谷胱甘肽
化学
三肽
硫醇
半胱氨酸
反应性(心理学)
氧化还原
氧化应激
活性氧
铜
生物化学
有机化学
氨基酸
酶
病理
医学
替代医学
作者
Enrico Falcone,Francesco Stellato,Bertrand Vileno,Merwan Bouraguba,Vincent Lebrun,Marianne Ilbert,Silvia Morante,Peter Faller
出处
期刊:Metallomics
[Oxford University Press]
日期:2023-06-23
卷期号:15 (7)
被引量:8
标识
DOI:10.1093/mtomcs/mfad040
摘要
Abstract Copper (Cu) is essential for most organisms, but it can be poisonous in excess, through mechanisms such as protein aggregation, trans-metallation, and oxidative stress. The latter could implicate the formation of potentially harmful reactive oxygen species (O2•−, H2O2, and HO•) via the redox cycling between Cu(II)/Cu(I) states in the presence of dioxygen and physiological reducing agents such as ascorbate (AscH), cysteine (Cys), and the tripeptide glutathione (GSH). Although the reactivity of Cu with these reductants has been previously investigated, the reactions taking place in a more physiologically relevant mixture of these biomolecules are not known. Hence, we report here on the reactivity of Cu with binary and ternary mixtures of AscH, Cys, and GSH. By measuring AscH and thiol oxidation, as well as HO• formation, we show that Cu reacts preferentially with GSH and Cys, halting AscH oxidation and also HO• release. This could be explained by the formation of Cu-thiolate clusters with both GSH and, as we first demonstrate here, Cys. Moreover, we observed a remarkable acceleration of Cu-catalyzed GSH oxidation in the presence of Cys. We provide evidence that both thiol-disulfide exchange and the generated H2O2 contribute to this effect. Based on these findings, we speculate that Cu-induced oxidative stress may be mainly driven by GSH depletion and/or protein disulfide formation rather than by HO• and envision a synergistic effect of Cys on Cu toxicity.
科研通智能强力驱动
Strongly Powered by AbleSci AI