Hydrogen Sulfide (H2S) and Polysulfide (H2Sn) Signaling: The First 25 Years

Abstract

Since the first description of hydrogen sulfide (H2S) as a toxic gas in 1713 by Bernardino Ramazzini, most studies on H2S have concentrated on its toxicity. In 1989, Warenycia et al. demonstrated the existence of endogenous H2S in the brain, suggesting that H2S may have physiological roles. In 1996, we demonstrated that hydrogen sulfide (H2S) is a potential signaling molecule, which can be produced by cystathionine β-synthase (CBS) to modify neurotransmission in the brain. Subsequently, we showed that H2S relaxes vascular smooth muscle in synergy with nitric oxide (NO) and that cystathionine γ-lyase (CSE) is another producing enzyme. This study also opened up a new research area of a crosstalk between H2S and NO. The cytoprotective effect, anti-inflammatory activity, energy formation, and oxygen sensing by H2S have been subsequently demonstrated. Two additional pathways for the production of H2S with 3-mercaptopyruvate sulfurtransferase (3MST) from l- and d-cysteine have been identified. We also discovered that hydrogen polysulfides (H2Sn, n ≥ 2) are potential signaling molecules produced by 3MST. H2Sn regulate the activity of ion channels and enzymes, as well as even the growth of tumors. S-Sulfuration (S-sulfhydration) proposed by Snyder is the main mechanism for H2S/H2Sn underlying regulation of the activity of target proteins. This mini review focuses on the key findings on H2S/H2Sn signaling during the first 25 years.

The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice

“…Hydrogen sulfide (H 2 S) was considered to be an environmental toxin before it was identified as an endogenously produced mediator in the 1940s (for a review, see [ 1 ]). At present, H 2 S is recognized as an important gasotransmitter, which plays roles in a wide spectrum of physiological processes in the brain as well as in peripheral tissues in health and disease [ 2 , 3 ]. H 2 S is synthesized both centrally and peripherally by specific enzymes including cystathionine β -synthase, cystathionine γ -lyase, and 3-mercaptopyruvate sulfurtransferase, but alternative H 2 S-producing pathways are also known [ 3 , 4 ].…”

“…At present, H 2 S is recognized as an important gasotransmitter, which plays roles in a wide spectrum of physiological processes in the brain as well as in peripheral tissues in health and disease [ 2 , 3 ]. H 2 S is synthesized both centrally and peripherally by specific enzymes including cystathionine β -synthase, cystathionine γ -lyase, and 3-mercaptopyruvate sulfurtransferase, but alternative H 2 S-producing pathways are also known [ 3 , 4 ]. Endogenously, H 2 S is present within the nM to low µM concentration range and it is catabolized by enzymatic and non-enzymatic processes [ 5 ].…”

“…Endogenously, H 2 S is present within the nM to low µM concentration range and it is catabolized by enzymatic and non-enzymatic processes [ 5 ]. In the past decades, the role of H 2 S has been implicated in a number of physiological and pathological conditions [ 2 , 3 , 4 ], including the regulation of core body temperature ( T b ) [ 6 ].…”

“…However, injection of low doses of sodium sulfide (Na 2 S), i.e., an H 2 S-releasing salt, into the lateral ventricle or the medullary raphe did not cause any significant effect on T b of euthermic rats [ 19 , 21 ]. With regards to the thermoeffector mechanism, although it is well known that H 2 S plays a role in the regulation of the vascular tone [ 3 , 6 ], it is unknown whether skin vasodilation, a principal autonomic heat-dissipating thermoeffector [ 22 ], is recruited in the H 2 S-induced hypothermia. A plausible molecular target for a thermoregulatory effect could be a sensor that is expressed on neurons located within the thermoeffector pathways, therefore its stimulation can directly lead to a change in deep T b via modulation of the activity of one or more thermoeffector organs.…”

Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules

“…Hydrogen sulfide (H 2 S) was shown to be a neuromodulator in the brain in 1996 [ 1 ], and since then, many biological studies have established that H 2 S is an endogenously produced gasotransmitter that is involved in multiple physiological processes, including cytoprotection against oxidative stress, mediation of neurotransmission, and regulation of inflammation [ 2 ]. In addition to H 2 S, reactive sulfur species produced by oxidation of H 2 S, including sulfane sulfur-containing molecules, play key roles in various biological processes [ 3 , 4 , 5 ]. Sulfane sulfur, often represented as S 0 , has an apparent oxidation state of zero, at least in one of its tautomeric forms, and is bonded to other sulfur atom(s) [ 6 , 7 , 8 , 9 ].…”