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  • 标题:Sustained in vivo cardiac protection by a rationally designed peptide that causes ɛ protein kinase C translocation
  • 本地全文:下载
  • 作者:Gerald W. Dorn ; Miriam C. Souroujon ; Tamar Liron
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1999
  • 卷号:96
  • 期号:22
  • 页码:12798-12803
  • DOI:10.1073/pnas.96.22.12798
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Brief periods of cardiac ischemia trigger protection from subsequent prolonged ischemia (preconditioning). {varepsilon} Protein kinase C ({varepsilon}PKC) has been suggested to mediate preconditioning. Here, we describe an {varepsilon}PKC-selective agonist octapeptide, {psi}{varepsilon} receptor for activated C-kinase ({psi}{varepsilon}RACK), derived from an {varepsilon}PKC sequence homologous to its anchoring protein, {varepsilon}RACK. Introduction of {psi}{varepsilon}RACK into isolated cardiomyocytes, or its postnatal expression as a transgene in mouse hearts, increased {varepsilon}PKC translocation and caused cardio-protection from ischemia without any deleterious effects. Our data demonstrate that {varepsilon}PKC activation is required for protection from ischemic insult and suggest that small molecules that mimic this {varepsilon}PKC agonist octapeptide provide a powerful therapeutic approach to protect hearts at risk for ischemia.
  • 关键词:preconditioning ; hypoxia ; transgenic pseudoreceptors for activated C-kinase ; ischemia
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