Role of -Tocopheroxyl Radical in the Initiation of Lipid Peroxidation in Human Low-Density Lipoprotein Exposed to Horse Radish Perox
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- 作者：Paul K. Witting ; Joanne M. Upston ; and Roland Stocker
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：February 11, 1997
- 年：1997
- 卷：36
- 期：6
- 页码：1251 - 1258
- 全文大小：168K
- 年卷期：v.36,no.6(February 11, 1997)
- ISSN：1520-4995
文摘
Heme-containing (per)oxidases including horse radishperoxidase (HRP)/H2O2 have beenshownto oxidatively modify isolated low-density lipoprotein (LDL) invitro and oxidized LDL is implicated inthe early events leading to atherosclerosis. The role of
-tocopherol (-TOH) in the oxidation of LDLby HRP/H2O2 is unclear, although-tocopheroxyl radical (-TO
), which is formedduring this process,can act as a chain transfer agent of lipid peroxidation in LDL. Bycombining HPLC and EPR spectroscopy,we hereby show that during HRP/H2O2-inducedoxidation of human LDL: (i) the accumulation ofcholesteryl linoleate hydroperoxides and hydroxides (CE-O(O)H) occursconcomitantly with the formationof -TO and consumption of -TOH in the absence ofother detectable organic (g 
2) radicals; (ii)therates of -TO formation and subsequent decay reflectthe rates of both -TOH consumption and CE-O(O)H accumulation; (iii) CE-O(O)H accumulation is directly dependent onthe level of endogenous-TOH, and vitamin E supplementation results in increased lipidoxidizability; (iv) the inhibition of HRPactivity by catalase plus urate results in a persistent-TO signal, the decay (t1/2 20 min) of which isaccompanied by continued accumulation of CE-O(O)H, with completecessation of lipid peroxidationupon loss of the chromanoxyl signal. These results demonstrate adirect correlation between -TOH/-TO and the extent ofHRP/H2O2-induced LDL lipid peroxidation, andthat this type of oxidativemodification can occur in the absence of g 2 radicalsother than -TO. Together, the resultssupporta role for tocopherol-mediated peroxidation but not the involvement ofa protein radical in the initiationof LDL lipid peroxidation induced byHRP/H2O2.
-tocopherol (-TOH) in the oxidation of LDLby HRP/H2O2 is unclear, although-tocopheroxyl radical (-TO), which is formedduring this process,can act as a chain transfer agent of lipid peroxidation in LDL. Bycombining HPLC and EPR spectroscopy,we hereby show that during HRP/H2O2-inducedoxidation of human LDL: (i) the accumulation ofcholesteryl linoleate hydroperoxides and hydroxides (CE-O(O)H) occursconcomitantly with the formationof -TO and consumption of -TOH in the absence ofother detectable organic (g 2) radicals; (ii)therates of -TO formation and subsequent decay reflectthe rates of both -TOH consumption and CE-O(O)H accumulation; (iii) CE-O(O)H accumulation is directly dependent onthe level of endogenous-TOH, and vitamin E supplementation results in increased lipidoxidizability; (iv) the inhibition of HRPactivity by catalase plus urate results in a persistent-TO signal, the decay (t1/2 20 min) of which isaccompanied by continued accumulation of CE-O(O)H, with completecessation of lipid peroxidationupon loss of the chromanoxyl signal. These results demonstrate adirect correlation between -TOH/-TO and the extent ofHRP/H2O2-induced LDL lipid peroxidation, andthat this type of oxidativemodification can occur in the absence of g 2 radicalsother than -TO. Together, the resultssupporta role for tocopherol-mediated peroxidation but not the involvement ofa protein radical in the initiationof LDL lipid peroxidation induced byHRP/H2O2.