title: Reactive sulphur species in oxidative signal transduction.
abstract: Intense interest has been generated by the discovery that reactive oxygen species can function as intracellular second messengers. Reactive oxygen species have been implicated in diverse cellular processes, including growth factor signal transduction, gene expression and apoptosis. Additionally, there is evidence for proteins that are regulated by redox environment through the reversible oxidation of their cysteine residues. However, the direct reaction of reactive oxygen species with cysteine at physiological concentrations is generally a slow process, suggesting that intermediates are required to convey efficiently the oxidative stimulus. Here, we discuss the evidence that DSOs (disulphide-S-oxides) are formed from glutathione under oxidizing conditions and specifically modulate the redox status of thiols, indicating the existence of specialized cellular oxidative pathways. DSO inactivated glyceraldehyde 3-phosphate and alcohol dehydrogenases and released zinc from metallothionein and a zinc finger domain. In contrast, equivalent concentrations of H(2)O(2) showed minimal effect. The antioxidants ascorbate, NADH, trolox and melatonin were unable to quench DSO-induced oxidation. These findings support the paradigm of oxidative signal transduction and provide a general pathway whereby reactive oxygen species can convert thiols into disulphides.
authors.affiliation: Exeter Biocatalysis Centre, School of Biological and Chemical Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. GregoryGiles@uab.edu
authors.forename: C
authors.initials: C
authors.lastname: Jacob
authors.forename: J R
authors.initials: JR
authors.lastname: Lancaster
authors.forename: G I
authors.initials: GI
authors.lastname: Giles
mesh_terms: D004220:Disulfides / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D004220:Disulfides; D013438:Sulfhydryl Compounds; D005978:Glutathione