Hydrogen sulfide: a gasotransmitter of clinical relevance

Abstract

Though the existence of H2S in biological tissues has been known for over 300 years, it is the most recently appreciated of the gasotransmitters as a physiologic messenger molecule. The enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) had long been speculated to generate H2S, and inhibitors of these enzymes had been employed to characterize influences of H2S in various organs. Definitive evidence that H2S is a physiologic regulator came with the development of mice with targeted deletion of CSE and CBS. Best characterized is the role of H2S, formed by CSE, as an endothelial derived relaxing factor that normally regulates blood pressure by acting through ATP-sensitive potassium channels. H2S participates in various phases of the inflammatory process, predominantly exerting anti-inflammatory actions. Currently, the most advanced efforts to develop therapeutic agents involve the combination of H2S donors with non-steroidal anti-inflammatory drugs (NSAIDs). The H2S moiety provides cytoprotection to gastric mucosa normally adversely affected by NSAIDs, while the combination of H2S and inhibition of prostaglandin synthesis may afford synergistic anti-inflammatory influences.

Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors

“…Thus H 2 S is believed to act as a pro-inflammatory mediator. However, the role of H 2 S in inflammatory reaction remains controversial, with anti-inflammatory effects having been documented (9,42,43,51). The controversy might be related to several factors such as the concentration, the duration of presence, and site of production (15,46).…”

Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137

“…Intracellular levels of H 2 S are reported to be decreased during ischaemia-reperfusion as a results of overwhelming ROS generation which limits H 2 S synthesis and increases its degradation (Vandiver and Snyder, 2012). GYY4137 elicited significant infarct limitation when administered prior to reperfusion.…”

Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells

“…Cysteine aminotransferase acts in concert with 3-mercaptopyruvate sulfurtransferase to release H 2 S from L-cysteine and ketoacids. The distribution of H 2 Ssynthesizing enzymes has a tissue-specific pattern: CBS is highly expressed in the brain and nervous systems, and CSE is the predominant enzyme in the vasculature and heart (Li et al 2011;Vandiver and Snyder 2012). Alternations to H 2 S metabolism lead to an array of pathologic disturbances in the form of hypertension, atherosclerosis, heart failure, diabetes, cirrhosis, sepsis, neurodegenerative disease, and asthma in animal models and humans (Li et al 2011).…”