MITOCHONDRIAL STRESS PROTEINS AND CARDIOPROTECTION

描述(申请人的逐字描述)：虽然，已经有 心肌缺血、心肌梗死的治疗进展 仍然是美国主要的死亡原因。急性心肌梗死是 通常由供血的冠状动脉血栓形成或闭塞引起 心脏的左心室。没有血液流向心脏 肌肉会导致严重的细胞损伤，最终会损害 肌肉的收缩能力。这其中要归功于 限制氧输送，减少线粒体氧化 磷酸化，并有助于降低细胞内的ATP水平。 研究表明，线粒体的自我修复能力 血流恢复后可能是导致 心肌细胞死亡。最近的研究表明，这种心肌细胞的一部分 死亡是通过细胞凋亡实现的。生物体内的主要蛋白质组装结构之一 线粒体由分子伴侣或线粒体应激组成 蛋白质。这些蛋白质被称为线粒体HSP70、HSP60和HSP10。 这最后两种蛋白质形成了伴侣蛋白复合体，它与ATP一起是 参与大多数线粒体蛋白的组装 包括参与氧化磷酸化的酶复合体。我们有 发现心肌细胞中HSP60和HSP10的表达增加 使心肌细胞对缺血损伤有显著的耐受性，有趣的是，我们 发现线粒体过度表达的这种保护作用的一部分 应激蛋白是由于诱导的细胞凋亡率减少所致 热休克蛋白60和热休克蛋白10对脑缺血再灌注损伤的保护作用 似乎是通过它们与细胞色素c的结合和对这一点的保留来调节的 线粒体中的最后一种蛋白质，因此可能会降低 因此，我们认为细胞凋亡的主要罪魁祸首--半胱氨酸酶的激活 更好地理解线粒体热休克蛋白是如何 在缺血/再灌注损伤中保护心肌细胞将允许我们 利用这种内生防御机制

DESCRIPTION (the applicant's description verbatim): Although, there has been much progress in the management of myocardial ischemia, myocardial infarction remains the major cause of death in the U.S. Acute myocardial infarction is commonly caused by thrombosis or occlusion of the coronary arteries which feed the left ventricle of the heart. The absence of blood flow to the cardiac muscle results in severe cellular damage that eventually compromises the muscle's ability to contract. This is due, among other things, to the limitation in oxygen delivery that reduces mitochondrial oxidative phosphorylation and contributes to the reduction of intracellular ATP levels. Research has shown that the inability of the mitochondria to self-repair following restoration of blood flow may be a crucial event leading to myocardial cell death. Recent studies show that part of this myocardial cell death is through apoptosis. One of the main protein assembly structures in the mitochondria is made up by the molecular chaperones or mitochondrial stress proteins. These proteins are known as the mitochondrial hsp70, hsp60 and hsp10. These last two proteins form the chaperonin complex which together with ATP is involved in the assembly of the majority of the mitochondrial proteins including the enzyme complexes involved in oxidative phosphorylation. We have found that increased expression of the hsp60 and hsp10 in cardiomyocytes renders the myocyte significantly tolerant to ischemic injury Interestingly, we find that part of this protection effect of overexpressing the mitochondrial stress proteins is due to a reduction in the amount of apoptosis induced by ischemia/reperfusion We find that the protective effect by hsp60 and hsp10 seems to be mediated by their binding to cytochrome c and the retention of this last protein inside the mitochondria and therefore potentially decreasing the activation of the caspases, the main culprits of apoptosis We therefore believe that a better understanding of the mechanism of how the mitochondrial hsps protect the cardiomyocyte during ischemia/reperfusion injury will permit us to harness this endogenous defense mechanism