Disease relevance of H2-S

• These data also highlight the existence of 'crosstalk' between NO and H2S in this model of endotoxic shock [1].
• E. coli lipopolysaccharide (LPS) administration produced a dose (10 and 20 mg/kg ip)- and time (6 and 24 h)-dependent increase in plasma H2S concentration [2].
• Our results confirm that the rodent nose, and less so the lung, are highly sensitive to H2S-induced toxicity, with 10 ppm representing the NOAEL for ONL following subchronic inhalation [3].
• A 100% incidence of rhinitis was found in the male and female B6C3F1 mice exposed to 80 ppm H2S [3].
• Male Fischer-344 rats, female Sprague-Dawley rats, and female B6C3F1 mice exposed to 80 ppm H2S had depressed terminal body weights when compared with air-exposed controls [3].

High impact information on H2-S

• In contrast, castration of male mice decreases the levels of testosterone, SAM and H2S in the brain [4].
• Hydrogen sulfide (H2S) is endogenously produced in the brain from L-cysteine by the enzyme cystathionine beta-synthase (CBS) and functions as a neuromodulator in the brain [4].
• H2S selectively enhances NMDA receptor-mediated responses and alters hippocampal long-term potentiation (LTP) [4].
• In addition to this fast regulation, we describe here a slower form of the regulation of H2S production by testosterone and S-adenosyl-L-methionine (SAM), a CBS activator [4].
• The biosynthesis of both nitric oxide (NO) and hydrogen sulfide (H2S) is increased in lipopolysaccharide (LPS)-injected mice and rats but their interaction in these models is not known [1].

Chemical compound and disease context of H2-S

• The goal of this study was to characterize the toxicity of hydrogen sulfide (H2S), including nasal and pulmonary effects, in adult male and female Fischer-344 and Sprague-Dawley rats and B6C3F1 mice [3].
• Patch clamp studies of neuroblastoma cells have shown that in the presence of sodium hydrogen sulfide (NaHS; the in vitro precursor of H2S), addition of the sulfonated amino acids, taurine or cysteic acid resulted in reversible abolition of the inward sodium currents [5].
• It did not need supplementary CO2 for growth, produced H2S and was inhibited by brucella dyes and partially by i-erythritol [6].

Biological context of H2-S

• Subchronic H2S inhalation did not result in toxicologically relevant alterations in hematological indices, serum chemistries, or gross pathology [3].
• In contrast, co-treatment of cells with physiological concentrations of H2S (0.1-1 mmol/L) prevented PEITC mediated apoptosis as assessed using the parameters described [7].
• These data demonstrate histone H2S to be a unique histone associated with spermatogenesis in the mouse [8].
• Whilst H2S has been reported to relax precontracted rat arteries in vitro and to lower blood pressure in the rat, its effect in an inflammatory condition such as acute pancreatitis has not previously been reported [9].

Anatomical context of H2-S

• Polyacrylamide gel electrophoresis of products formed in a reticulocyte lysate-dependent cell-free translation system has enabled identification of histone variants, H1t, H2S, H2A . X, an H4-like protein and a low Mr protein (presumably TP and/or protamine) [10].
• A chromosomal histone, H2S, specific to the mouse testis has been purified [8].
• However, H2S generation and concentrations were greatest in the cecum and colon [11].
• A sulfate reduction assay demonstrated in situ production of H2S throughout the GI tract, confirming the presence of SRB [11].
• In this study, the effects of short-term (7 day) and long-term (1 year) inorganic sulfate supplementation of the drinking water on gastrointestinal (GI) sulfate and H2S concentrations (and thus activity of resident SRBs), and the density of large intestinal sulfomucin-containing goblet cells, were examined in C3H/HeJBir mice [11].

Associations of H2-S with chemical compounds

• These results show for the first time that nitroflurbiprofen downregulates the biosynthesis of proinflammatory H2S and suggest that such an effect may contribute to the augmented anti-inflammatory activity of this compound [1].
• In this study we examined the effect of the NO donor, nitroflurbiprofen (and the parent molecule flurbiprofen) on NO and H2S metabolism in tissues from LPS-pretreated rats [1].
• The H-2 S region genes C4 (fourth complement component) and Slp (sex-limited protein) are highly homologous [12].
• LPS (10 mg/kg ip, 6 h) increased plasma H2S concentration from 34.1 +/- 0.7 microM to 40.9 +/- 0.6 microM (n=6, P<0.05) while H2S formation from added L-cysteine was increased in both liver and kidney [2].
• These observations suggest that testosterone can regulate the brain H2S level via changing the level of SAM [4].

References