OXYRADICALS, ADENOSINE, STRESS PROTEINS AND PRECONDITION

描述：(摘自摘要)：最近的研究表明， 短暂的缺血使心脏能够更好地耐受 随后更长时间的缺血性侮辱，一种称为缺血性的现象 预适应。这一提议的第一个假设是缺血 预适应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HSP70， 申请者将探索其他应激蛋白的作用，如HSP27， 60和90。第二种假设是，槲皮碱是一种抗癌药物。 热休克转录因子通过阻断来阻断预适应 热休克蛋白的合成。第三个假设是氧自由基 直接触发预适应和清除自由基，通过 抗氧化剂减弱了由预适应和 减少热休克蛋白的表达。第四个假设是 在预适应过程中腺苷A1受体的激活导致 热休克蛋白的表达增强。申请者将检查以下方面的影响 腺苷激动剂和拮抗剂对预适应和热休克蛋白合成的影响 无论在老鼠身上还是在兔子身上。第五个假设是 热休克蛋白调节24小时内形成的第二个保护窗口 缺血预适应后。应聘者期待着回答 以下问题：(1)预适应是否诱导表达 除HSP70外，还包括HSP27、60和90；(2)是否涉及HSPs 早期或晚期的预适应；(3)氧自由基是否触发 诱导热休克蛋白的预适应；(4)腺苷受体是否 激活诱导热休克蛋白的表达，导致预适应。

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.