Myocardial chromatin activation in experimental hyperthyroidism in rats. Role of nuclear non-histone proteins.

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Abstract
Experimental hyperthyroidism induced in rats by daily injections of 20 .mu.g of 3'',3'',5''-triiodothyronine (T3) resulted in a prompt increase in cardiac weight and RNA content. The mechanism of the RNA synthesis stimulation was studied by comparing template activity of myocardial chromatin from rats treated with T3 for 7 days with chromatin from euthyroid controls. Hyperthyroidism resulted in significant enhancement of chromatin template activity (184 .+-. 7.1 pmol 3H-UMP/mg per min vs. 106 .+-. 4.8 pmol 3H-UMP/mg per min, P < 0.001) and a significantly higher (102% more) number of transcription initiation sites. Dissociation of chromatin and subsequent reconstitution with nucleoproteins from both hyper- and euthyroid rats demonstrated that the non-histone nuclear fraction (NHP) accounted for the differences in RNA synthesis between the 2 groups. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoretic patterns of NHPs were similar for the 2nd groups, but NHPs from hyperthyroid rats exhibited significantly higher degrees of phosphorylation because of higher nuclear protein kinase activity (71 .+-. 2.6 .mu. mol Pi/mg per min vs. 37 .+-. 1.9 .mu.mol Pi/mg per min in controls, P < 0.01). In vitro stimulation of RNA synthesis by NHP was enhanced by the addition of protein kinase and cyclic AMP findings suggest that stimulation of RNA synthesis in the myocardium of hyperthyroid rats is mediated by the nuclear NHP and is dependent on phosphorylation of these proteins by nuclear protein kinases.