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
中科院分区:
文献类型:
--
作者:
Kelley, EE;Wagner, BA;Burns, CP
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.