tailieunhanh - Báo cáo khoa học: Oxidative stress induces a reversible flux of cysteine from tissues to blood in vivo in the rat

Glutathione (GSH) plays a key role in defense against oxidative stress. The availability of GSH is ensured in tissues by systems devoted to its mainte-nance in the reduced state and by the flux of GSH and cysteine between sites of biosynthesis and sites of utilization. Little is known about the effect of oxidative stress on the distribution of low-molecular-mass thiols and their exchange rate between tissues. | Oxidative stress induces a reversible flux of cysteine from tissues to blood in vivo in the rat Daniela Giustarini1 Isabella Dalle-Donne2 Aldo Milzani2 and Ranieri Rossi1 1 Department of Evolutionary Biology Laboratory of Pharmacology and Toxicology University of Siena Italy 2 Department of Biology University of Milan Italy Keywords cysteine diamide glutathione oxidative stress thiols Correspondence R. Rossi Department of Evolutionary Biology Laboratory of Pharmacology and Toxicology University of Siena via A. Moro 4 I-53100 Siena Italy Fax 39 577 234476 Tel 39 577 234198 E-mail ranieri@ Received 11 May 2009 revised 30 June 2009 accepted 3 July 2009 Glutathione GSH plays a key role in defense against oxidative stress. The availability of GSH is ensured in tissues by systems devoted to its maintenance in the reduced state and by the flux of GSH and cysteine between sites of biosynthesis and sites of utilization. Little is known about the effect of oxidative stress on the distribution of low-molecular-mass thiols and their exchange rate between tissues. In this study we found that a slow infusion of diamide a specific thiol-oxidizing compound evoked a dramatic increase in blood cysteine in rats. Our data suggest that inter-organ exchange of cysteine occurs that cysteine derives from both glutathione via y-glutamyl transpeptidase and methionine via homocysteine and the transsulfuration pathway and that these pathways are considerably influenced by oxidative stress. doi Introduction Cysteine Cys and glutathione GSH are the most abundant low-molecular-mass thiols LMM-SH with GSH predominating intracellularly and cysteine predominating in extracellular fluids 1 2 . These two compounds are metabolically inter-related and GSH in particular determines the redox state and represents a defense against damage mediated by reactive oxygen species ROS or reactive nitrogen species. Low GSH concentrations and a ratio of high glutathione .