Nitric oxide reaction with lipid peroxyl radicals spares alpha-tocopherol during lipid peroxidation - Greater oxidant protection from the pair nitricoxide/alpha-tocopherol than alpha-tocopherol/ascorbate

Citation
H. Rubbo et al., Nitric oxide reaction with lipid peroxyl radicals spares alpha-tocopherol during lipid peroxidation - Greater oxidant protection from the pair nitricoxide/alpha-tocopherol than alpha-tocopherol/ascorbate, J BIOL CHEM, 275(15), 2000, pp. 10812-10818
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
275
Issue
15
Year of publication
2000
Pages
10812 - 10818
Database
ISI
SICI code
0021-9258(20000414)275:15<10812:NORWLP>2.0.ZU;2-M
Abstract
The reactions of nitric oxide ((NO)-N-.) and alpha-tocopherol (alpha-TH) du ring membrane lipid oxidation were examined and compared with the pair alph a-TH/ascorbate. Nitric oxide serves as a more potent inhibitor of lipid per oxidation propagation reactions than alpha-TH and protects alpha-TH from ox idation, Mass spectrometry, oxygen and (NO)-N-. consumption, conjugated die ne analyses, and alpha-TH fluorescence determinations all demonstrated that (NO)-N-. preferentially reacts with lipid radical species, with alpha-TH c onsumption not occurring until (NO)-N-. concentrations fell below a critica l level. In addition, alpha-TH and (NO)-N-. cooperatively inhibit lipid per oxidation, exhibiting greater antioxidant capacity than the pair alpha-TH/a scorbate. Pulse radiolysis analysis showed no direct reaction between (NO)- N-. and alpha-tocopheroxyl radical (alpha-T-.), inferring that peroxyl radi cal termination reactions are the principal lipid-protective mechanism medi ated by (NO)-N-.. These observations support the concept that (NO)-N-. is a potent chain breaking antioxidant toward peroxidizing lipids, due to facil e radical-radical termination reactions with lipid radical species, thus pr eventing alpha-TH loss. The reduction of alpha-T-. by ascorbate was a compa ratively less efficient mechanism for preserving alpha-TH than (NO)-N-.-med iated termination of peroxyl radicals, due to slower reaction kinetics and limited transfer of reducing equivalents from the aqueous phase. Thus, the high lipid/water partition coefficient of (NO)-N-., its capacity to diffuse and concentrate in lipophilic milieu, and a potent reactivity toward lipid radical species reveal how (NO)-N-. can play a critical role in regulating membrane and lipoprotein lipid oxidation reactions.