Interaction of Hydrogen Sulfide with Oxygen Sensing under Hypoxia

Based on the discovery of endogenous H2S production, many in depth studies show this gasotransmitter with a variety of physiological and pathological functions. Three enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST), are involved in enzymatic production of H2S. Emerging evidence has elucidated an important protective role of H2S in hypoxic conditions in many mammalian systems. However, the mechanisms by which H2S senses and responses to hypoxia are largely elusive. Hypoxia-inducible factors (HIFs) function as key regulators of oxygen sensing, activating target genes expression under hypoxia. Recent studies have shown that exogenous H2S regulates HIF action in different patterns. The activation of carotid bodies is a sensitive and prompt response to hypoxia, rapidly enhancing general O2 supply. H2S has been identified as an excitatory mediator of hypoxic sensing in the carotid bodies. This paper presents a brief review of the roles of these two pathways which contribute to hypoxic sensing of H2S.