Abstract

We examined the possible involvement of nuclear proteins in the pathogenesis of a naturally occurring model of congestive cardiomyopathy(CCM) in turkeys. The protein composition of myocardial nuclei was compared in CCM (n=18) and control (n=9) turkeys, 70-140 days old. CCM hearts as a group had a higher histone content (1.75±0.09(SD) mg/g vs 1.65±0.07 in Con, P<0.01) and histone/non-histone protein ratio (1.07±0.07 vs 0.95±0.02, P<0.01). The latter was independent of age and correlated well (r=0.89) with the degree of cardiac dilation. The electrophoretic pattern of chromatin proteins did not differ in the two experimental groups. In vitro phosphorylation of nuclei was decreased in CCM hearts (9.7± 0.2 vs 12.8±0.1 pmole32/mg prot/15 min, P<0.01). The decrease was due to lower NHP phosphorylation (5.78±1.38 vs 8.33±0.81 pmole 32P/mg prot/15 min, P<0.01). DEAE-Sephacel chromatography separated cyclic AMP-dependent and independent nuclear protein kinases. Lower cAMP-independent activities were present in CCM hearts. There was a significant linear correlation between NHP phosphorylation and degree of cardiac dilation (r=0.75) or contractility as reflected by left ventricular systolic time intervals (r=0.79). SDS-polyacrylamide gel electrophoresis of phosphorylated nucleoproteins revealed differences in the lower molecular weight species of NHPs between control and CCM hearts. These results suggest that development of this cardiomyopathy is associated with, and may be secondary to, changes in the composition and function of myocardial nucleoproteins.

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