ε Protein kinase C in pathological myocardial hypertrophy. Analysis by combined transgenic expression of translocation modifiers and Gα(q)

Guangyu Wu, Tsuyoshi Toyokawa, Harvey Hahn, Gerald W. Dorn

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Abstract

The ε isoform of protein kinase C (PKC) has a critical cardiotrophic function in normal postnatal developing heart as demonstrated by cardiac-specific transgenic expression of εPKC-selective translocation inhibitor (εV1) and activator (ψεRACK) peptides (Mochly-Rosen, D., Wu, G., Hahn, H., Osinska, H., Liron, T., Lorenz, J. N., Robbins, J., and Dorn, G. W., II (2000) Circ. Res. 86, 1173-1179). To define the role of εPKC signaling in pathological myocardial hypertrophy, εV1 or ψεRACK were co-expressed in mouse hearts with Gα(q), a PKC-linked hypertrophy signal transducer. Compared with Gα(q) overexpression alone, co-expression of ψεRACK with Gα(q) increased εPKC particulate partitioning by 30 ± 2%, whereas co-expression of εV1 with Gα(q) reduced particulate-associated εPKC by 22 ± 1%. Facilitation of εPKC translocation by ψεRACK in Gα(q) mice improved cardiac contractile function measured as left ventricular fractional shortening (30 ± 3% Gα(q) versus 43 ± 2% ψεRACK/Gα(q), p < 0.05). Conversely, inhibition of εPKC by εV1 modified the Gα(q) nonfailing hypertrophy phenotype to that of a lethal dilated cardiomyopathy. These opposing effects of εPKC translocation activation and inhibition in Gα(q) hypertrophy indicate that εPKC signaling is a compensatory event in myocardial hypertrophy, rather than a pathological event, and support the possible therapeutic efficacy of selective εPKC translocation enhancement in cardiac insufficiency.

Original languageEnglish (US)
Pages (from-to)29927-29930
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number39
DOIs
StatePublished - Sep 29 2000
Externally publishedYes

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Protein Kinase C
Hypertrophy
Dilated Cardiomyopathy
Transducers
Protein Isoforms
Chemical activation
Phenotype
Peptides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

ε Protein kinase C in pathological myocardial hypertrophy. Analysis by combined transgenic expression of translocation modifiers and Gα(q). / Wu, Guangyu; Toyokawa, Tsuyoshi; Hahn, Harvey; Dorn, Gerald W.

In: Journal of Biological Chemistry, Vol. 275, No. 39, 29.09.2000, p. 29927-29930.

Research output: Contribution to journalArticle

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