils to determine the presence of receptors that binds with GBS. Furthermore, 3 Siglec-like genes, (OnSiglec-1-like/-4b-like/-14-like) from the neutrophils cDNA were screened by PCR. All the genes had specific domains (immunostimulation and immunosuppression domains), conserved amino acid residues, and sialic acid polysaccharide binding sites that are found in mammalian Siglecs. Flow cytometry of Siglecs-like/COS-7 cells and ELISA of Siglecs/Ex-Fc fusion proteins confirmed that 3 Siglecs-like have high binding activity with GBS. Erythrocytes adhesion assays and sialylated glycans binding assay confirmed that 3 Siglecs-like bind to sialic acid polysaccharides. Siglecs-like had high expression levels in the spleen, gill, and kidney in Oreochromis niloticus by qPCR. After experimental infection, Siglec-1-like/-14-like showed a significant upregulated initially and later downregulated in liver, spleen, kidney, and gill. However, Siglec-4b-like was downregulated in most tissues, except that in liver. The results indicate that 3 OnSiglecs-like may recognize GBS sialylated capsular polysaccharides. GBS infections led to significant changes in Siglecs-like expression in immune-related tissues. However, immunostimulation or immunosuppression via the recognition of GBS by different Siglecs-like molecules requires additional studies.

  17. Host Immune Responses in HIV-1 Infection: The Emerging Pathogenic Role of Siglecs and Their Clinical Correlates

    Mikulak, Joanna; Di Vito, Clara; Zaghi, Elisa; Mavilio, Domenico

    2017-01-01

    A better understanding of the mechanisms employed by HIV-1 to escape immune responses still represents one of the major tasks required for the development of novel therapeutic approaches targeting a disease still lacking a definitive cure. Host innate immune responses against HIV-1 are key in the early phases of the infection as they could prevent the development and the establishment of two hallmarks of the infection: chronic inflammation and viral reservoirs. Sialic acid-binding immunoglobulin-like lectins (Siglecs) belong to a family of transmembrane proteins able to dampen host immune responses and set appropriate immune activation thresholds upon ligation with their natural ligands, the sialylated carbohydrates. This immune-modulatory function is also targeted by many pathogens that have evolved to express sialic acids on their surface in order to escape host immune responses. HIV-1 envelope glycoprotein 120 (gp120) is extensively covered by carbohydrates playing active roles in life cycle of the virus. Indeed, besides forming a protecting shield from antibody recognition, this coat of N-linked glycans interferes with the folding of viral glycoproteins and enhances virus infectivity. In particular, the sialic acid residues present on gp120 can bind Siglec-7 on natural killer and monocytes/macrophages and Siglec-1 on monocytes/macrophages and dendritic cells. The interactions between these two members of the Siglec family and the sialylated glycans present on HIV-1 envelope either induce or increase HIV-1 entry in conventional and unconventional target cells, thus contributing to viral dissemination and disease progression. In this review, we address the impact of Siglecs in the pathogenesis of HIV-1 infection and discuss how they could be employed as clinic and therapeutic targets.

  18. Human DC-SIGN binds specific human milk glycans.

    Noll, Alexander J; Yu, Ying; Lasanajak, Yi; Duska-McEwen, Geralyn; Buck, Rachael H; Smith, David F; Cummings, Richard D

    2016-05-15

    Human milk glycans (HMGs) are prebiotics, pathogen receptor decoys and regulators of host physiology and immune responses. Mechanistically, human lectins (glycan-binding proteins, hGBP) expressed by dendritic cells (DCs) are of major interest, as these cells directly contact HMGs. To explore such interactions, we screened many C-type lectins and sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed by DCs for glycan binding on microarrays presenting over 200 HMGs. Unexpectedly, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) showed robust binding to many HMGs, whereas other C-type lectins failed to bind, and Siglec-5 and Siglec-9 showed weak binding to a few glycans. By contrast, most hGBP bound to multiple glycans on other microarrays lacking HMGs. An α-linked fucose residue was characteristic of HMGs bound by DC-SIGN. Binding of DC-SIGN to the simple HMGs 2'-fucosyl-lactose (2'-FL) and 3-fucosyl-lactose (3-FL) was confirmed by flow cytometry to beads conjugated with 2'-FL or 3-FL, as well as the ability of the free glycans to inhibit DC-SIGN binding. 2'-FL had an IC50 of ∼1 mM for DC-SIGN, which is within the physiological concentration of 2'-FL in human milk. These results demonstrate that DC-SIGN among the many hGBP expressed by DCs binds to α-fucosylated HMGs, and suggest that such interactions may be important in influencing immune responses in the developing infant.

  19. HLA Typing for Bone Marrow Transplantation

    2011-07-21

    ISBT International Society Blood Transfusion IT Information Technology KIR Killer Immunoglobulin-like Receptor LR Low Resolution mHAg Minor...National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology, and Transplantation NAT Nucleic Acid Test NCI National Cancer ...important research study funded by this grant investigated the allelic diversity of the Killer Immunoglobulin-like Receptor ( KIR ) ligands. During the

  20. NCBI nr-aa BLAST: CBRC-CFAM-01-0026 [SEVENS

    Full Text Available CBRC-CFAM-01-0026 dbj|BAD12829.1| immunoglobulin-like transcript 11 protein [Equus ...caballus] dbj|BAD12830.1| immunoglobulin-like transcript 11 protein [Equus caballus] BAD12829.1 1e-29 59% ...

  1. Gclust Server: 9682 [Gclust Server

    Full Text Available TED: similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding prot...r to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog

  2. Research Advances in Molecular Mechanisms of CD22%CD22分子机制的研究进展

    徐洪来; 肖敏; 刘强(综述); 潘光栋; 陈忠华(审校)

    2015-01-01

    CD22 is type I transmembrane glycoprotein,which is a member of the family of sialic acid-binding immunoglobulin-like lectins.As an inhibitory coreceptor of B cell receptor(BCR),CD22 negatively regulates activating signal of the B cell.CD22 specifically recognizes glycoprotein ligands containing α-2, 6-linked sialic acid.After activation of the BCR by antigen,tyrosine of immunoreceptor tyrosine-based inhibi-tor motirs located in the intracellular tail of the CD22 is rapidly phosphorylated.Then,downstream signaling molecules are activated to dampen BCR signal by reducing calcium ions flux .CD22 could be involved in hom-ing process of B cells.CD22 expresses relatively specially on the surface of B cells ,which makes it an attrac-tive target for regulation of immune response mediated by B cells and targeted therapy for B cell tumors .%CD22为Ⅰ型跨膜糖蛋白,是唾液酸结合免疫球蛋白样凝集素家族成员。作为 B 细胞受体(BCR)的抑制性共受体,CD22对B细胞激活信号具有负性调节作用。 CD22能够与包含α-2,6连接唾液酸的糖蛋白配体特异性结合,抗原激活BCR,也使CD22胞质区免疫受体酪氨酸抑制基序中的酪氨酸迅速磷酸化,并激活下游信号分子抑制钙离子内流而减弱 BCR信号。 CD22参与 B 细胞的归巢过程。因CD22相对特异地表达于B细胞表面,已成为调节 B细胞免疫及治疗某些 B 细胞肿瘤的良好靶标。

  3. Siglec-15 is a potential therapeutic target for postmenopausal osteoporosis.

    Kameda, Yusuke; Takahata, Masahiko; Mikuni, Shintaro; Shimizu, Tomohiro; Hamano, Hiroki; Angata, Takashi; Hatakeyama, Shigetsugu; Kinjo, Masataka; Iwasaki, Norimasa

    2015-02-01

    Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with an immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein, DNAX-activating protein 12kDa (DAP12). Although Siglec-15 has an important role in physiologic bone remodeling by modulating RANKL signaling, it is unclear whether it is involved in pathologic bone loss in which multiple osteoclastogenic factors participate in excessive osteoclastogenesis. Here we demonstrated that Siglec-15 is involved in estrogen deficiency-induced bone loss. WT and Siglec-15(-/-) mice were ovariectomized (Ovx) or sham-operated at 14wk of age and their skeletal phenotype was evaluated at 18 and 22wk of age. Siglec-15(-/-) mice showed resistance to estrogen deficiency-induced bone loss compared to WT mice. Although the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts increased after ovariectomy in both WT and Siglec-15(-/-) mice, the increase was lower in Siglec-15(-/-) mice than in WT mice. Importantly, osteoclasts in Siglec-15(-/-) mice were small and failed to spread on the bone surface, indicating impaired osteoclast differentiation. Because upregulated production of TNF-α as well as RANKL is mainly responsible for estrogen deficiency-induced development of osteoclasts, we examined whether Siglec-15 deficiency affects TNF-α-induced osteoclastogenesis in vitro. The TNF-α mediated induction of TRAP-positive multinucleated cells was impaired in Siglec-15(-/-) cells, suggesting that Siglec-15 is involved in TNF-α induced osteoclastogenesis. We also confirmed that signaling through osteoclast-associated receptor/Fc receptor common γ chain, which is an alternative ITAM adaptor to DAP12, rescues multinucleation but not cytoskeletal organization of TNF-α and RANKL-induced Siglec-15(-/-) osteoclasts, indicating that the Siglec-15/DAP12 pathway is especially important for cytoskeletal

  4. Progress in the research of CD33rSiglecs%CD33相关的唾液酸结合免疫球蛋白类凝集素研究进展

    陈小军; 廖晓龙

    2008-01-01

    CD33相关的唾液酸结合免疫球蛋白类凝集素CD33rSiglecs是Siglecs家族的一员.Siglecs家族能够介导唾液酸依赖的细胞间相互作用,并且有可能在信号传导中起重要作用.唾液酸黏附素、CD22、CD33和髓鞘相关糖蛋白及一些CD33rSiglecs成员已经被克隆.鉴于它们表达于免疫细胞的特性,人们已经在靶向治疗上对它们给予了足够的重视,但是这些凝集素是如何被调节进而发挥其功能的,人们仍知之甚少.之前对于唾液酸凝集素、CD22、CD33的研究表明它们的糖基化对于它们与其配体结合起重要作用.%CD33rSiglecs (CD33-related sialic acid binding immunoglobulin-like lectins)are members of the Siglecs family which mediate sialic acid-dependent cellular interactions and may some cases play important role in signal transduction. In addition to the previously characterized Siglecs, sialoabdesins, CD22, CD33, myelin-associated glycoprotein and several CD33rSiglecs have recently been cloned. Although these novel re-ceptors have gained considerable interest as therapeutic targets because of their expression on immune cells, very little is known about the activities of these lectins and how they are regulated. Previous studies on sialoadhesin, CD22 and CD33 have shown that Siglec glycosylation has significant effects on the binding to the their ligands. In this review, we summarized the recent research results about CD33rSiglecs members on protein sequences, ligand patterns, gene structures, expression patterns and function.

  5. 凝血酶-抗凝血酶复合物及肠脂肪酸结合蛋白检测在早期诊断肠系膜上动脉栓塞的实验研究%Earlier diagnosis for superior mesenteric artery embolism by detection of thrombin-antithrombin complex and intestinal fatty acid binding protein:an animal experiment

    张义雄; 刘智龄; 宋偲婷; 刘晓亮; 张兴文; 隆艳飞; 肖斌

    2015-01-01

    目的:观察凝血酶-抗凝血酶复合物(TAT)、肠脂肪酸结合蛋白(IFABP)在肠系膜上动脉栓塞(SMAE)模型犬外周血含量的变化,探讨SMAE的早期诊断指标.方法:自体血栓栓塞法建立SMAE动物模型,酶联免疫法检测犬外周血TAT、IFABP及D-二聚体(DD)含量,自动生化分析仪测乳酸脱氢酶(LDH).结果:栓塞后30 min,SMAE组TAT值、IFABP值均明显升高,与正常对照组比较,差异有统计学意义,但与假手术组比较,TAT值栓塞前1h差异无统计学意义,各时间点的IFABP值差异均有统计学意义.SMAE犬外周血DD值、LDH值也明显升高,但升高时间迟于TAT和IFABP.检验效能分析显示:联合TAT和IFABP检测可保持较高的诊断敏感度,并提高诊断特异性.结论:TAT、IFABP可能作为SMAE的早期诊断指标,但需将二者联合检测,以提高诊断特异性.

  6. 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

    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.

  7. 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

    邹艳慧; 高学文; 王萍; 云雅丽

    2012-01-01

    目的 探讨小肠型脂肪酸结合蛋白(FABP2)外显子2第54位密码子的基因多态性与不同民族冠心病患者血脂水平的关系.方法 收集入选人群的空腹外周血标本,全血用于提取DNA,血清用于检测血脂.采用聚合酶链反应(PCR),DNA限制性内切酶酶切(RFLP)等技术,分别对病例组(汉族冠心病组60例,蒙古族冠心病组60例)和对照组(汉族对照组51例,蒙古族对照组51例)54A/T FABP2 基因型进行分析.结果 (1)汉族冠心病组人群54T等位基因频率为0.542,54A等位基因频率为0.458;蒙古族冠心病人群54T等位基因频率为0.708,54A等位基因频率为0.292;汉族对照组人群54T等位基因频率为0.284,54A等位基因频率为0.716;蒙古族对照组人群54T等位基因频率为0.353,54A等位基因频率为0.647;与对照组相比:汉族及蒙古族冠心病组人群突变型54T等位基因频率明显增高,且差异均有统计学意义(统计值分别为:x2=14.967,P<0.05;x2=28.083,P<0.05);蒙古族冠心病人群突变型54T等位基因频率较汉族冠心病人群增高,且差异有统计学意义(x2=7.111,P<0.05).(2)与FABP2 Thr54(-)者相比,冠心病组FABP2Thr54(+)者的空腹血浆TG[汉族冠心病:Thr54(-)人群为(1.89 ±0.57) mmol/L,Thr54(+)人群为(3.92±1.63) mmol/L,P=0.001;蒙古族冠心病组:Thr54 (-)人群为(2.23 ±0.13) mmol/L,Thr54(+)人群为(4.03±1.14)mmol/L,P=0.035]、低密度脂蛋白胆固醇[汉族冠心病:Thr54(-)人群为(3.09±0.92) mmol/L,Thr54(+)人群为(4.05±1.14) mmol/L,P=0.025;蒙古族冠心病组:Thr54(-)人群为(4.26±0.08) mmol/L,Thr54(+)人群为(5.10 ±0.56)mmol/L,P=0.045]水平升高.结论 (1)内蒙古自治区呼和浩特市市区蒙古族及汉族人群中存在FABP2外显子2第54位密码子的基因多态性.(2)FABP2基因多态性是冠心病患者脂质代谢异常的影响因素,可能与冠心病发病风险有关,携带FABP2 Thr基因的蒙古族个体冠心病发病风险增高.%Objective To 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 polymorphism in urban Mongolian and Han population.Gene mutation frequency is in accordance with Hardy-Weinberg law of genetic equilibrium,suggesting the sample group representative.(2) FABP2 polymorphism may have a certain contribution to dyslipidemia in patients with coronary heart disease.FABP2 gene polymorphism may be associated with coronary heart disease.Individuals of Mongolian with FABP2 Thr54( + ) has a higher risk of coronary heart disease.

  8. 先天性心脏病介入封堵术前后血清心肌型脂肪酸结合蛋白水平的变化及其影响因素分析%Changes of serum heart-type fatty acid binding protein level after interventional occlusion for congenital heart diseases and analysis of its influence factors

    张燕; 李靖; 李莉; 关怀敏

    2009-01-01

    线性回归分析显示病理类型、年龄、手术时间、封堵器释放次数是影响术后血清H-FABP水平的主要因素(β分别为0.666,-0.460,0.589,0.483,P均<0.05).结论:先天性心脏病介入封堵术可引起可逆性的心肌微损伤,血清H-FABP水平升高程度与病理类型、年龄、手术时间、封堵器释放次数有关.

  9. Serum adipocyte-fatty acid binding protein: an important marker of abdominal obesity in adolescents%血清脂肪细胞脂肪酸结合蛋白:青少年腹型肥胖的重要标志物

    黄岚; 董萍; 吴鸿; 王海鹰; 陈月; 邹大进

    2009-01-01

    BP浓度与BMI、腰围、腰臀比、收缩压、舒张压、HOMA-IR、FINS、2hPG、尿酸、总胆同醇、TG、LDL-C呈直线相关,随着代谢综合征组分数目的 增加A-FABP水平进行性增加.结论 血清A-FABP表达升高与青少年腹型肥胖、糖脂代谢紊乱密切相关,是青少年不良肥胖及代谢综合征发生发展的重要标志物.%rs of glucose and lipid metabolism in adolescents with abdominal obesity. Determimation of serum A-FABP concentration might be useful in diagnosis and prevention of metabolic syndrome and abdominal obesity in adolescent.

  10. 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

    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.

  11. 心脏型脂肪酸结合蛋白敏感性在急性冠脉综合征早期诊断中的作用%The sensitivity of heart type fatty acid binding protein in the early diagnosis of acute coronary syndrome

    孙猛; 柳克晔; 刘福林; 周晓东; 韩喆; 周程

    2011-01-01

    目的 通过检测急性冠脉综合症患者心脏型脂肪酸结合蛋白(H-FABP),并与肌钙蛋白(cTnI)做对比,探讨H-FABP的敏感性对急性冠脉综合征的早期诊断价值.方法 ACS患者105例在胸痛发作3h、6h、12h 3个时间点采血测定H-FABP、cTnI,观察其水平变化情况并做比较.同时取20例健康志愿者作为对照组.结果 病例组H-FABP 3h(11.62±3.4)μg/L,6h(18.6±5.1)μg/L,12h(6.67±4.7)μg/L均明显高于对照组的(4±2.7)μg/L,差异有统计学意义(P<0.05).病例组中胸痛发作3h H-FABP灵敏度为63.8%,cTnI灵敏度为95.24%;胸痛6h H-FABP的灵敏度为95%,cTnI灵敏度为13.3%;胸痛12h H-FABP灵敏度为40%,cTnI灵敏度为46.2%,在胸痛发作3h和6h 2个时间点H-FABP灵敏度明显高于cTnI灵敏度;胸痛发作12h H-FABP灵敏度与cTnI相似.结论 应用H-FABP的敏感性可对急性心肌缺血损伤做出早期诊断,在循环中出现的时间及达到高峰的时间明显早于cTnI,在胸痛时间6h以内,H-FABP比cTnI敏感,能够提高对ACS的早期诊断效率.

  12. Effect of continuous renal replacement therapy on expression of liver-type fatty acid binding proteins (L-FABP) in severe sepsis patients with acute kidney injury%连续性肾脏替代治疗对急性肾损伤患者尿肝型脂肪酸结合蛋白表达的影响

    郝晓萍; 邬碧波; 张黎明; 唐琦; 牛开亚; 承解静

    2016-01-01

    目的 观察连续性肾脏替代治疗(continuous renal replacement herapy,CRRT)对严重脓毒症急性肾损伤(acute kidney injury,AKD患者肝型脂肪酸结合蛋白表达水平的影响.方法 确诊严重脓毒症AKI患者68例,分为常规药物治疗组(A组,n=33例)和CRRT组(B组,n=35例).2组均在确诊严重脓毒症后,立即给予规范的抗脓毒症治疗(按照2012年SCC标准),B组在规范治疗的基础上同步行CRRT 24h.2组均监测0h、12h、24h及48h血肌酐(serum creatinine,sCr)、血L-FABP(serum L-FABP,sL-FABP)、尿L-FABP (urine L-FABP,uL-FABP)水平,同时监钡B组CRRT废液中L-FABP的表达水平.记录28天病死率.结果 A组sL-FABP水平在治疗后48h显著高于治疗前[(1328±101) μg/(g ·Cr)比(700±88)μg/(g·Cr),t=5.435,P<0.02)],而B组治疗后48h与治疗前比较sL-FABP水平改变不明显[(680±74) μg/(g·Cr)比(712±82) μg/(g·Cr),t=1.682,P>0.05)];A组uL-FABP水平治疗后48h改变不明显[(1428±124) μg/(g·C)比(1082±89) μg/(g·C),t=4.854,P>0.05)],B组在CRRT治疗后48h uL-FABP水平较治疗前显著下降,(1324±123) μg/(g·C)比(1978±88) μg/(g·C),t=2.654,P<0.02).B组在CRRT治疗48h,sL-FABP水平与A组同期比较显著降低[(680±32) μg/(g·Cr)比(1328±101) μg/(g·Cr),t=3.028,P=0.042],uL-FABP水平与A组同期比较显著下降[(1324±123) μg/(g·Cr)比(1428±124)μg/(g·Cr),t=12.856,P=0.022],sCr水平与A组同期比较显著下降[(115±12)μmol/L比(295±32) μmol/L,t=8.256,P=0.032].B组超滤液中未检测出L-FABP表达.结论 CRRT能降低uL-FABP的表达,改善AKI的预后,但并非通过直接清除血中的L-FABP途径.uL-FABP水平可作为CRRT疗效判断的可靠指标.

  13. 急性心肌梗死心肌型脂肪酸结合蛋白与心脏事件的相关性%Relationship between heart fatty acid binding protein and clinical prognosis in patients of acute myocardial infarction

    张跃明; 颜永进

    2005-01-01

    目的:探讨心肌型脂肪酸结合蛋白(H-FABP)与急性心肌梗死(AMI)患者预后的关系.方法:正常对照组20例,急性心肌梗死组58例经住院期间及平均6个月的随访,观察H-FABP的变化及心血管事件发生组与未发生组的差异.结果:血清H-FABP对照组为4.2±2.3μg/L,AMI组为16.2±3.6μg/L,总心血管事件发生组为19.9±4.5μg/L,未发生组为15.8±4.9μg/L.结论:AMI急性期血H-FABP浓度显著增高,随访心血管事件发生率高的患者其H-FABP明显升高,H-FABP可作为AMI心血管事件的预测因子.

  14. 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

    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 ). Conclusion The plasma H-FABP levels in APE patients with APE is increased, which decrease after effertive treatment, which may be helpful in the diagnosis and effectiveness evaluation oi APE.

  15. 心肌型脂肪酸结合蛋白测定正常参考值的初步研究%The Preliminary Study on the Plasma Normal Reference Value of Heart-type Fatty Acid-binding Protein

    衣志勇; 李小鹰; 孙宇; 蒋知新; 王显花; 任建伟

    2004-01-01

    目的初步了解国人血清心肌型脂肪酸结合蛋白(H-FABP)正常参考值.方法用作者建立的H-FABP酶联免疫吸附法(ELISA)检测126人健康人血清心肌型脂肪酸结合蛋白,并同时进行心肌肌酸激酶同工酶(CK-MB)、血浆肌钙蛋白I(cTnI)、血浆肌红蛋白(Myo)测定做对照.H-FABP正常参考值上限按均值+2×标准差(±2s)计算.结果正常H-FABP血清浓度为3.79±3.52μg/L,性别及年龄差异无显著性意义.结论国人血清H-FABP正常参考值为0~10.83μg /L.

  16. Relationship between the transcription of endogenous liver-fatty acid binding protein and differentiation of stem cells in the developing gut%内源性肝脂肪酸结合蛋白基因与肠道干细胞分化发育的关系

    常晓彤; 王振辉; 付小兵

    2003-01-01

    目的探讨内源性肝脂肪酸结合蛋白基因( L-fabp)在转录水平的表达与小肠干细胞增生分化的时空关系.方法利用免疫组织化学、原位杂交和反转录聚合酶链反应( RT-PCR)等技术,分别检测胚胎期 E14 d, E17 d, E19 d和幼鼠期 P1 d, P2 d, P7 d, P28 d大鼠小肠上皮细胞增殖细胞核抗原( PCNA)、 L-fabp mRN水平及其定位分布.结果胎鼠 E19 d,小肠细胞内 L-fabp基因开始转录 mRNA为( 2.8± 0.23)%.到幼鼠期 P2 d L-fabp mRNA水平达到最高峰为( 6.31± 0.24)%,与 E19 d比较差异具有非常显著性的意义( P< 0.001,t=8.411).幼鼠 P1 d、 P7 d、 P14 d、 P28 d期, L-fabp mRNA水平有所减少,分别为( 4.2± 0.25)%,( 3.89± 0.23)%,( 3.3± 0.26)%,( 3.36± 0.23)%.与 E19 d比较差异有显著性意义( P< 0.05,t=2.754,2.671,2.167,2.243); L-fabp mRNA原位杂交定位分析显示, E19 d少量阳性细胞开始出现于绒毛顶部,阳性率约为 1%.从 P1 d~ P28 d, L-fabp mRNA阳性细胞表达率不断升高,阳性率分别为 12%, 45%, 65% , 89%,并且分布范围从绒毛顶部向下逐渐扩大,而小肠隐窝底部细胞始终为阴性.与此相反,从 P14 d到 P28 d, PCNA阳性细胞逐渐减少;到 P28 d,阳性细胞只局限于隐窝内细胞.结论肠道干细胞发育分化过程中,内源性 L-fabp基因 mRNA水平的变化,可能与 L-fabp参与细胞分化成熟过程中磷脂膜构建及脂肪酸吸收、β氧化功能有关,提示细胞内源性 L-fabp转录水平的表达可作为肠道干细胞分化过程中磷脂膜构建及脂肪酸吸收、β氧化功能有关,提示细胞内源性 L-fabp转录水平的表达可作为肠道干细胞分化成熟的标志.

  17. The value of heart-type fatty acid-binding protein and cTnI、CK、Mb、CK-Mb in early ACS%H-FABP联合cTnI、CK、Mb、CK-Mb检测在ACS早期诊断中的价值

    谢明水; 刘国政; 李玲; 敖晶晶; 刘杨; 张振建

    2013-01-01

    目的:探讨H-FABP与cTnI、CK、Mb、CK-Mb联合检测在急性冠脉综合征患者诊断中的临床价值.方法:采用ELISA法检测81例6h内胸痛发作患者的血清H-FABP水平,采用免疫荧光法测定这些患者血清中的cTnI、CK、Mb、CK-Mb,其中急性心肌梗死(AMI)30例、不稳定型心绞痛(UAP) 26例、非心源性胸痛(NCCP)25例,同期选择27例健康体检者为对照组.应用Logistic回归模型绘制ROC曲线并计算曲线下面积(AUC)来评估H-FABP的诊断价值.结果:AMI组的H-FABP水平(73.35±56.73) μg/L最高,UAP组(13.50±5.64)μtg/L次之(P<0.01);NCCP组(4.07±3.27) μg/L与对照组(3.42±1.53) μg/L比较差异无统计学意义(P>0.05).H-FABP诊断AMI敏感性(96.7%)明显优于cTnI诊断敏感性74.5%(P<0.05);H-FABP与cTnI联合检测ROC曲线下面就更高达0.908.结论:H-FABP与cTnI联合检测可为急性冠脉综合征患者的诊断提供依据.

  18. 非酒精性脂肪肝患者血清肝型脂肪酸结合蛋白检测的临床意义%Detecting liver fatty acid binding protein(L-FABP) in serum of human nonalcoholic fatty liver disease (NAFLD) and its clinical significance

    任哲; 任江南

    2014-01-01

    目的 探讨非酒精性脂肪肝(NAFLD)患者血清肝型脂肪酸结合蛋白(L-FABP)变化及其临床意义.方法 用ELISA法测定90例NAFLD患者血清L-FABP的变化,同时计算体重指数(BMI),腰臀比(WHR);肝功能(丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(γ-GT));血脂(总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C));空腹血浆葡萄糖(FBG)和胰岛素抵抗指数(HOMA-IR).并与健康对照组(n=80)进行比较.结果 NAFLD组的血清L-FABP明显高于健康对照组(P<0.01)且与NAFLD严重程度有关;NAFLD组BMI、WHR、FBG、HOMA-IR、AST、γ-GT、TG、LDL-C水平明显高于健康对照组(P<0.05),血清HDL-C水平明显低于健康对照组(P<0.05);L-FABP与BMI(r=0.7365)、WHR(r=0.6713)、FBG(r=0.6368)、HOMA-IR(r=0.6539)、AST(r=0.6640)、γ-GT(r=0.6768)、TG(r=0.7012)、LDL-C(r=0.6034)呈正相关(P<0.01),与HDL-C(r=-0.6839)呈负相关(P<0.01).结论 L-FABP可能参与NAFLD发病机制的发生与发展过程,随着对L-FABP研究和认识的深入,血清L-FABP可能成为NAFLD的临床病情观察的新指标,并为药物靶向治疗提供新思路.

  19. 人心型脂肪酸结合蛋白(H-FABP)的原核表达、纯化和冻干品的制备%The Expression and Purification of Human Heart-type Fatty Acid Binding Protein and Preparation of Lyophilized Protein

    武建伟; 才蕾; 任艳娜; 钱伟; 王继华; 唐时幸

    2014-01-01

    目的:获得重组人心型脂肪酸结合蛋白,分析其活性及制备冻干品.方法:从GenBank中检索人源H-FABP CDs序列,合成基因后构建原核表达载体pET-28a(+)-H-FABP.将表达载体转入E.coli BL21(DE3),摸索pET-28a(+)-H-FABP最佳诱导条件,表达并纯化重组蛋白.使用检测试剂检测纯化后的重组H-FABP活性,研究最佳冻干方案并考察冻干品的稳定性.结果:经过优化诱导条件,重组H-FABP在BL21(DE3)中以可溶性蛋白形式表达.诱导条件为OD600≈0.6,IPTG终浓度0.4mmol/L,30℃诱导4h.通过Ni2+亲和层析纯化可得到纯度大于95%的重组H-FABP蛋白.重组H-FABP冻干品可以在37℃稳定保存12d,25℃、4℃稳定保存至少4个月.结论:本项研究中的重组H-FABP表达体系成熟、蛋白活性高,冻干品稳定性好,为后续研究提供了稳定高效的生物原材料.

  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

    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

    目的 探讨近曲小管肝型脂肪酸结合蛋白(L-FABP)对骨髓移植诱导的小鼠IgAN的肾脏保护作用.方法 通过骨髓移植在肾小管高表达人类L-FABP(hL-FABP)基因的转基因鼠(Tg)和相同背景的野生鼠(WT)上重建IgAN.受体鼠分别在骨髓移植后第6和12周处死,留取肾脏标本.用实时荧光定量PCR方法检测肾脏hL-FABP、纤连蛋白(FN)和单核细胞趋化蛋白1(MCP-1)的mRNA表达;免疫组化法检测hL-FABP和FN的蛋白表达分布;Western印迹法检测hL-FABP、4-羟壬烯醛(4-HNE)、血红素加氧酶1(HO-1)、FN、Ⅳ型胶原的蛋白表达水平;ELISA法检测血清IgA、尿白蛋白和尿hL-FABP水平.结果 骨髓移植在受体转基因鼠(Tg-ddY)和野生鼠(WT-ddY)上均重建了IgAN,血清IgA水平升高伴有系膜区IgA沉积,组间差异无统计学意义.正常Tg鼠的肾小管表达hL-FABP.与正常Tg鼠相比,骨髓移植后第6周,Tg-ddY鼠肾脏hL-FABP的mRNA(1.62±0.32比0.46±0.09,P<0.01)和蛋白(1.74±0.76比1.14±0.31,P<0.01)表达水平显著上调,伴有尿hL-FABP水平(μg/g肌酐)显著升高(59.87±26.75比31.01±14.86,P<0.05).与Tg-ddY鼠相比,WT-ddY鼠在第12周出现明显的白蛋白尿(mg/L)(828±656比82±22,P<0.01)、明显的系膜基质扩张(P<0.01),并在肾小球出现更多的FN及Ⅳ型胶原沉积.Tg-ddY鼠的肾脏HO-1和4-HNE修饰蛋白(均P<0.05)以及MCP-1 mRNA的表达(P<0.01)被显著抑制.结论 肾小管L-FABP可能通过抑制氧化应激和炎性介质的产生减轻肾小球损伤,在IgAN早期发挥了肾脏保护作用.%Objective To investigate the renoprotection of tubular L-FABP in murine IgA nephropathy (IgAN) induced by bone marrow transplantation(BMT). Methods IgAN models were reconstituted by BMT from IgAN-prone mice into mice (Tg) transgenically tubular overexpressing human L-FABP (hL-FABP) and wild type (WT) mice. These recipients were sacrificed at 6 and 12 weeks after BMT and their kidneys were collected. The expressions 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. The association of epidermal fatty acid binding protein with obesity, metabolic syndrome and cardiovascular dis-eases in children%血清上皮型脂肪酸结合蛋白与儿童肥胖、代谢综合征及其心血管危险因素的相关性研究

    武明雷; 刘戈力; 杨箐岩; 郝利苹; 鲍鹏丽; 姜丽红; 郑荣秀

    2013-01-01

    目的:探讨血清上皮型脂肪酸结合蛋白(E-FABP)与肥胖儿童心血管疾病危险因素的相关性。方法入选30例代谢综合征(MS)儿童,32例非MS肥胖儿童以及50例正常对照儿童,检测并比较其E-FABP水平、糖脂代谢指标等的差异。结果与对照组相比较,MS组血清E-FABP水平升高,差异具有统计学意义(P=0.001);与非MS肥胖组相比,MS组血清E-FABP水平有升高趋势,但差异无统计学意义(P>0.05)。血清E-FABP水平与腰臀比、腰高比、动脉粥样硬化指数、空腹胰岛素、胰岛素抵抗指数呈正相关(P0.05). The cor-relations of E-FABP with waist to hip ratio, waist-to-height ratio, atherogenic index, fasting insulin, insulin resistance index were positive (P<0.05). According to the multivariate stepwise regression analysis, E-FABP was the independent risk of atherogenic index (P=0.018). Conclusions E-FABP plays a role in the development of atherosclerosis in obesity and MS.

  2. Correlation of Urinary Liver-Type Fatty-acid Binding Protein with Progression of Chronic Kidney Disease%尿肝型脂肪酸结合蛋白与慢性肾脏病进展的关系研究

    曾学辉; 李忠新; 韩鹏勋; 张春雷; 宋林立

    2015-01-01

    目的 探讨尿肝型脂肪酸结合蛋白(L-FABP)与慢性肾脏病进展的关系.方法 选取149例慢性肾脏病患者,使用简化的MORD公式估计的肾小球滤过率对其进行CKD分期,以67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,同时检测尿肌酐、肾功能、肝功能、血红蛋白(Hb)和尿蛋白等指标,并进行统计分析.结果 随着慢性肾病病程进展,患者尿L-FABP水平逐渐上升,亚组比较显示,CKD1期组尿L-FABP水平高于健康对照组(P<0.05),CKD2期组尿L-FABP水平高于CKD1期组(P<0.01),CKD3期组尿L-FABP水平高于CKD2期组(P<0.01),CKD4期组尿L-FABP水平高于CKD3期组(P<0.01),CKD5期组尿L-FABP水平高于CKD4期组(P<0.01).尿L-FABP水平与eGFR呈负相关(r=-0.742,P<0.05),尿L-FABP水平与Scr呈正相关(r=0.836,P<0.05).结论 尿L-FABP水平不仅可早期预测慢性肾脏病的发生,还可监测慢性肾脏病的进展.

  3. 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

    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周剂量加倍,直至达目标靶剂量10 mg或耐受最大剂量。两组患者疗程均为6个月。观察两组患者治疗后临床有效率,应用心脏超声测量治疗前后左心室舒张末内径(LVEDD)、左室射血分数(LVEF)、收缩压(SBP)和舒张压(DBP)变化;结合放射免疫方法测定血浆中BNP和H-FABP浓度变化。结果:治疗后,卡维地洛组患者临床总有效率(96.4%)高于比索洛尔组(89.2%),差异有统计学意义(P<0.05);两组患者治疗后LVEDD、LVEF、BNP、H-FABP、SBP和DBP较治疗前均有明显降低,且卡维地洛组显著低于比索洛尔组,差异均有统计学意义(P<0.01或P<0.05)。结论:卡维地洛与比索洛尔均能明显改善患者心功能,卡维地洛疗效更为显著,同时H-FABP治疗前后的明显下降提示H-FABP也可以作为判断心力衰竭治疗效果的另一个可靠的指标。

  4. 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

    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.

  5. 饲粮脂肪水平对冬毛期银狐生长性能、体脂肪酸组成及空肠中小肠型脂肪酸结合蛋白表达的影响%Effects of Dietary Fat Level on Growth Performance, Body Fatty acid Composition and the Expression of Intestinal Fatty Acid Binding Protein in Jejunum of Silver Foxes during Winter Fur-Growing Period

    张婷; 钟伟; 罗婧; 周宁; 黄健; 王卓; 孙皓然; 樊燕燕; 李光玉

    2015-01-01

    为研究饲粮脂肪水平对冬毛期银狐生长性能、体脂肪酸组成及空肠中小肠脂肪酸结合蛋白( I-FABP)表达的影响,选取145日龄、体重相近的健康雄性银狐50只,随机分成5组(每组10个重复,每个重复1只) ,分别饲喂含10%、12%、16%、20%、24%混合油脂(鸡油:豆油=1:1)的试验饲粮,试验饲粮实测脂肪水平分别为12. 85%( A 组)、14. 71%( B 组)、18. 72%( C 组)、22.23%( D组)、26.11%( E组). 预试期为15 d,正试期为75 d. 结果显示:1)饲粮脂肪水平显著影响冬毛期银狐的平均日采食量( ADFI) ( P0.05). 3)饲粮脂肪水平对银狐皮下腹部脂肪中SFA、MUFA和PUFA的比例无显著影响( P>0.05). 4)随饲粮脂肪水平的升高,空肠中I-FABP mRNA的相对表达量呈上升趋势,表现为E组显著高于A、B、C组(P0.05) . 3) Dietary fat level had no significant effects on the proportion of SFA, MUFA and PUFA of subcutaneous fat of silver foxes ( P>0.05) . 4) The relative expression of I-FABP mRNA in jejunum was in-creased with the dietary fat level increasing, and it showed that group E was significantly higher than groups A, B and C ( P<0.05) . In conclusion, the silver foxes have the best growth performance when fed diets with 18.72% fat during winter fur-growing period;body fatty acid composition of silver foxes reflect the dietary fat-ty acid composition, the fatty acid composition of intermuscular fat is affected by dietary fat level, while the fatty acid composition of subcutaneous fat is stable;moreover, increasing dietary fat level can improve the ex-pression of I-FABP in jejunum of silver foxes during winter fur-growing period.

  6. Changes and implication of serum heart type fatty acid binding protein, high-sensitivity C-reactive protein in patients with obstructive sleep apnea hypopnea syndrome%阻塞性