RESUMEN
Oxidative stress involves the generation of a number of reactive species, among them 'reactive oxygen species' and 'reactive nitrogen species'. Recent reports have indicated that disulfide-S-monoxides (thiosulfinates) and disulfide-S-dioxides (thiosulfonates) are formed under conditions of oxidative stress. We have now been able to demonstrate that these species are highly reactive and rapidly oxidise thiols. Glutathione and cysteine were oxidised to mixed disulfides by the action of disulfide-S-oxides. Oxidative attack on the zinc/sulfur protein metallothionein with concomitant zinc release was readily accomplished by these 'reactive sulfur species' whereas hydrogen peroxide showed minimal zinc release.
Asunto(s)
Disulfuros/química , Disulfuro de Glutatión/análogos & derivados , Óxidos/química , Compuestos de Sulfhidrilo/química , Azufre/química , Cisteína/química , Glutatión/química , Disulfuro de Glutatión/síntesis química , Peróxido de Hidrógeno/química , Metalotioneína/química , Oxidantes/química , Oxidación-Reducción , Estrés Oxidativo , Especies Reactivas de Oxígeno , Sensibilidad y EspecificidadRESUMEN
Oxidative stress arises from an imbalance in the metabolism of redox-active species promoting the formation of oxidizing agents. At present, these species are thought to include reactive oxygen, reactive nitrogen, and reactive nitrogen oxygen species (ROS, RNS, and RNOS, respectively). Reactive species have their origin in enzymatic synthesis, environmental induction, or by the further chemical reaction of an active species with other endogenous molecules to generate a second-generation reactive species. These second-generation species possess a different spectrum of activity to the parent species, with different redox reactions and biological targets. We now propose that an additional group of redox active molecules termed "reactive sulfur species" (RSS) are formed in vivo under conditions of oxidative stress. RSS are likely to include disulfide-S-oxides, sulfenic acids, and thiyl radicals, and are predicted to modulate the redox status of biological thiols and disulfides.
Asunto(s)
Radicales Libres/metabolismo , Estrés Oxidativo/fisiología , Azufre/metabolismo , Disulfuros/metabolismo , Glutatión/metabolismo , Metalotioneína/metabolismo , Modelos Químicos , Oxidación-Reducción , Ácidos Sulfénicos/metabolismo , Zinc/metabolismoRESUMEN
Synthesis and characterisation of organochalcogens has demonstrated a high correlation between their electrochemical oxidation potential on the glassy carbon electrode, their activity in bioassays and an unprecedented antioxidant activity in neuronal cell culture (EC50 approximately 20 nM) making electrochemical methodology a valuable tool in drug design for Alzheimer's and related diseases.