Reactive sulphur species: an in vitro investigation of the oxidation properties of disulphide S-oxides

Abstract

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.

Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion

“…The sulfhydryl moiety of cysteine readily interacts with prooxidants resulting in the oxidation to sulfenic, sulfinic, and sulfonic acid and in the formation of disulfide and mixed disulfide bonds (25)(26)(27). Of these modifications, sulfenic acids and disulfide bonds are reversible upon treatment with the reducing agent DTT.…”

Disulfide S-Monoxides Convert Xanthine Dehydrogenase into Oxidase in Rat Liver Cytosol More Potently Than Their Respective Disulfides

“…However, redox activation of the disulfide bond by oxidizing species to form disulfide S-monoxides has been suggested in vivo. [2][3][4] The present findings that disulfide S-monoxides can form large amounts of ROS via interconversion of XD into XO imply that the capacity to return disulfides to thiols, rather than formation of S-oxides, determines whether oxidative stress damage progresses or is arrested.…”

“…[2][3][4] The physiological and pathophysiological roles of disulfide S-monoxides in the body have attracted much attention. 5,6) It is known that xanthine oxidase/xanthine dehydrogenase (XO/XD) catalyzes the conversion of hypoxanthine into xanthine and xanthine into uric acid during normal biochemical events.…”

Schwefel und Selen: Bedeutung der Oxidationsstufe für Struktur und Funktion von Proteinen

“…Disulfide wie Cystamin und GSSG sind leicht zu Disulfid-Soxiden oxidierbar. [53,54] Diese "aktivierten" Disulfide reagieren schnell mit Thiolen in Proteinen und Enzymen und inaktivieren diese. Mit Disulfid-S-oxiden steht ein auf Cystein beruhender Weg zur Verfügung, der auf Redoxkaskaden hinausläuft, an denen Sulfen-und Sulfinsäuren sowie eine Glutathionylierung von Proteinen beteiligt sind.…”