Regulation of cardiomyocyte apoptosis by redox-sensitive transcription factors
Regulation of cardiomyocyte apoptosis by redox-sensitive transcription factors
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DOI：
10.1016/s0014-5793(00)02174-8
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发表时间：
2000-11-17
期刊：
影响因子：
3.5
通讯作者：
Das, DK
中科院分区：
文献类型：
--
作者：
Maulik, N;Sasaki, H;Das, DK
缺血心肌再灌注导致细胞凋亡和DNA断裂。已知几种转录因子可调控凋亡细胞的死亡。本研究旨在探讨这些转录因子对心肌细胞凋亡的调控作用。将离体工作大鼠心脏分为对照组、缺血15 min组、缺血60 min组、缺血15 min后再灌注2 h组、缺血应激适应组（4次循环至缺血15 min后再灌注10 min）、缺血15 min后再灌注2 h组，检测氧化还原调节的转录因子、NF κ b、AP-1和促凋亡基因Bel-2、p53的表达。结果表明，随着缺血时间的延长，NF - kappaB和AP-1逐渐稳定升高，在适应心肌中，NF - kappaB的结合保持在较高水平，而AP-1的结合则降至接近基线值。抗氧化基因Bcl-2在缺血/再灌注心肌中表达下调，而在预处理心肌中表达上调，缺血/再灌注后p53表达显著诱导，相同缺血/再灌注的适应心肌中几乎未检测到凋亡细胞。研究结果首次证实了心肌细胞凋亡受促凋亡和抗凋亡转录因子及基因调控的差异与缺血再灌注时间的长短有关。(C) 2000年欧洲生化学会联合会。Elsevier Science B.V.版权所有。
Reperfusion of ischemic myocardium results in apoptotic cell death and DNA fragmentation. Several transcription factors are known to regulate the apoptotic cell death. This study sought to examine the regulation of cardiomyocyte apoptosis by these transcription factors. Isotated working rat hearts were divided into six groups: control, 15 min ischemia, 60 min ischemia, 15 min ischemia followed by 2 h reperfusion, ischemic stress adaptation by subjecting the hearts to four cyclic episodes to 15 min ischemia, each followed by 10 min of reperfusion, and adaptation followed by 15 min ischemia and 2 h reperfusion, Redox-regulated transcription factors, NF kappaB and AP-1 and the expression of bro anti- and pro-apoptotic genes, Bel-2 and p53 were determined. The results demonstrated NF kappaB and AP-1 progressively and steadily increased as a function of the duration of ischemia, In the adapted heart, NF kappaB binding remained high while AP-1 binding was lowered to almost baseline value. The anti-oxidant gene, Bcl-2 was downregulated in the ischemic/reperfused heart, but upregulated in the preconditioned myocardium, Significant induction of the expression of p53 occurred after ischemia and reperfusion, Apoptotic cells were barely detected in the adapted myocardium which was subjected to the same ischemia/reperfusion protocol. The results demonstrate for the first time differential regulation of cardiomyocyte apoptosis by pro- and anti-apoptotic transcription factors and genes as a function of different durations of ischemia and reperfusion. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.