Overexpression of IAP-2 attenuates apoptosis and protects against myocardial ischemia/reperfusion injury in transgenic mice
Overexpression of IAP-2 attenuates apoptosis and protects against myocardial ischemia/reperfusion injury in transgenic mice
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DOI：
10.1016/j.bbamcr.2007.01.007
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发表时间：
2007-04-01
影响因子：
5.1
通讯作者：
Chua, Balvin H. L.
中科院分区：
文献类型：
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作者：
Chua, Chu Chang;Gao, Jinping;Chua, Balvin H. L.
凋亡抑制蛋白（IAP）是caspase-3和-7的关键内在调节因子。在缺血期间，IAP-2显著上调，而其他IAP显示很少或没有变化。为了测试IAP-2是否防止缺血/再灌注后的心脏凋亡和损伤，我们产生了一系列携带小鼠IAP-2转基因的转基因小鼠。转基因小鼠心脏中表达高水平的小鼠IAP-2转录物和70 kDa IAP-2，而IAP-1和XIAP水平保持不变。免疫组织化学研究显示转基因小鼠心肌细胞中IAP-2的染色更强烈。为了评估IAP-2在I/R损伤中的作用，对转基因小鼠进行左冠状动脉前降支结扎，然后再灌注。转基因小鼠的梗死面积（以危险区域的百分比表示）明显小于非转基因小鼠（分别为30 +/- 2%和44 +/-2%，P
Inhibitors of apoptosis proteins (IAPs) are key intrinsic regulators of caspases-3 and -7. During ischemia, IAP-2 is upregulated dramatically, while the other IAPs show little or no change. To test whether IAP-2 prevents cardiac apoptosis and injury following ischemia/reperfusion, we generated a line of transgenic mice that carried a mouse IAP-2 transgene. High levels of mouse IAP-2 transcripts and 70 kDa IAP-2 were expressed in the hearts of transgenic mice, whereas IAP-1 and XIAP levels remained the same. Immunohistochemical studies revealed more intense staining of IAP-2 in the myocytes of transgenic mouse hearts. To assess the role of IAP-2 in I/R injury, the transgenic mice were subjected to ligation of the left descending anterior coronary artery ligation followed by reperfusion. The infarct sizes, expressed as the percentage of the area at risk, were significantly smaller in the transgenic mice than in the non-transgenic mice (30 +/- 2% vs. 44 +/- 2%, respectively, P