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.
Highlights
Since the first description of hydrogen sulfide (H2 S) as a toxic gas in 1713 by Bernardino
We discovered that hydrogen polysulfides (H2 Sn, n ≥ 2) are potential signaling molecules produced by 3-mercaptopyruvate sulfurtransferase (3MST)
Patients that recover from H2 S poisoning show cognitive decline, and the levels of neurontransmitters in the brains of animals exposed to H2 S change, suggesting that the brain is vulnerable to H2 S toxicity [1]
Summary
Patients that recover from H2 S poisoning show cognitive decline, and the levels of neurontransmitters in the brains of animals exposed to H2 S change, suggesting that the brain is vulnerable to H2 S toxicity [1]. The observations that H2 S is produced by enzymes and exists in the brain prompted us to study a physiological role of this molecule. The activities of CBS and CSE have been intensively studied in the liver and kidney, but little is known about them in the brain. H2 S with one-tenth of the concentration of DTT exerted a greater effect than that of DTT [5] This observation suggested that there is an additional mechanism for LTP induction by H2 S. We found that H2 S induces Ca2+ influx in astrocytes, which was greatly suppressed by La3+ , Gd3+ , and ruthenium red, broad-spectrum inhibitors known for transient receptor potential (TRP) channels, suggesting that H2 S activates TRP channels [13]. H2 S was reported to activate TRPA1 channels in urinary bladder and in sensory neurons, but concentrations greater than 1 mM were required for inducing responses [14,15]
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