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.