Urocortin protects against ischemic injury via a MAPK-dependent pathway.
Urocortin (UCN), is a peptide related to hypothalamic corticotrophin releasing hormone (CRF) and binds with high affinity to the CRF-R2 beta receptor which is expressed in the heart. UCN prevents cell death when administered to primary cardiac myocyte cultures both prior to simulated hypoxia/ischemia and at the point of reoxygenation after simulated hypoxia/ischemia as assayed by trypan blue exclusion. 3'-OH end labeling of DNA (TUNEL), annexin-V and fluorescence activated cell sorting. The protective effect of UCN is dependent on the p42/p44 mitogen-activated protein kinase (MAPK)-pathway. UCN also reduces damage in isolated rat hearts ex vivo, subjected to regional ischemia/reperfusion with the protective effect being observed when UCN is given either prior to ischemia or at the time of reperfusion after ischemia. Hence, UCN is a cardioprotective agent, which acts when given prior to ischemia or after ischemia at reperfusion.
Latchman
D S
DS
Institute of Child Health, University College London, London, United Kingdom.
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000627:therapeutic use*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D020011:Protective Agents / Q000378:metabolism* / Q000627:therapeutic use*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D054832:Urocortins
C101531:CRF receptor type 2; D020011:Protective Agents; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D020928:Mitogen-Activated Protein Kinases