A Source of Hydrogen Sulfide and a Mechanism of Its Release in the Brain

Abstract

Hydrogen sulfide (H2S) is recognized as a neuromodulator as well as neuroprotectant in the brain. H2S can be produced from cysteine by enzymes such as cystathionine beta-synthase. However, a mechanism for releasing H2S under physiologic conditions has not been identified. Here we show that H2S is released from bound sulfur, an intracellular store of sulfur, in neurons and astrocytes of mice and rats in the presence of physiologic concentrations of endogenous reducing substances glutathione and cysteine. The highest pH to release H2S from another sulfur store, acid-labile sulfur, which is localized mainly in mitochondria, is 5.4. Because mitochondria are not in the acidic condition, acid-labile sulfur may not be a physiologic source of H2S. Free H2S is immediately absorbed and stored as bound sulfur. Our novel method, using silver particles to measure free H2S, shows that free H2S is maintained at a low level in basal conditions. Alkalinization of the cytoplasm is required for effective release of H2S from bound sulfur, and this condition is achieved in astrocytes by the high concentrations of extracellular K+ that are normally present when nearby neurons are excited. These data present a new perspective on the regulation of H2S in the brain.

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

“…Following release, hydrogen sulfide can be stored in cells as bound sulfane sulfur that can be released by reducing conditions (44). Bound sulfane sulfur is the major determinant of physiological functions of hydrogen sulfide (45)(46)(47). Recent studies indicate that hydrogen sulfide has diverse effects on cell function including cell survival, hemodynamics, and inflammation (44); however, its role in protein synthesis has not been examined in detail.…”

The Mercaptopyruvate Sulfurtransferase of Trichomonas vaginalis Links Cysteine Catabolism to the Production of Thioredoxin Persulfide

“…Overexpression of MST in HEK 293-F cells resulted in an increase in the level of "bound" sulfane sulfur (50), possibly in the form of protein-bound cysteine persulfide. This is a storage form of sulfur that releases hydrogen sulfide when the intracellular conditions become more reducing (51). Persulfide sulfur is the likely source of sulfide for many biosynthetic pathways in vivo, including cofactor biosynthesis, ironsulfur cluster biosynthesis, lipoic acid biosynthesis, and tRNA sulfuration (23-26, 32, 52).…”

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

“…Circulating and intracellular S-nitrosothiols, which are formed by the interaction of NO with thiol (SH) groups, act as an important bioreservoir for NO [2]. Similarly, H2S can be stored in the form of sulfane sulfur and transported and released in response to a physiological stimulus [3]. A number of publications reported on the molecular interaction between H2S and NO or NO-donors [4][5][6][7][8][9][10][11][12][13][14], and H2S and NO were found to cooperatively regulate vascular tone by activating a neuroendocrine signaling pathway in which formation of nitroxyl (HNO) appears to play an important role [13].…”