Cardiotrophin-1 reduces stress-induced heat shock protein production in cardiac myocytes

Cardiotrophin-1 (CT-1) can induce expression of the protective heat shock p roteins (hsps) in cardiac cells. We show here that, unlike the stress induc ed accumulation of hsps, the effect of CT-1 is not accompanied by increased hsp mRNA levels and is insensitive to the RNA synthesis inhibitor actinomy cin D, suggesting that it occurs at the post-transcriptional level. Pre-tre atment with CT-1 reduces the ability of heat shock to induce hsp expression and this effect occurs at the transcriptional level. Hence, CT-1 and stres s induce the hsps via different pathways which can antagonise one another. The mechanisms of these effects and their potential impact on the use of CT -1 as a cardioprotective agent are discussed. (C) 2000 Academic Press.