Hypoxia induces caspase-9 and caspase-3 activation without neuronal death in gerbil brains
Hypoxia induces caspase-9 and caspase-3 activation without neuronal death in gerbil brains
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DOI：
10.1111/j.1460-9568.2004.03551.x
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发表时间：
2004-08-01
影响因子：
3.4
通讯作者：
Beley, A
中科院分区：
文献类型：
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作者：
Garnier, P;Prigent-Tessier, A;Beley, A
为了研究缺氧脑的体内凋亡机制，我们检测了蒙古沙鼠海马中caspase-9和caspase-3的表达，这些鼠分别在短暂缺氧（4% O-2持续6分钟）或前脑缺血（10分钟双侧颈动脉闭塞）后进行8小时至7天的再氧或血液再循环。通过分离海马基因组DNA和分析DNA片段以及包括TUNEL测定和脑切片甲苯胺蓝染色在内的组织学研究来表征凋亡性死亡。结果表明，缺氧和缺血沙鼠脑均表现出caspase-9和caspase-3基因表达的增加。然而，缺氧后未检测到细胞损伤，而缺血后观察到明显的DNA断裂和广泛的细胞死亡。此外，虽然缺氧不会导致细胞死亡，但缺氧和缺血都与procaspase-9和procaspase-3的裂解及其活性的增加以及caspase-3的主要底物聚（adp -核糖）聚合酶1 （PARP-1）的裂解有关。这些结果表明，在体内，即使是晚期凋亡事件，如缺氧脑中的caspase激活和PARP-1切割，也不一定会诱导凋亡神经元死亡的不可逆承诺。
To investigate the in vivo apoptotic machinery in oxygen deprived brain, we examined the expression of caspase-9 and caspase-3 in the hippocampus of Mongolian gerbils subjected to either transient hypoxia (4% O-2 for 6 min) or forebrain ischemia (10 min bilateral carotid artery occlusion) followed by 8 h to 7 days of reoxygenation or blood recirculation. Apoptotic death was characterized by isolating hippocampal genomic DNA and analysing DNA fragmentation as well as histological studies including TUNEL assay and toluidine blue staining of brain sections. The results showed that both hypoxic and ischemic gerbil brains exhibited an increase in caspase-9 and caspase-3 gene expression. However, no cell damage was detectable following hypoxia, while marked DNA fragmentation and extensive cell death was observed following ischemia. Moreover, although hypoxia did not lead to cell death, both hypoxia and ischemia were associated with cleavage of procaspase-9 and procaspase-3 and increases in their activities as well as cleavage of poly(ADP-ribose) polymerase-1 (PARP-1), a major caspase-3 substrate. These results indicate that, in vivo, even late apoptotic events such as caspase activation and PARP-1 cleavage in hypoxic brains do not necessarily induce an irreversible commitment to apoptotic neuronal death.