S-glutathionylation

Lange, R.W. et al., Intracellular S-glutathionyl adducts in murine lung and human bron-choepithelial cells after exposure to diisocyanatotoluene, Chem. Res. Toxicol., 12, 931, 1999. 

The main products obtained from the reaction between adreno-chrome (1) and glutathione have been shown to result from the 1,4-addition of glutathione to the C-5 unsaturated carbonyl systems in 1 involving the C6-C7 and the C4-C9 double bonds and are probably [Pg.288]

Abbreviations CDNB, l-chloro-2,4-dinitrobenzene GSH, glutathione GS-DNB, l-(S-glutathionyl)-2,4-dinitrobenzene GST, glutathione-S-transferase NBD-C1, 7-chloro-4-nitrobenzo-2-oxa-l,3-diazole EA, ethacrynic acid. 

Recent studies have shown increased glutathionylation of specific proteins in AD patients compared with control subjects [Newman et al., 2007], The exact function of this reversible oxidative modification is unknown. Further studies investigating the specific in vivo effects of. S -glutathionylation in oxidative stress are important to determining the role of S -glutathionylation in the AD brain and neurodegenerative disorders. 

Borges CR, Geddes T, Watson JT, Kuhn DM. 2002. Dopamine biosynthesis is regulated by S-glutathionylation. Potential mechanism of tyrosine hydroxylast inhibition during oxidative stress. J Biol Chem 277 48295 -8302. 

Giustarini D, Milzani A, Aldini G, Carini M, Rossi R, Dalle-Donne I. 2005. S-nitrosation versus S-glutathionylation of protein sulfhydryl groups by S-nitroso-glutathione. Antioxid Redox Signal 7 930-939. 

Giustarini D, Rossi R, Milzani A, Colombo R, Dalle-Donne 1.2004. S-glutathionylation From redox regulation of protein functions to human diseases. J Cell Mol Med 8 201-212. 

Johansson C, Lillig CH, Elolmgren A. 2004. Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. J Biol Chem 279 7537-7543. 

Newman SF, Sultana R, Perluigi M, Coccia R, Cai J, Pierce WM, Klein JB, Turner DM, Butterfield DA. 2007. An increase in S-glutathionylated proteins in the Alzheimer s disease inferior parietal lobule, a proteomics approach. J Neurosci Res 85 1506-1514. 

Shelton MD, Chock PB, Mieyal JJ. 2005. Glutaredoxin Role in reversible protein S-glutathionylation and regulation of redox signal transduction and protein translocation. Antioxid Redox Signal 7 348-366. 

Salgues, M., Cheynier, V., Gunata, Z., and Wylde, R. (1986). Oxidation of grape juice 2-S-glutathionyl caffeoyl tartaric acid by Botrytis cinerea laccase and characterization of a new substance 2,5-di-S-glutathionyl caffeoyl tartaric acid. J. Food Sci. 51,1191-1194. 

Figure 13.8. GST may enhance the toxicity of xenobiotics. Ethylene dibromide is a substrate of GST (theta and others) to be converted to l-bromo-2-.S -glutathionyl ethane, which facilitates spontaneous formation of the episulfonium ion. The episulfonium ion attacks the N7 position of guanine and causes DNA adduct formation. GST pi Ilel05 to Val polymorphism, causing increased GSTpi activity, appears to correlate with higher testicular and bladder cancer. This may also be involved in GSTpi-mediated activation of unidentified xenobiotics. (Adapted from Henderson et al. Proc. Natl. Acad. Sci. USA 95, 5275-5280,1998.)...

M21. Mohr, S., Hallak, H., de Boitte, A., Lapetina, E. G., and Brune, B., Nitric oxide-induced S-glutathionylation and inactivation of glyceraldehyde-3-phosphate dehydrogenase. J. Biol. Chem. 274, 9427-9430 (1999). 

Cheynier, V., Van Hulst, M. W. (1988). Oxidation of trans-caftaric acid and 2-S-glutathionyl caftaric acid in model solutions. J. Agric. Food Chem., 36, 10-15. 

S-glutathionyl)paracetamol Figure 2 Metabolism of paracetamol (acetaminophen). 

NO-induced protein S-glutathionylation was proposed for the first time in 1988 by J.W. Park as a possible mechanism for the inactivation of yeast alcohol dehydrogenase by NO [32]. However, it took almost 10 years until the possibility that NO might be able to direct the incorporation of GSH to protein sulfhydryls was reconsidered. In 1997. it could be demonstrated that micromolar concentrations of GSNO inhibit aldose reductase through site-specific mixed disulphide formation at a conserved cysteine residue in its catalytic site... 

One year later, a role of NO as mediator of protein thiolation in intact cells was highlighted by experiments demonstrating that endothelial cells respond to exogenous NO production with the transient S-thiolation of a number of as yet unidentified cellular proteins [34]. Similarly, S-nitrosocysteine was found to induce some S-glutathiolation in NIH-3T3 cells and rat hepatocytes. It is important to mention that other NO-derived species with a strong oxidative potential, such as peroxynitrite (ONOO-) are able to induce S-glutathionylation as is the case with the Ca-ATPase of sarcoplasmic reticulum which in vitro becomes inactivated [35]. 

I). Most redox-responsive transcriptional activators in mammalian cells are likely to be regulated by one of these modifications [45]. Among them, S-glutathionylation has emerged as a potential reaction by which the cells may transduce oxidative stress into repression of gene expression. 

Figure 2. The incubation in the presence of GSSG induces the S-glutathionylation of c-Jun and an inhibition in its DNA binding activity. A) The DNA binding of c-Jun was subjected to EMSA experiments in the presence of different GSH/GSSG ratios or DTT. B) In the figure is represented the amount of c-Jun protein which is modified to mixed disulfide with glutathione (P-S-S-G) or to other modifications.

---