In Vitro Interaction Between Homocysteine and Copper Ions: Potential Redox Implications
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Homocysteine (Hcys) has been implicated in various oxidative stressâ€“related disorders. The presence of a thiol on its structure allows Hcys to exert a double-edge redox action. Depending on whether Cu2Ã¾ions occur concomitantly, Hcys can either promote or prevent free radical generation and its consequences. We have addressed in vitro the interaction between Hcys and Cu2Ã¾ ions, in terms of the consequences that such interaction may have on the free radical scavenging properties of Hcys and on the redox state and redox activity of the metal. To this end, we investigated the free radicalâ€“scavenging, O2 #1;#2;-generating, and ascorbate-oxidizing properties of the interacting species by assessing the bleaching of ABTS#1;Ã¾ radicals, the reduction of O2 #1;#2;-dependent cytochrome c, and the copper-dependent oxidation of ascorbate, respectively. In addition, electron paramagnetic resonance and Cu(I)-bathocuproine formation were applied to assess the formation of paramagnetic complexes and the metal redox state. Upon a brief incubation, the Hcys/Cu2Ã¾ interaction led to a decrease in the free radicalâ€“scavenging properties of Hcys, and to a comparable loss of the thiol density. Both effects were partial and were not modified by increasing the incubation time, despite the presence of Cu2Ã¾excess. Depending on the molar Hcys:Cu2Ã¾ ratio, the interaction resulted in the formation of mixtures that appear to contain time-stable and ascorbate-reducible Cu(II) complexes (for ratios up to 2:1), and ascorbate- and oxygen-redoxâ€“inactive Cu(I) complexes (for ratios up to 4:1). Increasing the interaction ratio beyond 4:1 was associated with the sudden appearance of an O2 #1;#2;-generating activity. The data indicate that depending on the molar ratio of interaction, Hcys and Cu2Ã¾ react to form copper complexes that can promote either antioxidant or pro-oxidant actions. We speculate that the redox activity arising from a large molar Hcys excess may partially underlie the association between hyperhomocysteinemia and a greater risk of developing oxidativerelated cardiovascular diseases.
This work was supported by FONDECYT (grant 1040736).
Quote ItemEXPERIMENTAL BIOLOGY AND MEDICINE Volume: 231 Issue: 9 Pages: 1569-1575