文章基本信息

标题：B-Type Natriuretic Peptide-Induced Cardioprotection against Reperfusion Is Associated with Attenuation of Mitochondrial Permeability Transition
本地全文：下载
作者：Yiguo Sun ; Yun Zhang ; Ming Yan 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：9
页码：1545-1551
DOI：10.1248/bpb.32.1545
出版社：The Pharmaceutical Society of Japan
摘要：B-type natriuretic peptide (BNP) is one peptide hormone released in response to myocyte stretch, whose functions play significant roles in health and disease. Its physiologic effects result in improved loading conditions and have led to the development of recombinant BNP as a therapeutic agent for heart failure. Previous work has identified that BNP protect myocardium against reperfusion injury through mitochondrial pathway. Mitochondria are both essential effectors of cardioprotection and primary targets of cardioprotective signaling. Their role during reperfusion is particularly critical because of the conditions that promote both apoptosis by the mitochondrial pathway and necrosis by irreversible damage to mitochondria in association with mitochondrial permeability transition pores (mPTP). After an episode of myocardial ischemia, opening of mPTP, at the onset of reperfusion, is a critical determinant of myocyte death. The relationship of BNP and mPTP in mediating reperfusion-induced cardiomyocytes injury is a novel investigative area. In this study, our results indicated that the beneficial effect of BNP in cultured cardiomyocytes subjected to reperfusion is associated with attenuation of mPTP opening, resultant mitochondrial dysfunction and apoptosis. Further investigation of underlying mechanisms revealed that these were associated with BNP-mediated repolarization of mitochondrial membrane potential (Δψ_m), inhibition of reactive oxygen species (ROS) generation, improvement of Bcl-2 level, and inhibition of Bax and second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein-binding protein with a low isoelectric point (Smac/DIABLO) levels. In summary, we demonstrate that BNP exerts protective actions within reperfusion by inhibiting mPTP opening and these roles of BNP may involve phosphatidylinositol 3-kinase (PI3K) dependent pathway.
关键词：B-type natriuretic peptide;mitochondrial permeability transition;cardiomyocyte;reperfusion