CATECHOLS AND ADENOSINE IN MYOCARDIAL PRECONDITIONING

儿茶酚和腺苷在心肌预处理中的作用

• 批准号: 2771358
• 负责人: MICHAEL Victor COHEN
• 金额: $ 19.19万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2771358
• 关键词: adenosine; catecholamines; chemoprevention; dogs; enzyme activity; heart cell; heart disorder; heart pharmacology; laboratory rabbit; microdialysis; myocardial ischemia /hypoxia; phosphatase inhibitor; phosphorylation; polymerization; protective chemical group; protein kinase C; protein tyrosine kinase; protein tyrosine phosphatase; species difference; staurosporine; stress proteins

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.

描述（改编自申请人的摘要）：本提案将 测试关于提供保护机制的几个新假设 通过预处理。 由于PKC的核心重要性， 预处理的保护作用及其争议 在较大的物种如狗和猪中，PKC激活的需要 在分离的犬心肌细胞中的预处理中， 评估技术因素或真正的物种差异是否 迄今为止，在狗中阻止了PKC假说的证实。 最近 数据显示酪氨酸激酶激活也参与了 保护，并且是PKC的下游，从而形成激酶级联。 研究人员将测试几种酪氨酸的参与， 激酶级联反应，尤其是p38 MAPK通路，在缺血和 药物预处理 他们将进一步检验以下假设： 这种保护途径终止于蛋白磷酸酶的抑制 由于组成型磷酸化蛋白质的最终保存， 可能是细胞骨架成分。