Giles Gregory I, Tasker Karen M, Collins Catriona, Giles Niroshini M, O'rourke Elizabeth, Jacob Claus
School of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
Biochem J. 2002 Jun 1;364(Pt 2):579-85. doi: 10.1042/BJ20011882.
We have recently proposed that disulphide S-monoxides (thiosulphinates) and disulphide S-dioxides (thiosulphonates) are formed from their parent disulphides and 'reactive oxygen species' during oxidative stress. These 'reactive sulphur species' are themselves strong oxidizing agents that preferably attack the thiol functionality. We now show that under conditions where disulphides show little effect, disulphide S-oxides rapidly modify metallothionein, alcohol and glyceraldehyde 3-phosphate dehydrogenases and a zinc finger-protein fragment in vitro. The known antioxidants ascorbate, NADH, trolox and melatonin are unable to inhibit this oxidation pathway and only an excess of the cellular redox-buffer glutathione quenches the disulphide S-oxide activity. These results suggest that, under conditions of oxidative stress, despite the presence of high concentrations of antioxidants, reactive sulphur species formation may occur and inhibit the function of thiol-dependent proteins. Such a characterization of the disulphide S-oxide-oxidation pathway might also account for some previously observed anomalies in protein oxidation.
我们最近提出，在氧化应激期间，二硫化物S - 单氧化物（硫代亚磺酸盐）和二硫化物S - 二氧化物（硫代磺酸盐）由其母体二硫化物和“活性氧物种”形成。这些“活性硫物种”本身就是强氧化剂，优先攻击硫醇官能团。我们现在表明，在二硫化物影响很小的条件下，二硫化物S - 氧化物在体外能迅速修饰金属硫蛋白、醇脱氢酶和甘油醛 - 3 - 磷酸脱氢酶以及一个锌指蛋白片段。已知的抗氧化剂抗坏血酸、NADH、托洛克斯和褪黑素无法抑制这种氧化途径，只有过量的细胞氧化还原缓冲剂谷胱甘肽才能淬灭二硫化物S - 氧化物的活性。这些结果表明，在氧化应激条件下，尽管存在高浓度的抗氧化剂，但仍可能形成活性硫物种并抑制硫醇依赖性蛋白质的功能。二硫化物S - 氧化物氧化途径的这种特征也可能解释一些先前观察到的蛋白质氧化异常现象。
