Nulceoprotein changes in the hearts of cardiomyopathic turkeys.

Abstract

The possible involvement of nuclear proteins in the pathogenesis of a spontaneously occurring model of congestive cardiomyopathy in turkeys was examined. This model is characterised by cardiac hypertrophy and dilatation, reduced cardiac output and depressed contractility. The protein composition of myocardial nuclei was compared in normal (n = 9) and cardiomyopathic (n = 18) turkeys, 70 to 140 days old. Myopathic hearts as a group have a higher histone content (1.75 +/- 0.09 (SD) mg . mg DNA-1 vs 1.65 +/- 0.07 in controls, P less than 0.01) and histone/nonhistone protein (NHP) ratio (1.07 +/- 0.07 vs 0.95 +/- 0.02 in controls, P less than 0.01). The latter was independent of age and correlated well with the degree of cardiac dilatation. The electrophoretic patterns of chromatin proteins was decreased in myopathic hearts. This decrease was primarily accounted for by lower NHP phosphorylation (5.78 +/- 1.38 pmol 32P . mg prot-1 . 15 min-1 vs 8.33 +/- 0.81 in controls, P less than 0.01). DEAE-Sephacel chromatography separated cyclic AMP-dependent and -independent nuclear protein kinases with similar substrate specificities but lower specific activities in myopathic hearts. SDS-polyacrylamide similar substrate specificities but lower specific activities in myopathic hearts. SDS-polyacrylamide gel electrophoresis of phosphorylated nucleoproteins revealed differences in the lower molecular species of NHPs between control and myopathic hearts. There was a significant correlation between NHP phosphorylation and degree of cardiac dilatation (r = -0.78) or contractility as reflected by left ventricular systolic time intervals (r = -0.57). These results suggest that development of this model of spontaneous cardiomyopathy is associated with, and may, in part, be secondary to changes in the composition and function of myocardial nucleoproteins.