The cardioprotective agent urocortin induces expression of CT-1.
The corticotrophin-releasing hormone-related factor, urocortin (Ucn) and the interleukin (IL)-6 family cytokine cardiotrophin-1 (CT-1) are both cardioprotective agents able to protect the heart from ischemic damage. In both cases the protective effect involves activation of the p42/p44 MAPK and PI-3 kinase/Akt pathways, but the protective effect of Ucn requires de novo protein synthesis whereas that of CT-1 does not. In this study, we show that Ucn induces enhanced expression of CT-1 at both the mRNA and protein levels. This effect is mediated by activation of the CT-1 gene promoter and requires the transcription factor C/EBPbeta/NF-IL6. Hence, a specific cardioprotective factor can induce enhanced expression of another cardioprotective factor belonging to an unrelated protein family.
Janjua
Sadia
S
Institute of Child Health, University College London, London WC1N 1 EH, UK.
Lawrence
Kevin M
KM
Ng
Leong L
LL
Latchman
David S
DS
D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D008163:Luminescent Measurements; D009154:Mutation / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D054832:Urocortins
D016207:Cytokines; D054832:Urocortins; D012313:RNA; D003346:Corticotropin-Releasing Hormone; C092073:cardiotrophin 1; D008156:Luciferases