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

缺血预处理（IPC）和高温（HT）是已知的提供心肌保护， 例如心肌梗塞。而HT诱导热休克蛋白（HSP），它可以作为 在预防心肌梗死中，IPC已知诱导一氧化氮（NO），其可 介导心脏中的各种过程以最小化缺血性损伤。我们的初步研究与孤立 心肌细胞已经表明，通过热应激诱导的HSP 90可以激活NOS酶。 因此，我们推测HT诱导的HSP90可以激活NOS酶 在热应激的心脏中，HT和IPC以共同的途径起作用，以最大限度地减少缺血性损伤： 也就是说，在这两种情况下，NOS酶被激活以产生高丰度的NO。 氧对线粒体中的细胞色素c氧化酶位点具有高且相等的亲和力， 在IPC和热应激心脏中，预期心肌细胞的消耗和呼吸减少。 然而，诱导型NO在IPC和热应激心脏耗氧中的作用尚不清楚， 以前被研究过。因此，本提案的主要目标是研究NO调节的氧 消耗PC和热应激的心脏。我们建议使用电子顺磁共振 (EPR)采用高灵敏度的LiPc微晶作为探针和专门设计的EPR仪器进行血氧测定， 直接测量正常心脏、IPC心脏和热应激心脏的耗氧量。本 该提案有三个主要目标：（1）氧消耗和功能恢复的直接相关性， （2）研究缺血预处理过程中产生的NO对心肌缺血再灌注损伤的影响。 研究热应激诱导的热休克蛋白对心肌氧耗的影响，探讨热应激对心肌氧耗的影响。 心肌耗氧量使用其他支持性研究，可以证明在这两种情况下（IPC）， 和HT），NO介导的呼吸调节是心肌保护的关键机制之一。总体而言， 本项目将确定NO与心脏耗氧量之间的关系 受PC和HT，并提供深入了解心脏保护的实际机制。

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.