首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion.
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Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion.

机译:钙调蛋白依赖性环核苷酸磷酸二酯酶在心脏缺血再灌注的实验大鼠模型中。

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摘要

In the present study, we investigated the activity and expression of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) and the effects of calpains in rat heart after ischemia and reperfusion. Immunohistochemical studies indicated that CaMPDE in normal heart is localized in myocardial cells. Rat ischemic heart showed a decrease in CaMPDE activity in the presence of Ca2+ and calmodulin; however, in ischemic-reperfusion tissue a progressive increase in Ca2+ and calmodulin-independent cyclic nucleotide phosphodiesterase (CaM-independent PDE) activity was observed. Perfusion of hearts with cell-permeable calpain inhibitor suppressed the increase of Ca2+ and CaM-independent PDE activity. Protein expression of CaMPDE was uneffected by hypoxic injury to rat myocardium. The purified heart CaMPDE was proteolyzed by calpains into a 45 kDa immunoreactive fragment in vitro. Based on these results, we propose that hypoxic injury to rat myocardium results in the generation of CaM-independent PDE by calpain mediated proteolysis, allowing the maintenance of cAMP concentrations within the physiological range.
机译:在本研究中,我们研究了钙调蛋白依赖性环核苷酸磷酸二酯酶(CaMPDE)的活性和表达以及钙蛋白酶在缺血和再灌注后对大鼠心脏的影响。免疫组织化学研究表明,正常心脏中的CaMPDE位于心肌细胞中。在Ca2 +和钙调蛋白的存在下,大鼠缺血心脏的CaMPDE活性降低。但是,在缺血性再灌注组织中,观察到Ca2 +和钙调蛋白非依赖性环状核苷酸磷酸二酯酶(CaM非依赖性PDE)活性逐渐增加。用可渗透细胞的钙蛋白酶抑制剂灌注心脏可抑制Ca2 +和CaM依赖性PDE活性的增加。缺氧损伤大鼠心肌不会影响CaMPDE的蛋白表达。钙蛋白酶将纯化的心脏CaMPDE体外水解成45 kDa免疫反应片段。基于这些结果,我们认为对大鼠心肌的低氧损伤会导致钙蛋白酶介导的蛋白水解作用产生非CaM依赖性PDE,从而使cAMP的浓度维持在生理范围内。

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