An Update on Thiol Signaling: S-Nitrosothiols, Hydrogen Sulfide and a Putative Role for Thionitrous Acid

Abstract

Long considered vital to antioxidant defenses, thiol chemistry has more recently been recognized to be of fundamental importance to cell signaling. S-nitrosothiols—such as S-nitrosoglutathione (GSNO)—and hydrogen sulfide (H2S) are physiologic signaling thiols that are regulated enzymatically. Current evidence suggests that they modify target protein function primarily through post-translational modifications. GSNO is made by NOS and other metalloproteins; H2S by metabolism of cysteine, homocysteine and cystathionine precursors. GSNO generally acts independently of NO generation and has a variety of gene regulatory, immune modulator, vascular, respiratory and neuronal effects. Some of this physiology is shared with H2S, though the mechanisms differ. Recent evidence also suggests that molecules resulting from reactions between GSNO and H2S, such as thionitrous acid (HSNO), could also have a role in physiology. Taken together, these data suggest important new potential targets for thiol-based drug development.

H2S- and NO-releasing gasotransmitter platform: A crosstalk signaling pathway in the treatment of acute kidney injury

“…Thus, small RSNOs such as GSNO may transfer the NO group from one thiol to another (S—NO → protein thiols), leading to S-nitrosated proteins, which is a mechanism dependent on the cell’s surrounding chemical environment [ 93 ]. GSNO is an endogenous molecule that increases NO bioavailability and has NO-like activity, such as vasodilation [ 94 ], anti-oxidant effects [ 95 ], tissue repair [ 96 , 97 ], anti-microbial activity [ 98 , 99 ], among others. GSNO (50 μg/kg body weight) has shown renoprotective effects on the treatment of sepsis-induced AKI applied to rat models with lipopolysaccharide-induced sepsis [ 100 ].…”

“…Finally, NO and H 2 S interaction might also affect each other synthesizing enzymes affecting their generation [ 134 ]. For more detailed discussion and mechanisms regarding the convergence of NO and H 2 S in biological system, we recommend important review articles in this topic [ 25 , 95 , 133 , 134 ].…”

Monitoring the Redox Status in Multiple Sclerosis

“…Hydroxyl radicals (OH • ) may also initiate the conversion of amino acids to peroxyl radicals [ 92 ]. Another reaction catalyzed by XO is the decomposition of S-nitrosothiols (RSNO), a RNS, to nitric oxide (NO), which reacts with a superoxide (O 2 −• ) anion to form peroxynitrite (ONOO − ) under aerobic conditions [ 137 ]. Hydropersulfide (RSSH) is a nucleophile, as well as electrophilic molecule that is readily reduced to extremely potent reductant thiol (RSH).…”

Monitoring the Redox Status in Multiple Sclerosis

“…Hydroxyl radicals (OH • ) may also initiate the conversion of amino acids to peroxyl radicals [42]. Another reaction catalyzed by XO is the decomposition of S-nitrosothiols (RSNO), a reactive nitrogen species, to nitric oxide (NO), which reacts with a superoxide (O2 −• ) anion to form peroxynitrite (ONOO − ) under aerobic conditions [94]. Hydropersulfide (RSSH) is a nucleophile as well as electrophilic molecule that is readily reduced to extremely potent reductant thiol (RSH).…”