Cardiotrophic effects of protein kinase C ε

Analysis by in vivo modulation of PKCε translocation

Daria Mochly-Rosen, Guangyu Wu, Harvey Hahn, Hanna Osinska, Tamar Liron, John N. Lorenz, Atsuko Yatani, Jeffrey Robbins, Gerald W. Dorn

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Protein kinase C (PKC) is a key mediator of many diverse physiological and pathological responses. Although little is known about the specific in vivo roles of the various cardiac PKC isozymes, activation-induced translocation of PKC is believed to be the primary determinant of isozyme- specific functions. Recently, we have identified a catalytically inactive peptide translocation inhibitor (εV1) and translocation activator (ψεRACK [receptors for activated C kinase]) specifically targeting PKCε. Using cardiomyocyte-specific transgenic expression of these peptides, We combined loss- and gain-of-function approaches to elucidate the in vivo consequences of myocardial PKCε signaling. As expected for a PKCε RACK binding peptide, confocal microscopy showed that εV1 decorated cross-striated elements and intercalated disks of cardiac myocytes. Inhibition of cardiomyocyte PKCε by εV1 at lower expression levels upregulated α-skeletal actin gene expression, increased cardiomyocyte cell size, and modestly impaired left ventricular fractional shortening. At high expression levels, εV1 caused a lethal dilated cardiomyopathy. In contrast, enhancement of PKCε translocation with ψεRACK resulted in selectively increased β myosin heavy chain gene expression and normally functioning concentric ventricular remodeling with decreased cardiomyocyte size. These results identify for the first time a role for PKCε signaling in normal postnatal maturational myocardial development and suggest the potential for PKCε activators to stimulate 'physiological' cardiomyocyte growth.

Original languageEnglish (US)
Pages (from-to)1173-1179
Number of pages7
JournalCirculation Research
Volume86
Issue number11
DOIs
StatePublished - Jun 9 2000
Externally publishedYes

Fingerprint

Protein Kinase C
Cardiac Myocytes
Peptides
Isoenzymes
Nijmegen Breakage Syndrome
Gene Expression
Ventricular Remodeling
Myosin Heavy Chains
Dilated Cardiomyopathy
Cell Size
Confocal Microscopy
Actins
Growth

Keywords

  • Cardiac hypertrophy
  • Cardiomyopathy
  • Protein kinase C
  • Transgenic mouse

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Mochly-Rosen, D., Wu, G., Hahn, H., Osinska, H., Liron, T., Lorenz, J. N., ... Dorn, G. W. (2000). Cardiotrophic effects of protein kinase C ε: Analysis by in vivo modulation of PKCε translocation. Circulation Research, 86(11), 1173-1179. https://doi.org/10.1161/01.RES.86.11.1173

Cardiotrophic effects of protein kinase C ε : Analysis by in vivo modulation of PKCε translocation. / Mochly-Rosen, Daria; Wu, Guangyu; Hahn, Harvey; Osinska, Hanna; Liron, Tamar; Lorenz, John N.; Yatani, Atsuko; Robbins, Jeffrey; Dorn, Gerald W.

In: Circulation Research, Vol. 86, No. 11, 09.06.2000, p. 1173-1179.

Research output: Contribution to journalArticle

Mochly-Rosen, D, Wu, G, Hahn, H, Osinska, H, Liron, T, Lorenz, JN, Yatani, A, Robbins, J & Dorn, GW 2000, 'Cardiotrophic effects of protein kinase C ε: Analysis by in vivo modulation of PKCε translocation', Circulation Research, vol. 86, no. 11, pp. 1173-1179. https://doi.org/10.1161/01.RES.86.11.1173
Mochly-Rosen, Daria ; Wu, Guangyu ; Hahn, Harvey ; Osinska, Hanna ; Liron, Tamar ; Lorenz, John N. ; Yatani, Atsuko ; Robbins, Jeffrey ; Dorn, Gerald W. / Cardiotrophic effects of protein kinase C ε : Analysis by in vivo modulation of PKCε translocation. In: Circulation Research. 2000 ; Vol. 86, No. 11. pp. 1173-1179.
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