Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

AIM： To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase（eNOS） expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 （Hsp90）, as well as by the modifications of calmodulin binding to eNOS. METHODS： Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats. RESULTS： Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length （and the severity） of the disease. Because coimmunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast, drrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity. CONCLUSION： In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide （NO） production is significantly decreased by two mechanisms： a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

瞄准：决定胆汁性肝硬变是否能在内皮的氮的氧化物 synthase (eNOS ) 导致象修正那样的胰腺的机能障碍表达式并且 eNOS 的规定是否能被规章的蛋白质 caveolin 改变并且加热吃惊蛋白质 90 (Hsp90 ) ，以及由对 eNOS 有约束力的 calmodulin 的修正。方法：Immunoprecipitations 和西方的弄污分析在从假冒、肝脏硬化症的老鼠孤立的胰被执行。结果：胰腺的损害在肝脏硬化症的老鼠是次要的，但是 eNOS 表示重要地与长度减少了(并且严厉) 疾病。因为有 Hsp90 和 caveolin 的 eNOS 的 co-immunoprecipitation 同样在肝脏硬化症的老鼠减少了， eNOS 活动没被这机制修改。相反，肝硬化减少了 calmodulin 绑定到有在 eNOS 的伴随物减少的 eNOS 活动。结论：在胆汁性肝硬变，胰腺的损害是次要的但是胰腺的氮的氧化物(没有) 生产被二机制显著地减少：酶和到 eNOS 的 calmodulin 的减少的绑定的减少的表情。