Cardiotrophin-1 reduces stress-induced heat shock protein production in cardiac myocytes.
Cardiotrophin-1 (CT-1) can induce expression of the protective heat shock proteins (hsps) in cardiac cells. We show here that, unlike the stress induced accumulation of hsps, the effect of CT-1 is not accompanied by increased hsp mRNA levels and is insensitive to the RNA synthesis inhibitor actinomycin D, suggesting that it occurs at the post-transcriptional level. Pre-treatment 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 stress 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.
Railson
J
J
Institute of Child Health, 30 Guilford Street, London, WC1 N1EH, UK.
Lawrence
K
K
Stephanou
A
A
Brar
B
B
Pennica
D
D
Latchman
D
D
D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological; D013997:Time Factors; D014158:Transcription, Genetic
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D012313:RNA; C092073:cardiotrophin 1