Cu(I) availability paradoxically antagonizes antioxidant consumption and lipid peroxidation during the initiation phase of copper-induced LDL oxidation.
The incubation of isolated human low-density lipoprotein (LDL) with Cu(II) promoted extensive oxidation of both the lipid and protein moieties of the lipoprotein particle. When the Cu(II) to LDL molar ratio was equal or higher than 50, the removal of Cu(I) formed by the contemporary presence of the Cu(I) chelator bathocuproine disulphonate (BC) markedly accelerated the formation of end-products of lipid peroxidation. Moreover, the initial rate of Cu(II)-induced consumption of either endogenous antioxidants in LDL or free alpha-tocopherol in suspension was increased in the presence of BC, thus indicating that the continuous removal of Cu(I) enhanced both antioxidant consumption and LDL oxidation promoted by copper. Furthermore, the direct addition of Cu(I), together with Cu(II), to a suspension of isolated LDL efficiently delayed the onset of extensive lipid peroxidation and decreased the rate of antioxidant consumption. The latter effect, however, was detectable exclusively on LDL-associated alpha-tocopherol and not on alpha-tocopherol in suspension, thus suggesting that the competition between Cu(I) and Cu(II) was taking place at discrete sites associated with the LDL particle. Finally, the inclusion of Cu(I) in the incubation medium of LDL already undergoing extensive peroxidation did not inhibit but rather markedly stimulated the rate of peroxidation. Although apparently in contrast with the common view that Cu(I) and not Cu(II) is the real trigger species of LDL oxidation in the copper model, the results reported here indicate that the availability of Cu(I) during the initiation phase of LDL oxidation promoted by copper antagonizes both antioxidant consumption and the onset of extensive oxidation.
Bagnati
M
M
Department of Medical Sciences, University of Piemonte Orientale A. Avogadro, Novara, Italy.
Bordone
R
R
Perugini
C
C
Cau
C
C
Albano
E
E
Bellomo
G
G
D000328:Adult; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D019327:Copper Sulfate / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood*; D014810:Vitamin E / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D008077:Lipoproteins, LDL; D014810:Vitamin E; D003300:Copper; D019327:Copper Sulfate