PMID:20933497

Citation	Takatani-Nakase, T and Takahashi, K (2010) Cardioprotective activity of urocortin by preventing caspase-independent, non-apoptotic death in cultured neonatal rat cardiomyocytes exposed to ischemia. Biochem. Biophys. Res. Commun. 402:216-21
Abstract	Caspase-independent, non-apoptotic cell death in ischemic heart disease is considered to be one of the important therapeutic targets, however, the detailed mechanisms of this cell death process are not clear. In this study, we investigated the mechanisms of non-apoptotic cell death in cultured neonatal rat cardiomyocytes during ischemia, and the cardioprotection by preventing the mechanisms. We found that ischemia caused elevation of the phospholipase A2 (iPLA2) expression in the myocytes, leading to distinctive non-apoptotic nuclear shrinkage, and cell death. Moreover, we investigated whether the potent cardioprotective corticotropin-releasing hormone (CRH), urocortin, which had been less focused on non-apoptotic cell death, inhibits the ischemic myocyte death. Ischemia-augmented nuclear shrinkage of the myocytes was suppressed by the pretreatment of ∼10 nM urocortin before the cells were exposed to ischemia. Urocortin could significantly suppress the expression and activity of iPLA2, resulting in preventing the ischemia-induced cell death. The survival-promoting effect of urocortin was abrogated by the CRH receptor antagonist astressin. These findings provide the first evidence linking the targets of the urocortin-mediated cardioprotection to the suppression of the caspase-independent, non-apoptotic death in cardiac myocytes exposed to ischemia.
Links	PubMed Online version:10.1016/j.bbrc.2010.10.001
Keywords	Animals; Apoptosis; Caspases/metabolism; Cells, Cultured; Cytoprotection; Myocardial Ischemia/enzymology; Myocardial Ischemia/pathology; Myocytes, Cardiac/drug effects; Myocytes, Cardiac/enzymology; Myocytes, Cardiac/pathology; Phospholipases A2, Calcium-Independent/antagonists & inhibitors; Phospholipases A2, Calcium-Independent/metabolism; Rats; Rats, Wistar; Urocortins/metabolism; Urocortins/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:UCN1	involved_in	GO:0060547: negative regulation of necrotic cell death	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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