Arachidonic acid converts the glutathione depletion-induced apoptosis to necrosis by promoting lipid peroxidation and reducing caspase-3 activity in rat glioma cells

被引:33
作者
Higuchi, Y [1 ]
Yoshimoto, T [1 ]
机构
[1] Kanazawa Univ, Grad Sch Med Sci, Dept Mol Pharmacol, Kanazawa, Ishikawa 9208640, Japan
关键词
arachidonic acid; apoptosis; necrosis; glutathione depletion; lipid peroxidation; glioma cells;
D O I
10.1006/abbi.2002.2784
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intracellular glutathione (GSH) depletion induced by buthionine sulfoximine (BSO) caused cell death that seemed to be apoptosis in C6 rat glioma cells. Arachidonic acid (AA) promoted BSO-induced cell death by accumulating reactive oxygen species (ROS) or hydroperoxides. AA inhibited caspase-3 activation and internucleosomal DNA fragmentation during the BSO-induced GSH depletion. Furthermore, AA reduced intracellular ATP content, induced dysfunction of mitochondrial membrane and enhanced 8-hydroxy-2'-deoxyguanosine (S-OH-dG) production. There was significant increase of 12-lipoxygenase activity in the presence of AA under the BSO-induced GSH depletion in C6 cells. These results suggest that AA promotes cell death by changing to necrosis from apoptosis through lipid peroxidation initiated by lipid hydroperoxides produced by 12-lipoxygenase under the GSH depletion in C6 cells. Some ROS such as hydroperoxide produced by unknown pathway make hydroxy radicals and induce S-OH-dG formation in the cells. The conversion of apoptosis to necrosis may be a possible event under GSH depleted conditions. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:133 / 140
页数:8
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