Involvement of oxidative stress and caspase-3 in cortical infarction after photothrombotic ischemia in mice
Involvement of oxidative stress and caspase-3 in cortical infarction after photothrombotic ischemia in mice
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DOI：
10.1097/00004647-200012000-00008
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发表时间：
2000-12-01
影响因子：
6.3
通讯作者：
Chan, PH
中科院分区：
文献类型：
--
作者：
Kim, GW;Sugawara, T;Chan, PH
实验性脑缺血中凋亡相关的细胞死亡与氧化应激和半胱天冬酶有关。然而，氧化应激在脑缺血后半胱天冬酶激活和随后的凋亡细胞死亡中的作用尚不清楚。作者评价了氧化应激在光血栓形成后缺血性脑梗死中的作用，以及在有和无U-74389G（一种有效的自由基清除剂，10 mg/kg，缺血诱导前后30分钟）的情况下，缺血后6小时和24小时氧化应激与半胱天冬酶相关细胞死亡之间的关系。在早期缺血性病变中，氢乙啶氧化法检测到的活性氧和细胞色素c都有缺陷。Western blot分析显示缺血后24小时缺血损伤区caspase-3的裂解形式和水平增加。缺血后抗氧化剂治疗组caspase-3免疫反应性降低。与未治疗组相比，缺血后治疗组的DNA片段化和梯状化减少，病变较小。光血栓性缺血后，缺血性病变中发生氧化应激和细胞色素c释放。自由基清除剂减弱了caspase-3的上调、DNA片段化和最终病变。作者得出的结论是，氧化应激可能介导半胱天冬酶相关的细胞凋亡死亡和光血栓缺血后随后的皮质梗死。
Apoptosis-related cell death is linked to oxidative stress and caspases in experimental cerebral ischemia. However, the role of oxidative stress in caspase activation and subsequent apoptotic cell death after cerebral ischemia is unknown. The authors evaluated the role of oxidative stress in ischemic cerebral infarction after photothrombosis and the relation between oxidative stress and caspase-related cell death 6 and 24 hours after ischemia with and without U-74389G, a potent free radical scavenger (10 mg/kg, 30 minutes before and after ischemia induction). Reactive oxygen species, detected by hydroethidine oxidation, and cytosolic cytochrome c were defected in early ischemic lesions. Western blot analysis showed the cleaved form and the increased level of the preform of caspase-3 in the ischemic lesion 24 hours after ischemia. Decreased caspase-3 immunoreactivity was detected in the antioxidant-treated group after ischemia. Decreased DNA fragmentation and laddering were detected and the lesion was smaller in the treated group after ischemia compared with the untreated group. Oxidative stress and cytochrome c release occur in the ischemic lesion after photothrombotic ischemia. The free radical scavenger attenuated caspase-3 up-regulation, DNA fragmentation, and the final lesion. The authors concluded that oxidative stress may mediate caspase-related apoptotic cell death and subsequent cortical infarction after photothrombotic ischemia.