Maulik N, Goswami S, Galang N, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.
FEBS Lett. 1999 Jan 29;443(3):331-6. doi: 10.1016/s0014-5793(98)01719-0.
Acute ischemia followed by prolonged reperfusion has been shown to induce cardiomyocyte apoptosis. In this report, we demonstrate that myocardial adaptation to ischemia induced by repeated cyclic episodes of short-term ischemia each followed by another short duration of reperfusion reduced cardiomyocyte apoptosis and DNA fragmentation. This was associated with the induction of the expression of Bcl-2 mRNA and translocation and activation of NF-kappaB. Another transcription factor, AP-1, remained unaffected by repeated ischemia and reperfusion, but exhibited significant upregulation by a single episode of 30 min ischemia followed by 2 h of reperfusion. This activation of AP-1 was inhibited by a scavenger of oxygen free radicals, DMTU. Thirty minutes ischemia and 120 min reperfusion downregulated the induction of the expression of Bcl-2 mRNA, but moderately activated NF-kappaB binding activity. This was associated with an increased number of apoptotic cells and DNA fragmentation in cardiomyocytes which were attenuated by DMTU. The results of this study indicate that Bcl-2, AP-1 and NF-kappaB differentially regulate cardiomyocyte apoptosis mediated by acute ischemia and prolonged reperfusion.
急性缺血后再灌注时间延长已被证明可诱导心肌细胞凋亡。在本报告中，我们证明，通过短期缺血的反复循环发作（每次发作后再进行短时间再灌注）所诱导的心肌对缺血的适应性可减少心肌细胞凋亡和DNA片段化。这与Bcl-2 mRNA表达的诱导以及NF-κB的易位和激活有关。另一种转录因子AP-1不受反复缺血和再灌注的影响，但在单次30分钟缺血后再灌注2小时会出现显著上调。AP-1的这种激活被氧自由基清除剂DMTU抑制。30分钟缺血和120分钟再灌注下调了Bcl-2 mRNA表达的诱导，但适度激活了NF-κB结合活性。这与心肌细胞中凋亡细胞数量增加和DNA片段化有关，而DMTU可减轻这种情况。本研究结果表明，Bcl-2、AP-1和NF-κB对急性缺血和长时间再灌注介导的心肌细胞凋亡有不同的调节作用。
