tailieunhanh - Báo cáo Y học: Anti- and pro-oxidant effects of urate in copper-induced low-density lipoprotein oxidation

We reported earlier that urate may behave as a pro-oxidant in Cu 2+ -induced oxidation of diluted plasma. Thus,its effect on Cu 2+ -induced oxidation of isolated low-density lipoprotein (LDL) was investigated by mon-itoring the formation of malondialdehyde and conjugated dienes and the consumption of urate and carotenoids. We show that urate is antioxidant at high concentration but pro-oxidant at low concentration. | Eur. J. Biochem. 269 5474-5483 2002 FEBS 2002 doi Anti- and pro-oxidant effects of urate in copper-induced low-density lipoprotein oxidation Paulo Filipe1 2 Josiane Haigle3 Joao Freitas1 2 Afonso Fernandes1 Jean-Claude Maziere4 Cecile Maziere4 Rene Santus3 5 and Patrice Morliere3 5 1 Centro de Metabolismo e Endocrinologia Faculdade de Medicina de Lisboa Portugal 2Clinica Dermatológica Universitária Faculdade de Medicina de Lisboa Hospital de Santa Maria Lisbon Portugal 3Laboratoire de Photobiologie Museum National d Histoire Naturelle Paris France 4Laboratoire de Biochimie Universite de Picardie Jules Verne CHRU Amiens Hopital Nord Amiens France 5INSERM Institut de Recherche sur la Peau Hopital Saint-Louis Paris France We reported earlier that urate may behave as a prooxidant in Cu2 -induced oxidation of diluted plasma. Thus its effect on Cu2 -induced oxidation of isolated low-density lipoprotein LDL was investigated by monitoring the formation of malondialdehyde and conjugated dienes and the consumption of urate and carotenoids. We show that urate is antioxidant at high concentration but pro-oxidant at low concentration. Depending on Cu2 concentration the switch between the pro- and antioxidant behavior of urate occurs at different urate concentrations. At high Cu2 concentration in the presence of urate superoxide dísmuta and lềiTÌcytochrome c protect LDL from oxidation but no protection is observed at low Cu2 concentration. The use of Cu2 or Cu chelators demonstrates that both copper redox states are required. We suggest that two mechanisms occur depending on the Cu2 concentration. Urate may reduce Cu2 to Cu which in turn contributes to O2 formation. The Cu2 reduction is likely to produce the urate radical UH - . It is proposed that at high Cu2 concentration the reaction of UH - radical with O2- generates products or intermediates which trigger LDL oxidation. At low Cu 2 concentration we suggest that the Cu ions formed .