TERT-BUTYL HYDROPEROXIDE KILLS CULTURED-HEPATOCYTES BY PEROXIDIZING MEMBRANE-LIPIDS
TERT-BUTYL HYDROPEROXIDE KILLS CULTURED-HEPATOCYTES BY PEROXIDIZING MEMBRANE-LIPIDS
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DOI：
10.1016/0003-9861(89)90122-7
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发表时间：
1989-03-01
影响因子：
3.9
通讯作者：
FARBER, JL
中科院分区：
文献类型：
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作者：
MASAKI, N;KYLE, ME;FARBER, JL
叔丁基氢过氧化氢对培养肝细胞的杀伤作用与该毒素代谢所引起的谷胱甘肽代谢和细胞内钙稳态的变化无关。去铁胺、铁络合剂、自由基清除剂酮甲基丁酸以及抗氧化剂N，N‘-二苯基-对苯二胺(DPPD)和邻苯二酚可阻止细胞死亡，但对谷胱甘肽或钙代谢没有影响。丙二醛是细胞脂质过氧化的结果，在丧失生存能力之前积累。防止脂质过氧化与防止细胞死亡是平行的。高达25µm的DPPD或1 mM的邻苯二酚不能阻止铁依赖、过氧化氢酶不敏感的叔丁基烷氧基的形成。因此，DPPD和邻苯二酚不会对杀死细胞并引发脂质过氧化的自由基物种进行解毒，这是一种附带现象。此外，脂质过氧化不能简单地作为细胞死亡的结果而被消除。结论：低浓度叔丁基氢过氧化氢(<1.0 mM)对培养的肝细胞具有致死性损伤作用，其损伤机制依赖于细胞内脂质的过氧化作用。
The killing of cultured hepatocytes by tert-butyl hydroperoxide was dissociated from the changes both in glutathione metabolism and in intracellular calcium homeostasis that accompany the metabolism of this toxin. Deferoxamine, a ferric iron chelator, ketomethiolbutyric acid, a radical scavenger, and the antioxidants N,N''-diphenyl-p-phenylenediamine (DPPD) and catechol prevented the cell killing without effect on glutathione or calcium metabolism. Malondialdehyde, formed as a result of the peroxidation of cellular lipids, accumulated before any loss of viability. Prevention of the lipid peroxidation paralleled the prevention of cell killing. As much as 25 .mu.M DPPD or 1 mM catechol did not prevent the iron-dependent, catalase-insensitive formation of tert-butyl alkoxyl radicals. Thus, DPPD and catechol do not detoxify a radical species that kills the cells and initiates lipid peroxidation as an epiphenomenon. Furthermore, lipid peroxidation cannot be dismissed as simply a consequence of the cell killing. It is concluded that low concentrations of tert-butyl hydroperoxide (less than 1.0 mM) lethally injure cultured hepatocytes by a mechanism that depends on the peroxidation of cellular lipids.