References

The chemical versatility of sulfur and its abundance in the prebiotic Earth as reduced sulfide (H2S) implicate this molecule in the origin of life 3.8 billion years ago and also as a major source of energy in the first seven-eighths of evolution. This article provides an in-depth review of the origins of hydrogen sulfide’s physiological functions, also explaining its unique role as a signalling molecule and metabolic regulator, including its anti-inflammatory properties.

Hydrogen sulfide (H2S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H2S (stimulation of angiogenesis, relaxation of vascular smooth muscle) resemble those of nitric oxide (NO). Although it was generally assumed that H2S and NO exert their effects via separate pathways, the results of the current study show that H2S and NO are mutually required to elicit angiogenesis and vasodilatation.

Hydrogen sulfide (H2S) is a gaseous mediator synthesized from cysteine by cystathionine γ lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H2S donors and genetic experiments using CSE knockout mice suggest important roles for this vasodilator gas in the regulation of blood vessel caliber, cardiac response to ischemia/reperfusion injury, and inflammation.

In vascular tissues, hydrogen sulphide (H2S) is mainly produced from L-cysteine by the cystathionine gamma-lyase (CSE) enzyme. Recent studies show that administration of H2S to endothelial cells in culture stimulates cell proliferation, migration and tube formation. Angiogenesis, the formation of new blood vessels, is crucial in the early stage of wound healing. Pharmacological modulation of H2S-mediated angiogenic pathways may open the door for novel therapeutic approaches.

The recent discovery that hydrogen sulfide (H2S) is an endogenously produced gaseous second messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential of H2S as a cardioprotective agent. In the current study, we demonstrate that H2S may be of value in cytoprotection during the evolution of myocardial infarction and that either administration of H2S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.

H2S is an important gasotransmitter, generated in mammalian cells from L-cysteine metabolism. As it stimulates KATP channels in vascular smooth muscle cells, H2S may also function as an endogenous opener of KATP channels in INS-1E cells, an insulin-secreting cell line. Interaction among H2S, glucose and the KATP channel may constitute an important and novel mechanism for the fine control of insulin secretion from pancreatic β-cells.

The endogenous metabolism and physiological functions of hydrogen sulfide (H2S) position this gas well in the novel family of endogenous gaseous transmitters, termed “gasotransmitters.” This positioning of H2S will open an exciting field—H2S physiology—encompassing realization of the interaction of H2S and other gasotransmitters, sulfurating modification of proteins, and the functional role of H2S in multiple systems. It may shed light on the pathogenesis of many diseases related to the abnormal metabolism of H2S.

An abundance of experimental evidence suggests that hydrogen sulfide (H2S) plays a prominent role in physiology and pathophysiology. Many targets exist for H2S therapy. The molecular targets of H2S include proteins, enzymes, transcription factors, and membrane ion channels. Novel H2S precursors are being synthesized and discovered that are capable of releasing H2S in a slow and sustained manner. This presents a novel and advantageous approach to H2S therapy for treatment of chronic conditions associated with a decline in endogenous H2S, such as diabetes and cardiovascular disease.