Carbamoylation abrogates the antioxidant potential of hydrogen sulfide

Abstract Hydrogen sulfide (H 2 S) 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 H 2 S 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 H 2 S via S -carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H 2 S. Carbamoylation strongly inhibited the free radical scavenging (ABTS + and alkylperoxyl ROO ) properties of H 2 S. The extent of intracellular ROS formation induced by ROO was diminished by H 2 S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H 2 S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H 2 S 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.