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Chemical characterization of the smallest S-nitrosothiol, HSNO; cellular cross-talk of H2S and S-nitrosothiols.


ABSTRACT: Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H(2)S reacts with S-nitrosothiols to form thionitrous acid (HSNO), the smallest S-nitrosothiol. These results demonstrate that, at the cellular level, HSNO can be metabolized to afford NO(+), NO, and NO(-) species, all of which have distinct physiological consequences of their own. We further show that HSNO can freely diffuse through membranes, facilitating transnitrosation of proteins such as hemoglobin. The data presented in this study explain some of the physiological effects ascribed to H(2)S, but, more broadly, introduce a new signaling molecule, HSNO, and suggest that it may play a key role in cellular redox regulation.

SUBMITTER: Filipovic MR 

PROVIDER: S-EPMC3408084 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Chemical characterization of the smallest S-nitrosothiol, HSNO; cellular cross-talk of H2S and S-nitrosothiols.

Filipovic Milos R MR   Miljkovic Jan Lj JLj   Nauser Thomas T   Royzen Maksim M   Klos Katharina K   Shubina Tatyana T   Koppenol Willem H WH   Lippard Stephen J SJ   Ivanović-Burmazović Ivana I  

Journal of the American Chemical Society 20120717 29


Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H(2)S reacts with S-nitrosothiols to form thionitrous acid (HSNO), the smallest S-nitrosothiol. These results demonstrate that, at the cellular level, HSNO can be metabolized to afford NO(+), NO, and NO(-) species, all of which have di  ...[more]

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