OXYRADICALS, ADENOSINE, STRESS PROTEINS AND PRECONDITION

描述：（改编自摘要）：最近的研究表明， 短暂暴露于局部缺血使心脏能够更好地耐受 随后更长时间的缺血性损伤，这种现象称为缺血性损伤， 预处理这个提议的第一个假设是， 预处理伴随着增强和持续的基因表达 大鼠和兔子心脏中的热休克蛋白。除了HSP 70， 申请人将探索其它应激蛋白如HSP 27的作用， 60和90。第二个假设是槲皮素，一种抑制剂， 热休克转录因子，通过阻断预处理， 热休克蛋白的合成。第三个假设是氧自由基 直接触发预处理和清除自由基， 抗氧化剂减弱来自预处理的保护， 减少HSPs的表达。第四个假设是， 在预处理过程中腺苷A1受体的激活导致 HSPs的表达增强。申请人将审查 腺苷激动剂和拮抗剂对预适应和HSP合成的影响 在老鼠和兔子身上。第五个假设是， 热休克蛋白介导的第二个保护窗口，发展24小时 缺血预处理后。申请人期望回答 以下问题：（1）预处理是否诱导表达 HSP 27、60、90与HSP 70的关系;（2）HSP 70与HSP 27、60、90的关系 预适应早期或晚期的氧自由基是否触发 诱导HSP预处理;（4）腺苷受体是否 活化诱导HSP的表达，导致预处理。

DESCRIPTION: (Adapted from abstract): Recent studies have shown that a brief exposure to ischemia renders the heart better able to tolerate a subsequent longer ischemic insult, a phenomenon called ischemic preconditioning. The first hypothesis of this proposal is that ischemic preconditioning is accompanied by enhanced and sustained gene expression of HSPs in the heart of rats and rabbits. In addition to HSP70, the applicants will explore the role of other stress proteins such as HSP27, 60, and 90. The second hypothesis is that quercitine, an inhibitor of the heat shock transcription factor, blocks preconditioning by blocking the synthesis of HSPs. The third hypothesis is that oxygen radicals directly trigger the preconditioning and that scavenging of radicals by antioxidants attenuates the protection derived from preconditioning and reduces the expression of HSPs. The fourth hypothesis is that activation of adenosine A1-receptors during preconditioning results in enhanced expression of HSPs. The applicants will examine the effects of adenosine agonists and antagonists on preconditioning and HSP synthesis in rats as well as rabbits. The fifth hypothesis is that synthesis of HSPs mediates the second window of protection which develops 24 hours after ischemic preconditioning. The applicants anticipate answering the following questions: (1) whether preconditioning induces the expression of HSP27, 60, and 90 in addition to HSP70; (2) whether HSPs are involved in preconditioning early or late; (3) whether oxygen radicals trigger the preconditioning by inducing HSP; and (4) whether adenosine receptor activation induces expression of HSPs resulting in preconditioning.