Physiological roles of hydrogen sulfide in mammalian cells, tissues and organs

Abstract

H ₂S belongs to the class of molecules known as gasotransmitters, which also includes nitric oxide (NO) and carbon monoxide (CO). Three enzymes are recognized as endogenous sources of H ₂S in various cells and tissues: cystathionine g-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). The current article reviews the regulation of these enzymes as well as the pathways of their enzymatic and non-enzymatic degradation and elimination. The multiple interactions of H ₂S with other labile endogenous molecules (e.g. NO) and reactive oxygen species are also outlined. The various biological targets and signaling pathways are discussed, with special reference to H ₂S and oxidative posttranscriptional modification of proteins, the effect of H ₂S on channels and intracellular second messenger pathways, the regulation of gene transcription and translation and the regulation of cellular bioenergetics and metabolism. The pharmacological and molecular tools currently available to study H ₂S physiology are also reviewed, including their utility and limitations. In subsequent sections, the role of H ₂S in the regulation of various physiological and cellular functions is reviewed. The physiological role of H ₂S in various cell types and organ systems are overviewed. Finally, the role of H ₂S in the regulation of various organ functions is discussed as well as the characteristic bell-shaped biphasic effects of H ₂S. In addition, key pathophysiological aspects, debated areas, and future research and translational areas are identified A wide array of significant roles of H ₂S in the physiological regulation of all organ functions emerges from this review.