Lin K T, Xue J Y, Nomen M, Spur B, Wong P Y
Department of Cell Biology, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084, USA.
J Biol Chem. 1995 Jul 14;270(28):16487-90. doi: 10.1074/jbc.270.28.16487.
Peroxynitrite (ONOO-), an anion and a potent oxidant, generated by the interaction of nitric oxide (NO) and superoxide is able to induce apoptosis in HL-60 human leukemia cells in a time- and concentration-dependent manner. Characteristic morphology of apoptosis can be observed 3 h after HL-60 cells are exposed to 10 microM ONOO-. Treatment of HL-60 cells with increasing concentrations of ONOO- from 1 to 100 microM confirms the concentration dependence of apoptosis as evidenced by: 1) degradation of nuclear DNA of these cells into integer multiples of approximately 200 base pairs; 2) colorimetric DNA fragmentation assay; and 3) evidence of condensation of chromatin and nuclear fragmentation shown by propidium iodide staining. Under the same conditions, peroxynitrite causes apoptosis in another transformed cell line, U-937 cells, but is ineffective at inducing apoptosis in normal endothelial cells derived from human umbilical cord and normal human peripheral blood mononuclear cells. This direct evidence of peroxynitrite inducing apoptosis implicated a new function of this potent oxidant.
过氧亚硝酸盐(ONOO-)是一种阴离子且是一种强氧化剂,由一氧化氮(NO)和超氧化物相互作用产生,它能够以时间和浓度依赖的方式诱导HL-60人白血病细胞凋亡。HL-60细胞暴露于10微摩尔的过氧亚硝酸盐3小时后,可观察到凋亡的特征性形态。用浓度从1微摩尔到100微摩尔递增的过氧亚硝酸盐处理HL-60细胞,证实了凋亡的浓度依赖性,证据如下:1)这些细胞的核DNA降解为约200个碱基对的整数倍;2)比色法DNA片段化分析;3)碘化丙啶染色显示的染色质凝聚和核碎裂证据。在相同条件下,过氧亚硝酸盐可导致另一种转化细胞系U-937细胞凋亡,但对源自人脐带的正常内皮细胞和正常人外周血单核细胞诱导凋亡无效。过氧亚硝酸盐诱导凋亡的这一直接证据表明了这种强氧化剂的一种新功能。