Nitric oxide inhibits iron-induced lipid peroxidation in HL-60 cells

Nitric oxide inhibits iron-induced lipid peroxidation in HL-60 cells
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DOI:
10.1006/abbi.1999.1386
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发表时间:
1999-10-01
影响因子:
3.9
通讯作者:
Burns, CP
Burns, CP
中科院分区:
生物学3区
文献类型:
--
作者:
Kelley, EE;Wagner, BA;Burns, CP

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一氧化氮((NO)-N-.)可以保护细胞免受活性氧的有害影响。使用低密度脂蛋白以及模型系统,已证明(NO)-N-。可作为断链抗氧化剂,抑制脂质过氧化反应。为了检验假设(NO)-N-。可以作为细胞膜中的断链抗氧化剂,我们研究了(NO)-N-的影响。本实验用铁离子(20 μ M Fe ~(2+))对HL-60细胞进行氧化应激处理,观察细胞内氧的消耗情况,用(NO)-N ~-抑制氧的消耗。作为饱和水溶液。(NO)-N-抑制氧消耗的持续时间。在0.4-1.8 μ M范围内呈浓度依赖性。(NO)-N-的加入。在过氧化反应开始前加入Fe ~(2+),可延缓过氧化反应的发生,加入Fe ~(2+)前时间越近,抑制作用越长。在加入Fe 2+之前,通过D,L-丁硫氨酸-S,R-亚砜亚胺消耗细胞谷胱甘肽水平,导致氧消耗的初始速率更快,(NO)-N-的时间更短。诱导抑制氧消耗。使用硫代巴比妥酸反应物质作为标记物对铁诱导的脂质过氧化作用进行的补充研究也证明了(NO)-N-的保护作用,这种保护细胞免受脂质过氧化作用也表现为台盼蓝摄取的减少,这一观察结果证明了(NO)-N-的保护作用。对膜完整性的影响我们得出结论,(NO)-N-。保护HL-60人白血病细胞免受脂质过氧化,并且这种保护改善了由Fe 2+和分子氧引发的氧化过程的毒性。(C)北京:科学出版社.
Nitric oxide ((NO)-N-.) can protect cells against the detrimental effects of reactive oxygen species. Using low-density lipoprotein as well as model systems, it has been demonstrated that (NO)-N-. can serve as a chain-breaking antioxidant to blunt lipid peroxidation. To test the hypothesis that (NO)-N-. can serve as a chain-breaking antioxidant in cell membranes, we examined the effect of (NO)-N-. on iron-induced lipid peroxidation in human leukemia cells, We exposed HL-60 cells to an oxidative stress (20 mu M Fe2+) and monitored the consumption of oxygen as a measure of lipid peroxidation, Oxygen consumption was arrested by the addition of (NO)-N-. as a saturated aqueous solution. The duration of inhibition of oxygen consumption by (NO)-N-. was concentration-dependent in the 0.4-1.8 mu M range, The inhibition ended upon depletion of (NO)-N-.. The addition of (NO)-N-. prior to initiation of peroxidation delayed the onset of peroxidation; the nearer in time it was before Fe2+ addition, the longer the inhibition. Depletion of cellular glutathione levels by D,L-buthionine-S,R-sulfoximine prior to Fe2+ addition resulted in a more rapid initial rate of oxygen depletion and a shorter time for the (NO)-N-.-induced inhibition of oxygen consumption. Complementary studies of this iron-induced lipid peroxidation, using thiobarbituric acid reactive substances as a marker, also demonstrated the protective effects of (NO)-N-., This protection of cells against lipid peroxidation also manifested itself as a reduction in trypan blue uptake, an observation demonstrating the protective effects of (NO)-N-. on membrane integrity. We conclude that (NO)-N-. protects HL-60 human leukemia cells from lipid peroxidation and that this protection ameliorates the toxicity of the oxidation processes initiated by Fe2+ and dioxygen. (C) 1999 Academic Press.