Hydrogen peroxide-induced apoptosis of HL-60 human leukemia cells is mediated by the oxidants hypochlorous acid and chloramines.

Hydrogen peroxide-induced apoptosis of HL-60 human leukemia cells is mediated by the oxidants hypochlorous acid and chloramines.
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过氧化氢诱导的 HL-60 人白血病细胞凋亡是由氧化剂次氯酸和氯胺介导的。

DOI:
10.1016/s0003-9861(02)00053-x
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发表时间:
2002
期刊:
Archives of biochemistry and biophysics.
影响因子:
--
通讯作者:
Burns,CPatrick
Burns,CPatrick
中科院分区:
--
文献类型:
--
作者:
Wagner,BrettA;Britigan,BradleyE;Reszka,KrzysztofJ;McCormick,MichaelL;Burns,CPatrick

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本研究旨在确定H2 O2/MPO/Cl−产生的HOCl是否是HL-60人白血病细胞中H2 O2程序性细胞死亡的近端介质。我们发现,正宗HOCl诱导HL-60细胞凋亡。添加蛋氨酸(HOCl清除剂)和从培养基中去除Cl−以防止HOCl的形成都抑制了H2 O2诱导的细胞凋亡。HL-60细胞在完全培养液中暴露于HOCl时发生凋亡,其通过HOCl与胺基反应产生氯胺,但在无胺HBSS中不受HOCl的影响,其中HOCl而不是氯胺可被检测到。真正的氯胺诱导细胞凋亡,在这个细胞系中的浓度依赖性的方式和浓度低于HOCl。全培养基暴露于HOCl 24小时将支持甲硫氨酸不可诱导的细胞凋亡,但不与2-硝基-5-硫代苯甲酸(TNB)反应,提高了最终诱导剂是由HOCl和氯胺形成的非氧化剂的可能性。我们的结论是H2 O2在含MPO的HL-60细胞中诱导凋亡的信号涉及可扩散氧化剂HOCl与胺产生氯胺和随后的非TNB反应产物的反应。
We set out to identify whether HOCl, which is generated from H2O2/MPO/Cl−, is a proximal mediator of H2O2programmed cell death in the HL-60 human leukemia cell. We found that authentic HOCl induces apoptosis in the HL-60 cell. Both the addition of methionine, an HOCl scavenger, and the removal of Cl−from the medium to prevent the formation of HOCl inhibited H2O2-induced apoptosis. HL-60 cells underwent apoptosis when exposed to HOCl in full medium, which gives rise to chloramines by the reaction of HOCl with amine groups, but not by HOCl in the amine-free HBSS, in which HOCl but not chloramines can be detected. Authentic chloramines induced apoptosis in this cell line in a concentration-dependent manner and at concentrations lower than HOCl. Full medium exposed to HOCl for 24h would support methionine noninhibitable apoptosis, but did not react with 2-nitro-5-thiobenzoic acid (TNB), raising the possibility that the final inducer is a nonoxidant formed from HOCl and chloramines. We conclude that the signal for apoptosis induced by H2O2in the MPO-containing HL-60 cell involves the reaction of the diffusible oxidant HOCl with amines producing chloramines and a subsequent non-TNB-reactive product.
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