Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and εPKC

Leon Chen, Harvey Hahn, Guangyu Wu, Che Hong Chen, Tamar Liron, Deborah Schechtman, Gabriele Cavallaro, Lucia Banci, Yiru Guo, Roberto Bolli, Gerald W. Dorn, Daria Mochly-Rosen

Research output: Contribution to journalArticle

Abstract

Conflicting roles for protein kinase C (PKC) isozymes in cardiac disease have been reported. Here, δPKC-selective activator and inhibitor peptides were designed rationally, based on molecular modeling and structural homology analyses. Together with previously identified activator and inhibitor peptides of εPKC, δPKC peptides were used to identify cardiac functions of these isozymes. In isolated cardiomyocytes, perfused hearts, and transgenic mice, δPKC and εPKC had opposing actions on protection from ischemia-induced damage. Specifically, activation of εPKC caused cardioprotection whereas activation of δPKC increased damage induced by ischemia in vitro and in vivo. In contrast, δPKC and εPKC caused identical nonpathological cardiac hypertrophy; activation of either isozyme caused nonpathological hypertrophy of the heart. These results demonstrate that two related PKC isozymes have both parallel and opposing effects in the heart, indicating the danger in the use of therapeutics with nonselective isozyme inhibitors and activators. Moreover, reduction in cardiac damage caused by ischemia by perfusion of selective regulator peptides of PKC through the coronary arteries constitutes a major step toward developing a therapeutic agent for acute cardiac ischemia.

Original languageEnglish (US)
Pages (from-to)11114-11119
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number20
DOIs
StatePublished - Sep 25 2001
Externally publishedYes

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Protein Kinase C
Isoenzymes
Ischemia
Cardiomegaly
Peptides
protein kinase C kinase
C-Peptide
Therapeutic Uses
Cardiac Myocytes
Transgenic Mice
Heart Diseases
Coronary Vessels
Perfusion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and εPKC. / Chen, Leon; Hahn, Harvey; Wu, Guangyu; Chen, Che Hong; Liron, Tamar; Schechtman, Deborah; Cavallaro, Gabriele; Banci, Lucia; Guo, Yiru; Bolli, Roberto; Dorn, Gerald W.; Mochly-Rosen, Daria.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 20, 25.09.2001, p. 11114-11119.

Research output: Contribution to journalArticle

Chen, L, Hahn, H, Wu, G, Chen, CH, Liron, T, Schechtman, D, Cavallaro, G, Banci, L, Guo, Y, Bolli, R, Dorn, GW & Mochly-Rosen, D 2001, 'Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and εPKC', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 20, pp. 11114-11119. https://doi.org/10.1073/pnas.191369098
Chen, Leon ; Hahn, Harvey ; Wu, Guangyu ; Chen, Che Hong ; Liron, Tamar ; Schechtman, Deborah ; Cavallaro, Gabriele ; Banci, Lucia ; Guo, Yiru ; Bolli, Roberto ; Dorn, Gerald W. ; Mochly-Rosen, Daria. / Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and εPKC. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 20. pp. 11114-11119.
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