Abstract
Calcineurin, a calcium-regulated serine/threonine phosphatase, has been reported to be one of the signaling molecules in cardiac hypertrophy, yet it is currently under investigation whether its pathway is implicated in the phenotypic regulation of cardiac muscle. To elucidate this question, we compared the expression pattern of myosin heavy chain (MHC) isoforms (alpha- and beta-MHCs) in right (RV) and left (LV) ventricules obtained from control and cyclosporin A (CsA, a calcineurin inhibitor)-treated rats. Rats, aged 8 weeks, were injected i.p. with normal saline (control group) or 10 mg/kg CsA (CsA-treated group) daily for 2 weeks. Alpha- and beta-MHCs were separated with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and their relative proportions were densitometrically quantified. The relative proportions of alpha- and beta-MHCs (mean±SD, n=4) were 70.7±3.6％ and 29.3±3.6％ in RV, 72.0±3.9％ and 28.0±3.9％ in LV of control group and 80.0±1.4％ and 20.0±1.4％ in RV, 79.5±2.4％ and 20.5±2.4％ in LV of CsA-treated group, indicating a significant (p<0.05) increase in the relative proportion of alpha-MHC at the expense of that of beta-MHC in both right and left ventricules in association with the CsA treatment. These results suggest that calcineurin pathway is implicated in a conversion of cardiac muscle towards more beta-MHC-rich phenotype. [Jpn J Physiol 54 Suppl:S121 (2004)]
