Valentim Lauren, Laurence Kevin M, Townsend Paul A, Carroll Christopher J, Soond Surinder, Scarabelli Tiziano M, Knight Richard A, Latchman David S, Stephanou Anastasis
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
J Mol Cell Cardiol. 2006 Jun;40(6):846-52. doi: 10.1016/j.yjmcc.2006.03.428. Epub 2006 May 12.
Autophagy is known to be a feature of cardiomyopathies 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 Beclin1 in autophagocytosis, reduction of Beclin1 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 Beclin1 expression, an effect which is mediated by activation of the PI3 kinase/Akt pathway but which does not involve activation of p42/p44 MAPK.
自噬是已知的心肌病和慢性缺血的一个特征。在此我们证明，自噬也可由单次缺血/再灌注（新生和成年大鼠心肌细胞中的I/R）诱导。与Beclin1在自噬作用中的关键作用一致，RNA干扰降低心肌细胞中Beclin1的表达可减少I/R诱导的自噬，这与细胞存活率提高相关。尿皮质素也可减少自噬，尿皮质素是一种内源性心脏肽，我们之前已表明它可减少I/R诱导的其他形式的心肌细胞死亡。尿皮质素对自噬的抑制部分是通过抑制Beclin1的表达介导的，这一效应是由PI3激酶/Akt途径的激活介导的，但不涉及p42/p44 MAPK的激活。
