Regulation of Ribosomal DNA Transcription During Cardiomyocyte Hypertrophy

Cardiomyocyte hypertrophy, induced by norepinephrine, endothelin-I, and contraction, is associated with increased rates of protein synthesis and reexpression of genes associated with the fetal gene program. The signal transduction pathways that link these stimuli to alterations in phenotype and protein accumulation are poorly understood. The increased rate of protein synthesis associated with cardiac hypertrophy is facilitated by an increase in the rate of transcription of the ribosomal genes (rDNA).We have demonstrated that norepinephrine or contraction-induced changes in the expression of an rDNA transcription factor, UBF, can account for the increased rates of rDNA transcription. Endothelin-1 stimulated the phosphorylation of UBF but not the cellular content of UBF. These results suggest that norepinephrine or contraction and endothelin-1 modulate both ribosome biogenesis and cardiomyocyte hypertrophy via different signal transduction pathways.