Hypoxia induces caspase-9 and caspase-3 activation without neuronal death in gerbil brains

被引:22
|
作者
Garnier, P
Prigent-Tessier, A
Van Hoecke, M
Bertrand, N
Demougeot, C
Sordet, O
Swanson, RA
Marie, C
Beley, A
机构
[1] Fac Pharm, Lab Pharmacodynam & Physiol Pharmaceut, F-21079 Dijon, France
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
[3] Vet Affairs Med Ctr, San Francisco, CA USA
[4] Fac Med, INSERM U517, Dijon, France
关键词
apoptosis; brain ischemia; caspase activation; hypoxia; Mongolian gerbil; PARP-1; cleavage;
D O I
10.1111/j.1460-9568.2004.03551.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:937 / 946
页数:10
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