CATECHOLS AND ADENOSINE IN MYOCARDIAL PRECONDITIONING

描述(改编自申请人的摘要)：本提案将 检验关于所提供的保护机制的几个新假设 通过预适应。由于提议的PKC的核心重要性 预适应的保护及其参与的争议 在较大的物种中，如狗和猪，PKC激活的要求 在对分离的犬心肌细胞进行预适应时，将确定 评估技术因素或真正的物种差异是否具有 到目前为止，还没有在狗身上证实PKC假说。近期 数据显示，酪氨酸激酶的激活也参与了 保护，这是下游的蛋白激酶C，从而形成一个激酶级联。 调查人员将测试几种酪氨酸的参与程度 在脑缺血和再灌注损伤中，激酶级联反应，尤其是p38 MAPK通路。 药物预适应。他们将进一步检验这一假设 这种保护途径终止于对蛋白磷酸酶的抑制。 随着构成磷酸化蛋白质的最终保存， 可能是细胞骨架元素。

DESCRIPTION (adapted from the applicant's abstract): This proposal will test several new hypotheses concerning the mechanism of protection provided by preconditioning. Because of the proposed central importance of PKC to preconditioning's protection and the controversy surrounding its involvement in larger species such as the dog and pig, the requirement of PKC activation in preconditioning in isolated canine cardiomyocytes will be determined to evaluate whether technical factors or true species differences have heretofore prevented confirmation of the PKC hypothesis in dogs. Recent data reveal that tyrosine kinase activation is also involved in the protection, and that is downstream of PKC, thus forming a kinase cascade. The investigators will test the involvement of several of the tyrosine kinase cascades, especially the p38 MAPK pathway, in ischemic and pharmacologic preconditioning. They will further test the hypothesis that this pathway to protection terminates in inhibition of a protein phosphatase with ultimate preservation of constitutively phosphorylated proteins, possibly cytoskeletal elements.