Gy. Wu et al., epsilon Protein kinase C in pathological myocardial hypertrophy - Analysisby combined transgenic expression of translocation modifiers and G alpha(q), J BIOL CHEM, 275(39), 2000, pp. 29927-29930
The epsilon isoform of protein kinase C (PKC) has a critical cardiotrophic
function in normal postnatal developing heart as demonstrated by cardiac-sp
ecific transgenic expression of epsilon PKC-selective translocation inhibit
or (epsilon V1) and activator (psi epsilon RACK) 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 ep
silon PKC signaling in pathological myocardial hypertrophy, epsilon V1 or p
si epsilon RACK were coexpressed in mouse hearts with G alpha(q), a PKC-lin
ked hypertrophy signal transducer. Compared with G alpha(q) overexpression
alone, co-expression of psi epsilon RACK with G alpha(q) increased epsilon
PKC particulate partitioning by 30 +/- 2%, whereas co-expression of epsilon
V1 with G alpha(q) reduced particulate-associated epsilon PKC by 22 +/- 1%
. Facilitation of epsilon PKC translocation by psi epsilon RACK in G alpha(
q) mice improved cardiac contractile function measured as left ventricular
fractional shortening (30 +/- 3% G alpha(q) versus 43 +/- 2% psi epsilon RA
CK/ G alpha(q), p < 0.05). Conversely, inhibition of epsilon PKC by epsilon
V1 modified the G alpha(q) nonfailing hypertrophy phenotype to that of a l
ethal dilated cardiomyopathy. These opposing effects of epsilon PKC translo
cation activation and inhibition in G alpha(q) -hypertrophy indicate that e
psilon PKC signaling is a compensatory event in myocardial hypertrophy, rat
her than a pathological event, and support the possible therapeutic efficac
y of selective epsilon PKC translocation enhancement in cardiac insufficien
cy.