Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Abstract

Significance: Accumulating evidence shows that hydrogen sulfide may function as a signaling molecule in processes such as neuromodulation in the brain and smooth muscle relaxation in the vascular system. It also has a cytoprotective effect, since it can protect neurons and cardiac muscle from oxidative stress and ischemiareperfusion injury, respectively. Hydrogen sulfide can also modulate inflammation, insulin release, and angiogenesis. Recent Advances: The regulation of the activity of 3-mercaptopyruvate sulfur transferase (3MST) along with cysteine aminotransferase (CAT), one of the H 2 S producing pathways, has been demonstrated. The production of H 2 S by the pathway, which is regulated by Ca 2+ and facilitated by thioredoxin and dihydrolipoic acid, is also involved in H 2 S signaling as well as cytoprotection. Sulfur hydration of proteins by H 2 S has been proposed to modulate protein functions. H 2 S-sensitive fluorescent probes, which enable us to measure the localization of H 2 S in real time, have been developed. Critical Issues: The basal concentrations of H 2 S have recently been measured and found to be much lower than those initially reported. However, the concentration of H 2 S reached in stimulated cells, as well as the regulation of H 2 S producing enzymes is not well understood. It has been proposed that some of the effects of H 2 S on the regulation of enzymes and receptors might be explained through the properties of sulfane sulfur (S 0 ), another form of active sulfur. Future Directions: The determination of H 2 S concentrations in activated cells using new methods including H 2 S-sensitive fluorescent probes, as well as the investigation of the effects of H 2 S using specific inhibitors, may provide better understanding of the physiological function of this molecule. Clarifying mechanisms of H 2 S activity may also facilitate the development of new therapeutic compounds. Antioxid. Redox Signal. 17, 45-57.

Vitamin D Up-regulates Glucose Transporter 4 (GLUT4) Translocation and Glucose Utilization Mediated by Cystathionine-γ-lyase (CSE) Activation and H2S Formation in 3T3L1 Adipocytes

“…Exogenous H 2 S supplementation reduces blood pressure, decreases atherosclerotic plaque size compared with those of controls in apolipoprotein E knock-out mice, and prevents progression of diabetic nephropathy in spontaneously hypertensive rats and endothelial dysfunction in diabetic rats (22,23). Several studies demonstrate that H 2 S is an antioxidant that regenerates GSH and lowers oxidative stress (5)(6)(7)11). Our recent study reported that supplementation with H 2 S increases glucose utilization and decreases secretion of the proinflammatory biomarkers IL-8 and MCP-1 in adipocyte and monocyte cell models (11,19).…”

Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway

“…Therefore, it is logical to speculate that inhibiting Hcy-induced ER stress may be a novel therapeutic strategy to prevent and ameliorate AD progression. Hydrogen sulfide (H 2 S), the third gaseous mediator, has recently been recognized as an important endogenous neuromodulator and neuroprotectant [26][27][28][29] . The most recent in vitro studies by our group have demonstrated that Hcy-associated neurotoxicity to PC12 cells is due to reduced endogenous generation of H 2 S [30] and that supplementation of sodium hydrosulfide (NaHS), the H 2 S-donor, ameliorates the Hcy elicited-neurotoxicity in PC12 cells [31] .…”

Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9

“…Physiologically, H 2 S is produced by three enzymes, namely cystathionine-␤-synthase (CBS), cystathionine-␥-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) (18). With few exceptions, the enzymatic pathways for H 2 S production are tissue specific.…”

“…For example, CBS is the main H 2 S-generating enzyme in the nervous system (16), CSE in the vascular system (43). On the other hand, 3MST is primarily located in the mitochondria (18). Interestingly, all the three enzymes are present in the kidney (17).…”