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Chronic stress sensitizes rats to pancreatitis induced by cerulein:Role of TNF-α 被引量:7
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作者 Marcelo G Binker Andres A Binker-Cosen +3 位作者 Daniel Richards Herbert Y Gaisano Rodica H de Cosen Laura I Cosen-Binker 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第44期5565-5581,共17页
AIM:To investigate chronic stress as a susceptibility factor for developing pancreatitis,as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer.METHODS:Rat pancreatic acini were used to analyze the infl... AIM:To investigate chronic stress as a susceptibility factor for developing pancreatitis,as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer.METHODS:Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation.Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats.RESULTS:In vitro exposure of pancreatic acini toTNF-α disorganized the actin cytoskeleton.This was further increased by TNF-α/CCK treatment,which additionally reduced amylase secretion,and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner.TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release,induced ATP loss,and augmented the ADP/ATP ratio.In vivo,rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels.Serum,pancreatic,and lung inflammatory parameters,as well as caspases' activity in pancreatic and lung tissue,were substantially enhanced in stressed/cerulein-treated rats,which also experienced tissues' ATP loss and greater ADP/ATP ratios.Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema,hemorrhage and leukocyte infiltrate,and pancreatic necrosis.Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-αantibody,which diminished all inflammatory parameters,histopathological scores,and apoptotic/necrotic markers in stressed/cerulein-treated rats.CONCLUSION:In rats,chronic stress increases susceptibility for developing pancreatitis,which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. 展开更多
关键词 PANCREATITIS STRESS Tumor necrosis factor-α
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氯离子通道CFTR: 新靶点
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作者 杨宝学 N.D.Sonawane +2 位作者 赵丹 Stefan Somlo A.S.Verkman 《中国药理通讯》 2008年第2期18-19,共2页
常染色体显性多囊肾病(ADPKD)是一以肾内多发性囊泡为特征的遗传性疾病。发病率为1/1000到1/600。病变损伤肾功能,可导致继发性高血压,肾衰。目前尚无根治多囊肾疗法。病程晚期需进行肾透析或肾移植。多囊肾病人肾脏内囊泡形成的... 常染色体显性多囊肾病(ADPKD)是一以肾内多发性囊泡为特征的遗传性疾病。发病率为1/1000到1/600。病变损伤肾功能,可导致继发性高血压,肾衰。目前尚无根治多囊肾疗法。病程晚期需进行肾透析或肾移植。多囊肾病人肾脏内囊泡形成的详细机制目前虽不清楚,但囊泡的生长涉及囊泡上皮细胞的增生和囊泡内液体分泌。 展开更多
关键词 氯离子通道 CFTR 多囊肾 治疗方法
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有或无糖尿病的患者中微量白蛋白尿与冠心病之间的关系
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作者 Sukhija R. Aronow W.S. +2 位作者 Kakar P. J.L. Mehta 刘相飞 《世界核心医学期刊文摘(心脏病学分册)》 2007年第1期9-10,共2页
众所周知,无论患者有无糖尿病(DM),微量白蛋白尿(MA)都是冠心病(CAD)的危险因素。MA与较高的心血管病死亡率相关,尤其是对于DM患者。然而,少有资料报道血管造影所示CAD病变严重程度与MA之间的关系。
关键词 微量白蛋白尿 病变严重程度 心血管病死亡率 空腹血糖水平 血红蛋白水平 冠状动脉造影 血管造影 高胆
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Characterization of VAMP-2 gene from marine teleostean,Lateolabrax japonicus 被引量:1
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作者 Gaisano Herbert 《Science China(Life Sciences)》 SCIE CAS 2006年第6期591-596,共6页
The whole length SPV2 gene of 715 bp, encoding VAMP-2 protein of 110 amino acids from Japanese sea perch, Lateolabrax japonicus, was obtained by using both RT-PCR; anchored PCR strategies while we initiated the struct... The whole length SPV2 gene of 715 bp, encoding VAMP-2 protein of 110 amino acids from Japanese sea perch, Lateolabrax japonicus, was obtained by using both RT-PCR; anchored PCR strategies while we initiated the structural; functional study on SNARE proteins in marine teleostean. Analysis of the deduced amino acid sequence indicated that SPV2 has its core arginine residue, a potential N-linked glycosylation site near its N-terminal,; one transmembrane domain in its C-terminal. Advanced structural analysis of bioinformatics approach predicts a coiled-coil α-helix backbone as the characteristic of SPV2 main conformational structure, identical to the structure of rat VAMP-2 obtained by crystallography. Semi-quantitative RT-PCR revealed that SPV2 was generally expressed in 10 neural; non-neural tissues, with the highest concentration in brain; the least in muscle. 展开更多
关键词 LATEOLABRAX japonicus VAMP-2 SNARE cloning SEQUENCE analysis.
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花鲈(Lateolabrax japonicus)VAMP-2基因的特征研究
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作者 陈魁 黄晓航 +1 位作者 包振民 Gaisano Herbert 《中国科学(C辑)》 CSCD 北大核心 2006年第4期334-339,共6页
应用反转录PCR和锚定PCR方法克隆了全长715个碱基的花鲈(Lateolabrax japonicus)SPV2基因,证明其编码110个氨基酸的VAMP-2蛋白.运用生物信息学研究工具进行的一级结构分析显示:SPV2蛋白含有SNARE基序及其核心精氨酸残基,其序列N端有一N... 应用反转录PCR和锚定PCR方法克隆了全长715个碱基的花鲈(Lateolabrax japonicus)SPV2基因,证明其编码110个氨基酸的VAMP-2蛋白.运用生物信息学研究工具进行的一级结构分析显示:SPV2蛋白含有SNARE基序及其核心精氨酸残基,其序列N端有一N-糖肽键的糖基化位点,C端有一跨膜结构域.高级结构预测揭示SPV2蛋白的主要空间构象是一个组成SNARE基序的α螺旋卷曲骨架,其主要细节都与X晶体衍射方法得到的大鼠VAMP-2结构相一致.半定量PCR结果表明:在mRNA水平上,VAMP-2基因在鱼体各组织中广泛表达,其中以脑组织最为突出,而肌肉组织则相对最少. 展开更多
关键词 花鲈 VAMP-2蛋白 SNARE蛋白 生物信息学分析
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