Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation

Gerald W. Dorn, Miriam C. Souroujon, Tamar Liron, Che Hong Chen, Mary O. Gray, Hui Zhong Zhou, Michael Csukai, Guangyu Wu, John N. Lorenz, Daria Mochly-Rosen

Research output: Contribution to journalArticle

316 Citations (Scopus)

Abstract

Brief periods of cardiac ischemia trigger protection from subsequent prolonged ischemia (preconditioning). ε Protein kinase C (εPKC) has been suggested to mediate preconditioning. Here, we describe an εPKC-selective agonist octapeptide, ψε receptor for activated C-kinase (ψ®ACK), derived from an εPKC sequence homologous to its anchoring protein, εRACK. Introduction of ψεRACK into isolated cardiomyocytes, or its postnatal expression as a transgene in mouse hearts, increased εPKC translocation and caused cardio-protection from ischemia without any deleterious effects. Our data demonstrate that εPKC activation is required for protection from ischemic insult and suggest that small molecules that mimic this εPKC agonist octapeptide provide a powerful therapeutic approach to protect hearts at risk for ischemia.

Original languageEnglish (US)
Pages (from-to)12798-12803
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number22
DOIs
StatePublished - Oct 26 1999

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Protein Kinase C
Peptides
Ischemia
Sequence Homology
Transgenes
Cardiac Myocytes
Proteins

Keywords

  • Hypoxia
  • Ischemia
  • Preconditioning
  • Transgenic pseudoreceptors for activated C- kinase

ASJC Scopus subject areas

  • General

Cite this

Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation. / Dorn, Gerald W.; Souroujon, Miriam C.; Liron, Tamar; Chen, Che Hong; Gray, Mary O.; Zhou, Hui Zhong; Csukai, Michael; Wu, Guangyu; Lorenz, John N.; Mochly-Rosen, Daria.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 22, 26.10.1999, p. 12798-12803.

Research output: Contribution to journalArticle

Dorn, Gerald W. ; Souroujon, Miriam C. ; Liron, Tamar ; Chen, Che Hong ; Gray, Mary O. ; Zhou, Hui Zhong ; Csukai, Michael ; Wu, Guangyu ; Lorenz, John N. ; Mochly-Rosen, Daria. / Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 22. pp. 12798-12803.
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