Identification of PKC Isoform-Specific Effects in Cardiac

Members of the mammalian protein kinase C (PKC) superfamily play key regulatory roles in multiple cellular processes. In the heart, PKC signaling is involved in hypertrophic agonist-in-duced gene expression and hypertrophic growth. To investi-gate the specific function of PKC signaling in regulating cardi-omyocyte growth, we used antisense oligonucleotides to inhibit PKC , the major isozyme present in the neonatal heart. Trans-fection of cultured neonatal cardiomyocytes with antisense PKC oligonucleotides resulted in a marked reduction in both PKC mRNA and protein levels. PKC antisense treatment also reduced phenylephrine (PE)-induced PKC activity and perinu-clear translocation of PKC. Antisense inhibition of PKC led to reduction of PE-induced increase in skeletal -actin mRNA levels and atrial natriuretic peptide (ANP) secretion but had n