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.
- disulphide S-oxides
- oxidative stress
- reactive sulphur species
- sulphur proteins
↵1 These authors contributed equally to this work.
Abbreviations used: ADH, alcohol dehydrogenase; C1, cystamine S-monoxide; C2, glutathione disulphide S-dioxide; CDNB, 1-chloro-2,4-dinitrobenzene; DTNB, 5,5′-dithiobis-(2-nitrobenzoic acid); GAP, glyceraldehyde 3-phosphate; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GPx, glutathione peroxidase; GST, glutathione S-transferase; MT, metallothionein; PAR, 4-(2-pyridylazo)resorcinol; ROS, reactive oxygen species; RSS, reactive sulphur species; ZFP, zinc finger protein.
- The Biochemical Society, London ©2002