Heat shock protein-56 is induced by cardiotrophin-1 and mediates its hypertrophic effect

Cardiotrophin-1 (CT-1) is an interleukin-6 family cytokine with known prote ctive and hypertrophic effects in the heart. Previous studies have shown th at CT-1 treatment increases heat shock protein 70 (hsp70) and heat shock pr otein 90 (hsp90) levels in cardiac cells. Due to the known protective effec ts of hsp90 and hsp70, induction of these proteins may be involved in the p rotective effects of CT-1. We show here that heat shock protein 56 (hsp56), also known as FK506 binding protein 59 (FKBP59), is induced by CT-1 treatm ent at both the mRNA and protein levels. It has been demonstrated previousl y that, unlike hsp70 and hsp90, hsp56 overexpression does not protect cardi ac myocytes against stressful stimuli. The other known effect of CT-1 is hy pertrophy, an increase in cell size without cell division, which occurs in many cardiac pathologies. We investigated the role of hsp56 in the hypertro phic response of primary neonatal rat cardiac myocytes, using overexpressio n with transiently transfected plasmid vectors and Herpes viral vectors. Ov erexpression of hsp56 caused a significant increase in cardiac cell size an d protein:DNA ratio. Hsp27, hsp-70 and hsp90 overexpression had no effect o n cell size. An antisense construct to hsp56 reduced hsp56 levels when tran siently transfected and blocked the hypertrophic effect of CT-1. This is th e first time that a hypertrophic effect has been demonstrated for a heat sh ock protein and demonstrates that CT-1-induced hypertrophy involves a speci fic hsp. which is not involved in its protective effect. (C) 2001 Academic Press.