Heat Shock Proteins, Nitric Oxide and Oxygen Consumption in the Heart

众所周知，缺血预适应(IPC)和高温(HT)可提供心肌保护。 心肌梗死等损伤。而高温则诱导热休克蛋白(HSP)，热休克蛋白可作为 在预防心肌梗死中，IPC可诱导一氧化氮(NO)，这可以 调节心脏中的各种过程，将缺血损伤降至最低。我们对孤立的初步研究 心肌细胞研究表明，热应激诱导的HSP90可以激活NOS酶。 因此，我们在目前的方案中假设，HT诱导的HSP90可以激活NOS酶 在热应激心脏中，HT和IPC以共同的途径工作，将缺血损伤降至最低： 也就是说，在这两种情况下，NOS酶都被激活以产生高丰度的NO。既然不是和 与线粒体中的细胞色素c氧化物酶有很高的亲和力。 心肌细胞的消耗和呼吸，预计在IPC和热应激心脏中会减少。 然而，诱导NO在IPC和热应激心脏耗氧量中的作用尚未见报道 已经被研究过了。因此，这项建议的主要目标是研究NO调节的氧 PC消费受累，心脏热应激。我们建议使用电子顺磁共振 以高灵敏度的LiPc微晶为探针的EPR血氧仪和专门设计的EPR仪器， 目的：直接测量正常、缺血预适应和热应激心脏的耗氧量。现在 建议有三个主要目标：(1)氧耗量与功能恢复的直接相关性 (2)研究缺血预适应过程中产生的NO对心肌缺血损伤的影响。 (3)研究热应激诱导的热休克蛋白在心肌氧耗中的作用。 心肌耗氧量。使用其他支持性研究，将证明在这两种情况下(IPC NO介导的呼吸调节是心脏保护的关键机制之一。总的来说， 该项目将确定一氧化氮与心脏耗氧量之间的关系 并提供对心脏保护的实际机制的洞察。

Ischemic preconditioning (IPC) and hyperthermia (HT) are known to offer cardioprotection from ischemic injury such as myocardial infarction. While HT induces the heat shock proteins (HSP), which can act as chaperones in preventing myocardial infarction, IPC is known to induce nitric oxide (NO), which can mediate various processes in the heart to minimize ischemic injury. Our preliminary studies with isolated cardiomyocytes have indicated that the HSP90, induced through heat stress, can activate the NOS enzymes. Therefore we hypothesized in the present proposal that HSP90 induced by HT can activate the NOS enzymes in the heat stressed hearts and thus HT and IPC work in a common pathway to minimize the ischemic injury: i.e., in both cases the NOS enzymes are activated to produce high abundance of NO. Since the NO and oxygen have high and equal affinity to the cytochrome c oxidase site in the mitochondria, oxygen consumption and respiration of cardiomyocytes, is expected to be reduced in IPC and heat stressed hearts. However, the role of induced NO in the oxygen consumption in IPC subjected and heat stressed hearts has not been studied before. Thus the main goal of this proposal is to investigate the NO regulated oxygen consumption in PC subjected and heat stressed hearts. We propose to use electron paramagnetic resonance (EPR) oximetry with high sensitive LiPc microcrystals as probe and specially designed EPR instrumentation, to directly measure oxygen consumption in normal, IPC subjected and heat stressed hearts. The present proposal has three main aims: (1) Direct correlation of oxygen consumption and functional recovery in ischemically injured hearts; (2) To study the effect of NO generated during ischemic preconditioning on the myocardial oxygen consumption; (3) To study the role of heat shock proteins, induced by heat stress, on the myocardial oxygen consumption. Using other supporting studies, it would be proved that in both cases (IPC and HT) the NO mediated regulation of respiration is one of the key mechanisms of cardioprotection. Overall, this project will determine the relationship between the NO and the oxygen consumption in the hearts subjected to PC and HT and provide insight into the actual mechanism of cardioprotection.