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  • Title: Increased protein kinase C and isozyme redistribution in pressure-overload cardiac hypertrophy in the rat.
    Author: Gu X, Bishop SP.
    Journal: Circ Res; 1994 Nov; 75(5):926-31. PubMed ID: 7923639.
    Abstract:
    Protein kinase C (PKC) activity and isozyme distribution were evaluated during development of pressure-overload-induced cardiac hypertrophy. Three-week-old rats were loosely banded on the ascending aorta (left ventricular hypertrophy [LVH] group). Two weeks later, when left ventricular mass was 50% greater than in the sham-operated control group and cardiac mass was still rapidly increasing beyond that of normal growth, PKC activity and [3H]phorbol 12,13-dibutyrate (PDBu) binding capacity were determined. In LVH, PKC activity was 119 +/- 14%, 158 +/- 17%, and 152 +/- 9% of the control value in cytosol, membrane, and nuclear-cytoskeletal fractions, respectively (n = 9 or 10). [3H]PDBu binding assay revealed increased PKC concentration in LVH cytosolic (control, 0.51 +/- 0.06 pmol/L per milligram; LVH, 0.78 +/- 0.09 pmol/L per milligram; n = 5; P < .05) and membrane fractions (control, 1.33 +/- 0.15; LVH, 2.32 +/- 0.39; n = 5; P < .05). Scatchard analysis indicated no difference in Kd values between control and LVH groups. Immunoblot analysis using PKC isoform-specific antibodies showed that both Ca(2+)-dependent (alpha and beta) and Ca(2+)-independent (delta, epsilon, and zeta) isoforms were present in the left ventricle. Compared with the control value, there was increased concentration in the membrane and nuclear-cytoskeletal fractions for beta 1,2 and epsilon and in the cytosol for beta 1,2. PKC-delta could be detected only in the nuclear-cytoskeletal fraction and was not changed in LVH. PKC-alpha and -zeta were present in all three fractions but were not altered in LVH. These data indicate that PKC activity and concentration increase during development of LVH induced by pressure overload. The increased PKC isozymes were mainly limited to PKC-beta 1,2 and PKC-epsilon, and the increase was present mainly in the membrane and nuclear-cytoskeletal fractions.
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