期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 40, 期 6, 页码 846-852出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2006.03.428
关键词
autophagy; Beclin 1; ischaemia/reperfusion; urocortin; cell death; apoptosis; cardioprotection
Autophagy is known to be a feature of cardiorryopathies and chronic ischaemia. Here we demonstrate that autophagy is also induced by a single cycle of ischaemia/reperfusion (I/R in neonatal and adult rat cardiac myocytes). Consistent with the critical role for Beclin 1 in autophagocytosis, reduction of Beclin 1 expression in cardiac myocytes by RNAi reduces I/R-induced autophagy and this is associated with enhanced cell survival. Autophagy is also reduced by urocortin, an endogenous cardiac peptide which we have previously shown to reduce other forms of myocyte cell death induced by I/R. The inhibition of autophagy by urocortin is mediated in part by inhibition of Beclin 1 expression, an effect which is mediated by activation of the PI3 kinase/Akt pathway but which does not involve activation of p42/p44 MAPK. (c) 2006 Elsevier Inc. All rights reserved.
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