title: Carbamoylation abrogates the antioxidant potential of hydrogen sulfide.
abstract: Hydrogen sulfide (H2S) has been identified as the third gasotransmitter. Beside its role as signaling molecule in the cardiovascular and nervous system the antioxidant and cyto-protective properties of H2S have gained much attention. In the present study we show that cyanate, an uremic toxin which is found in abundant concentration in sera of patients suffering from chronic kidney disease (CKD), can abrogate the antioxidant and cytoprotective activity of H2S via S-carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H2S. Carbamoylation strongly inhibited the free radical scavenging (ABTS(+·) and alkylperoxyl ROO(·)) properties of H2S. The extent of intracellular ROS formation induced by ROO(·) was diminished by H2S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H2S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H2S but carbamoylation significantly reduced the effect. Thus, S-carbamoylation of low molecular weight thiols by abrogating their antioxidant potential may contribute to the higher oxidative stress observed in CKD.
authors.affiliation: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Waehringerstr. 10, 1090 Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Praschberger
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
authors.forename: Christian
authors.initials: C
authors.lastname: Laggner
authors.forename: Leopold
authors.initials: L
authors.lastname: Jirovetz
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kapiotis
authors.forename: Bernhard M K
authors.initials: BM
authors.lastname: Gmeiner
authors.forename: Hilde
authors.initials: H
authors.lastname: Laggner
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D003485:Cyanates / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D016166:Free Radical Scavengers / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D003485:Cyanates; D016166:Free Radical Scavengers; C006894:S-carbamylcysteine; D003545:Cysteine; C005057:isocyanic acid; D006862:Hydrogen Sulfide
keywords: (3,3′,5,5′-tetramethylbenzidine); 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt; 2,2′-azobis(2-amidinopropane) hydrochloride; 2′,7′-dichlorofluorescein; AAPH; ABTS; Antioxidant; Chronic kidney disease; Cyanate; DCF; Hydrogen sulfide; Isocyanic acid; S-Carbamoylation; TMB