Interplay of Oxygen, Vitamin E, and Carotenoids in Radical Reactions following Oxidation of Trp and Tyr Residues in Native HDL3 Apolipoproteins. Comparison with LDL. A Time-Resolved Spectro

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• 作者：Agn&egrave ; s Boullier ; Jean-Claude Mazi&egrave ; re ; Paulo Filipe ; Larry K. Patterson ; David M. Bartels ; Gordon L. Hug ; Joã ; o P. Freitas ; René ; Santus ; ^O ; Patrice Morli&egrave ; re
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：May 1, 2007
• 年：2007
• 卷：46
• 期：17
• 页码：5226 - 5237
• 全文大小：331K
• 年卷期：v.46,no.17(May 1, 2007)
• ISSN：1520-4995

文摘

It has been recently shown that the inhibition of apolipoprotein A-I (apoAI) reverse cholesteroltransport activity during oxidation of HDL by myeloperoxidase may involve myeloperoxidase electrontransfer pathways other than those leading to tyrosine chlorination. To better understand how suchmechanisms might be initiated, the role of semioxidized Tyr and Trp residues in loss of apoAI andapolipoprotein A-II (apoAII) integrity has been assessed using selective Trp and Tyr one-electron oxidationby Br₂^- radical-anions in HDL₃ as well as in unbound apoAI and apoAII. Behavior of these radicals inapolipoprotein B of LDL has also been assessed. Formation of semioxidized Tyr in HDL₃ is followed bypartial repair during several milliseconds via reaction with endogenous -tocopherol to form the-tocopheroxyl radical. Subsequently, 2% of -tocopheroxyl radical is repaired by HDL₃ carotenoids.With LDL, a faster repair of semioxidized Tyr by -tocopherol is observed, but carotenoid repair of-tocopheroxyl radical is not. Only a small fraction of HDL₃ particles contains -tocopherol and carotenoids,which explains limited repair of semioxidized Tyr by -tocopherol. All LDL particles normally containmultiple -tocopherol and carotenoid molecules, and the lack of repair of -tocopheroxyl radical bycarotenoids probably results from hindered mobility of carotenoids in the lipid core. Western blots of-irradiated HDL₃ comparable to those reported for apoAI myeloperoxidase oxidation show that theincomplete repair of semioxidized Tyr and Trp induces apoAI and apoAII permanent damage includingformation of a heterodimer of one apoAI with a monomeric apoAII at about 36 kDa.