Abstract
Hydrogen sulfide (H2S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems and immune response. Three enzymes mediate the endogenous production of H2S: cystathione β-synthase (CBS), cystathione γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). CBS and CSE localizations are organ-specific. 3-MST is a mitochondrial and cytosolic enzyme. The generation of H2S is firmly regulated by these enzymes under normal physiological conditions. Recent studies have highlighted the role of H2S in cellular redox homeostasis, as it displays significant antioxidant properties. H2S exerts antioxidant effects through several mechanisms, such as quenching reactive oxygen species (ROS) and reactive nitrogen species (RNS), by modulating cellular levels of glutathione (GSH) and thioredoxin (Trx-1) or increasing expression of antioxidant enzymes (AOE), by activating the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2). H2S also influences the activity of the histone deacetylase protein family of sirtuins, which plays an important role in inhibiting oxidative stress in cardiomyocytes and during the aging process by modulating AOE gene expression. This review focuses on the role of H2S in NRF2 and sirtuin signaling pathways as they are related to cellular redox homeostasis.
Highlights
Hydrogen sulfide (H2 S) is an inorganic and colorless gas, with strong odor and toxic effects at high concentrations [1]
Whenever a change in redox status occurs by increased cellular reactive oxygen species (ROS) levels, Kelch-like ECH-associated protein 1 (Keap1) dimer changes conformation due to the breaking of disulfide bonds between cysteine residues, and releases nuclear factor (erythroid-derived 2)-like 2 (NRF2), which translocates to the nucleus and induces the transcription of antioxidant enzymes (AOE) genes to attain redox homestastis [23]
An increased number of studies have confirmed the beneficial use of H2 S donors in neuronal, cardiovascular and other oxidative stress-dependent diseases [3,4]
Summary
Hydrogen sulfide (H2 S) is an inorganic and colorless gas, with strong odor and toxic effects at high concentrations [1]. In the last few years, H2 S has been identified as the third most physiologically important gasotransmitter participating in multiple cellular signaling pathways, along with carbon monoxide (CO) and nitric oxide (NO) [2] It plays a physiological role in a variety of cellular and organ functions and a protective role in multiple pathological conditions, displaying vasoactive, cytoprotective, anti-inflammatory and antioxidant activities (reviewed in [3]). Oxidation is the mostthrough commonthe reaction, and encompasses the intermediate molecule It takes place in the mitochondria sequential action of sulfide: rapid metabolism of to sulfate and sulfite species with thiosulfate as an intermediate molecule. Scavenging by dimethylsulfide metalloproteins and thiol S-methyltransferase mainly in theby cytoplasm, and reaction, it seems toproducing have a lesser role than involves the binding of H2S(TMST).
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