Here , we show that in rat neonatal ventricular cardiomyocytes , activation of NF kappaB is involved in the hypertrophic response induced by myotrophin , a hypertrophic activator identified from spontaneously hypertensive rat heart and cardiomyopathic human hearts . ^^^ Myotrophin treatment stimulated NF kappaB nuclear translocation and transcriptional activity , accompanied by IkappaB alpha phosphorylation and degradation . ^^^ Consistently , myotrophin induced NF kappaB activation was enhanced by wild type IkappaB kinase ( IKK ) beta and abolished by the dominant negative IKKbeta or a general PKC inhibitor , calphostin C . ^^^ Importantly , myotrophin induced expression of two hypertrophic genes ( atrial natriuretic factor [ ANF ] and c myc ) and also enhanced protein synthesis were partially inhibited by a potent NF kappaB inhibitor , pyrrolidine dithio carbamate ( PDTC ) , and calphostin C . ^^^ These findings suggest that the PKC IKK NF kappaB pathway may play a critical role in mediating the myotrophin induced hypertrophic response in cardiomyocytes . . ^^^ |