Physiological roles of glutathione in organism

Abstract

Glutation (γ-glutamil-cisteinilglicin, GSH) je tripeptid prisutan u velikim količinama u svim stanicama sisavaca. Sintetizira se u stanicama svih organa, posebno u jetri. Najveća količina nalazi se u citosolu, mitohondriju i ER. Služi kao antioksidans i detoksifikator u mnogim procesima metabolizma i regulira stanična zbivanja. Postoji u dva oblika-reduciranom (GSH) koji može oksidirati do disulfida (GSSG), a njihov omjer određuje redoks stanje stanice koje je bitan posrednik u više procesa. U ovom radu obrađuju se uloge GSH kao regulatora staničnog redoks statusa u kontroli transkripcijskih faktora i imunološkog odgovora te kao kofaktora u sintezi proupalnih posrednika ili spoja s NO. Smanjenje razine GSH u uvjetima oksidacijskog stresa aktivira transkripcijske faktore NF-κB i AP-1 koji potiču ekspresiju mnogih proupalnih gena i gena za citokine. U imunološkom sustavu GSH ima dvojaku ulogu: utječe na smanjenje sinteze citokina koji mogu dodatno pojačati oksidacijski stres, a dovoljna količina GSH potrebna je za proliferaciju limfocita T i odgovarajući imunološki odgovor. GSH služi i kao kofaktor u pojedinim koracima sinteze proupalnih posrednika, leukotriena i prostaglandina, koje kataliziraju membranski enzimi porodice GSH S-transferaza imena MAPEG. NO se može spojiti s GSH pri čemu nastaje S-nitrozoglutation (GSNO) koji može posttranslacijskom modifikacijom preko S-tiolacije ili S-glutationilacije utjecati na aktivnost proteina i time inhibirati apoptozu ili utjecati na redoks stanje stanice.Glutathione (γ-glutamylcysteinylglycine, GSH) is a tripeptid present in large levels in all mammalian tissues. It is synthetized within the cells of all organs, especially in the liver. The largest levels of GSH are present in cytosol, mitochondria and ER. GSH serves as antioxidant, detoxifying agent in a number of metabolism processes and it modulates cell events. There are two forms of GSH: reduced form (GSH) which can oxidize to disulphide (GSSG), GSH/GSSG ratio determines redox state of cells which is important factor in many processes. This review explaines roles of GSH as a regulator of cellular processes in a modulation of transcriptional factors and immune responses and, also, as a cofactor in proinflammatory mediators synthesis and NO-adduct formation. In conditions of oxidative stress, a decrease in GSH levels activates transcriptional factors NF-κB i AP-1 which then activate pro-inflammatory genes and cytokine genes expression. GSH has a double role in the immune system: it affects the decrease in cytokine synthesis which can enhance oxidative stress and, also, adequate levels of GSH are essential for T lymphocyte proliferation and successful immune response. In the synthesis of pro-inflammatory mediators, leukotrienes and prostaglandins, GSH serves as a cofactor in some of the steps catalyzed by special GSH-S transferase membrane-bound enzymes called MAPEG. NO can form an adduct with GSH forming S-nitrosoglutathione (GSNO) which by posttranslational modification through Sthiolation and S-glutathionilation can modify protein activity and additionally apoptosis inhibition or cell redox state