REGULATION OF RDNA TRANSCRIPTION FACTORS DURING CARDIOMYOCYTE HYPERTROPHY INDUCED BY ADRENERGIC AGENTS

Ribosomal DNA transcription is important to the regulation of cardiomyocyte ribosome content and, as a consequence, the rate of protein synthesis and accumulation during cardiac hypertrophy. We studied the regulation of ribosomal RNA synthesis and the levels of RNA polymerase I and the ribosomal DNA transcription factor, UBF, during norepinephrine-induced hypertrophy of contraction-arrested neonatal cardiomyocytes in culture. Nuclear run-on assays and Western blots demonstrated that, concomitant with hypertrophy, norepinephrine (1 mu M) increased the rate of ribosomal DNA transcription, without causing an increase in the amount of RNA polymerase I. However, the elevated rate of rRNA synthesis was accompanied by an increased cellular content of UBF protein as determined by Western analysis. Northern blots demonstrated norepinephrine-induced increases in UBF mRNA in neonatal cardiomyocytes indicating that the response was regulated, at least in part, at the pretranslational stage. Both alpha- and beta-adrenergic agents increased the level of UBF mRNA. The beta-adrenergic response was mimicked by forskolin (1 mu M) and the cyclic AMP analog dibutyryl cAMP (10 mu M). However, activation of protein kinase C by phorbol 12-myristate 13-acetate (0.1 mu M) did not increase expression of UBF. These results implicate UBF as a possible regulatory factor of the accelerated rDNA transcription observed during norepinephrine-mediated cardiomyocyte hypertrophy.