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 protective and hypertrophic effects in the heart. Previous studies have shown that CT-1 treatment increases heat shock protein 70 (hsp70) and heat shock protein 90 (hsp90) levels in cardiac cells. Due to the known protective effects of hsp90 and hsp70, induction of these proteins may be involved in the protective 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 treatment at both the mRNA and protein levels. It has been demonstrated previously that, unlike hsp70 and hsp90, hsp56 overexpression does not protect cardiac myocytes against stressful stimuli. The other known effect of CT-1 is hypertrophy, an increase in cell size without cell division, which occurs in many cardiac pathologies. We investigated the role of hsp56 in the hypertrophic response of primary neonatal rat cardiac myocytes, using overexpression with transiently transfected plasmid vectors and Herpes viral vectors. Overexpression of hsp56 caused a significant increase in cardiac cell size and protein:DNA ratio. Hsp27, hsp70 and hsp90 overexpression had no effect on cell size. An antisense construct to hsp56 reduced hsp56 levels when transiently transfected and blocked the hypertrophic effect of CT-1. This is the first time that a hypertrophic effect has been demonstrated for a heat shock protein and demonstrates that CT-1-induced hypertrophy involves a specific hsp, which is not involved in its protective effect.
Railson
J E
JE
Medical Molecular Biology Unit, The Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Lawrence
K
K
Buddle
J C
JC
Pennica
D
D
Latchman
D S
DS
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics; D018259:Herpesvirus 1, Human; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011506:Proteins; D004247:DNA; C092073:cardiotrophin 1; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4; D016559:Tacrolimus