The selection between apoptosis and necrosis is differentially regulated in hydrogen peroxide-treated and glutathione-depleted human promonocytic cells
The selection between apoptosis and necrosis is differentially regulated in hydrogen peroxide-treated and glutathione-depleted human promonocytic cells
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DOI：
10.1038/sj.cdd.4401249
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发表时间：
2003-08-01
影响因子：
12.4
通讯作者：
Aller, P
中科院分区：
文献类型：
--
作者：
Troyano, A;Sancho, P;Aller, P
0.2 mM过氧化氢(H_2O_2)或0.5 mM顺铂作用于U-937人前单核细胞，可引起caspase-9和caspase-3的激活和死亡。然而，在用顺铂治疗之前，用2 mM的H_2O_2处理，或用谷胱甘肽抑制剂DL-丁硫氨酸-(S，R)-亚磺胺(BSO)孵育，可抑制caspase的激活，并使死亡模式变为坏死。2 mM H_2O_2处理细胞后，细胞内ATP水平显著下降，3-氨基苯甲酰胺(3-ABA)可部分抑制这种作用。相应地，3-ABA恢复了半胱氨酸天冬氨酸氨基转移酶的激活和凋亡的执行。相比之下，BSO+顺铂不降低细胞内ATP水平，3-ABA不影响该处理所致的细胞坏死。另一方面，虽然所有诱导细胞凋亡的处理和2 mM H_2O_2处理都引起Bax从胞浆向线粒体的移位，以及细胞色素c从线粒体向胞浆的释放，但BSO+顺铂处理没有。单独用顺铂处理会引起BID裂解，而BSO加顺铂以及0.2和2 mM的过氧化氢处理则不会。BCL-2过表达可减少H_2O_2诱导的细胞坏死，但不能减少BSO+顺铂诱导的细胞坏死。这些结果表明，在不同形式的氧化应激下，原单核细胞存在不同的凋亡/坏死调节机制。
Treatment with 0.2 mM hydrogen peroxide (H2O2) or with 0.5 mM cisplatin caused caspase-9 and caspase-3 activation and death by apoptosis in U-937 human promonocytic cells. However, treatment with 2 mM H2O2, or incubation with the glutathione suppressor DL-buthionine-(S,R)-sulfoximine (BSO) prior to treatment with cisplatin, suppressed caspase activation and changed the mode of death to necrosis. Treatment with 2 mM H2O2 caused a great decrease in the intracellular ATP level, which was partially prevented by 3-aminobenzamide (3-ABA). Correspondingly, 3-ABA restored the activation of caspases and the execution of apoptosis. By contrast, BSO plus cisplatin did not decrease the ATP levels, and the generation of necrosis by this treatment was not affected by 3-ABA. On the other hand, while all apoptosis-inducing treatments and treatment with 2 mM H2O2 caused Bax translocation from the cytosol to mitochondria as well as cytochrome c release from mitochondria to the cytosol, treatment with BSO plus cisplatin did not. Treatment with cisplatin alone caused Bid cleavage, while BSO plus cisplatin as well as 0.2 and 2 mM H2O2 did not. Bcl-2 overexpression reduced the generation of necrosis by H2O2, but not by BSO plus cisplatin. These results indicate the existence of different apoptosis/necrosis regulatory mechanisms in promonocytic cells subjected to different forms of oxidative stress.