Hydrogen Sulfide: A Novel Player in Airway Development, Pathophysiology of Respiratory Diseases, and Antiviral Defenses

Abstract

Hydrogen sulfide (HS) is a biologically relevant signaling molecule in mammals. Along with the volatile substances nitric oxide (NO) and carbon monoxide (CO), HS is defined as a gasotransmitter. It plays a physiological role in a variety of functions, including synaptic transmission, vascular tone, angiogenesis, inflammation, and cellular signaling. The generation of HS is catalyzed by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST). The expression of CBS and CSE is tissue specific, with CBS being expressed predominantly in the brain, and CSE in peripheral tissues, including lungs. CSE expression and activity are developmentally regulated, and recent studies suggest that CSE plays an important role in lung alveolarization during fetal development. In the respiratory tract, endogenous HS has been shown to participate in the regulation of important functions such as airway tone, pulmonary circulation, cell proliferation or apoptosis, fibrosis, oxidative stress, and inflammation. In the past few years, changes in the generation of HS have been linked to the pathogenesis of a variety of acute and chronic inflammatory lung diseases, including asthma and chronic obstructive pulmonary disease. Recently, our laboratory made the critical discovery that cellular HS exerts broad-spectrum antiviral activity both in vitro and in vivo, in addition to independent antiinflammatory activity. These findings have important implications for the development of novel therapeutic strategies for viral respiratory infections, as well as other inflammatory lung diseases, especially in light of recent significant efforts to generate controlled-release HS donors for clinical therapeutic applications.

Exercise training ameliorates bleomycin‐induced epithelial mesenchymal transition and lung fibrosis through restoration of H2S synthesis

“…Endogenous H 2 S in lung tissues is mainly produced by CBS and CSE with L‐cysteine used as a main substrate . As shown in Figure A, bleomycin treatment resulted in significant decreases in protein expressions of both CBS and CSE in the lung.…”

“…Endogenous H 2 S in mammal organs can be mainly produced by cysteine‐β‐synthetase (CBS) and cysteine‐γ‐lyase (CSE) with L‐cysteine used as a main substrate. The expression of both CBS and CSE has been detected in lung tissues . There is now accumulating evidence that endogenous H 2 S plays vital roles in the pathogenesis of a variety of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases .…”

<p>A Novel Liposomal S-Propargyl-Cysteine: A Sustained Release of Hydrogen Sulfide Reducing Myocardial Fibrosis via TGF-β1/Smad Pathway</p>

“…Over the last decade, great strides have been made in our understanding of the biological and physiological significance of hydrogen sulfide gas (H 2 S) in mammals. [1][2][3] Importantly, this molecule is regarded as the third gasotransmitter alongside carbon monoxide and nitric oxide. In the cells and tissues of our bodies, H 2 S is produced by the enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase (3-MST).…”

Marvel analysis of the measured high-resolution rovibrational spectra of H232S

“…On earth, microbial respiration of seawater sulfate creates a hydrogen sulfide-rich ecosystem [5], suggesting that H 2 S is a component for a potential microbial life sustaining atmosphere on Venus [2], and a potential biomarker for life on exoplanets [6]. H 2 S influences many physiological processes [7], it is of importance in the treatment of respiratory diseases [8], and it is used as a measure of the quality of air near oil refineries [9]. The parent isotopologue, H 2 32 S, was first detected in interstellar space in 1972 [10].…”