Apoptotic vs nonapoptotic cytotoxicity induced by hydrogen peroxide
Apoptotic vs nonapoptotic cytotoxicity induced by hydrogen peroxide
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DOI：
10.1016/s0891-5849(96)00235-3
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发表时间：
1997-01-01
影响因子：
7.4
通讯作者：
Lichtenstein, A
中科院分区：
文献类型：
--
作者：
Gardner, AM;Xu, FH;Lichtenstein, A
评估了在宽浓度范围内过氧化氢（H2 O2）诱导的细胞毒性的调节。检测到三种不同的模式：最高浓度（>10 mM）迅速诱导坏死形式的死亡，其特征在于DNA消化的模糊模式和初级细胞质和质膜损伤的形态学证据;相反，10和5 mM H2 O2诱导的核酸内切体DNA消化2同时具有细胞毒性，靶细胞死亡与凋亡的形态学证据相关。放线菌酮、雌二醇、氨基苯甲酰胺（阿坝）、金精三羧酸和钙耗竭可抑制细胞凋亡。最低浓度的H2 O2（0.5和0.1 mM）诱导的延迟细胞毒性（在24或48小时），这是不相关的DNA梯状条带的形成或凋亡的形态学证据，但被阿坝抑制。BCL-2的强制表达诱导耐0.5和0.1 mM H2 O2，但对5和10 mM诱导的细胞毒性没有影响。在不存在钙或镁的情况下，将分离的细胞核暴露于H2 O2未能诱导核内切体片段化。这些数据表明，H2 O2诱导的细胞毒性的不同途径，可以区分其不同的浓度依赖性，BCL-2可以防止某些形式的H2 O2诱导的细胞毒性。版权所有（C）1996 Elsevier Science Inc.
The regulation of cellular cytotoxicity induced by hydrogen peroxide (H2O2) over a wide concentration range was assessed. Three distinct patterns were detected: the highest concentrations (>10 mM) rapidly induced a necrotic form of death characterized by smeared patterns of DNA digestion and morphological evidence of primary cytoplasm and plasma membrane damage; In contrast, 10 and 5 mM H2O2 induced endonucleosomal DNA digestion 2 concurrently with cytotoxicity and target cell death was associated with morphologic evidence of apoptosis. Apoptosis was inhibited by cycloheximide, emetine, aminobenzamide (ABA), aurintricarboxylic acid, and calcium depletion. The lowest concentrations of H2O2 (0.5 and 0.1 mM)-induced delayed cytotoxicity (at 24 or 48 hr), which was not associated with DNA ladder formation or morphologic evidence of apoptosis, but was inhibited by ABA. Enforced expression of BCL-2 induced resistance to 0.5 and 0.1 mM H2O2 but had no effect on cytotoxicity induced by 5 and 10 mM. Exposure of isolated nuclei to H2O2 in the absence of calcium or magnesium failed to induce endonucleosomal fragmentation. These data indicate that distinct pathways of H2O2-induced cytotoxicity can be distinguished by their different concentration dependences, and that BCL-2 can protect against some forms of H2O2-induced cytotoxicity. Copyright (C) 1996 Elsevier Science Inc.