Gasping for Sulfide: A Critical Appraisal of Hydrogen Sulfide in Lung Disease and Accelerated Aging.

Hydrogen sulfide (HS) is a gaseous signaling molecule involved in a plethora of physiological and pathological processes. It is primarily synthesized by cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase as a metabolite of the transsulfuration pathway. HS has been shown to exert beneficial roles in lung disease acting as an anti-inflammatory and antiviral and to ameliorate cell metabolism and protect from oxidative stress. HS interacts with transcription factors, ion channels, and a multitude of proteins post-translational modifications through S-persulfidation ("sulfhydration"). Perturbation of endogenous HS synthesis and/or levels have been implicated in the development of accelerated lung aging and diseases, including asthma, chronic obstructive pulmonary disease, and fibrosis. Furthermore, evidence indicates that persulfidation is decreased with aging. Here, we review the use of HS as a biomarker of lung pathologies and discuss the potential of using HS-generating molecules and synthesis inhibitors to treat respiratory diseases. Furthermore, we provide a critical appraisal of methods of detection used to quantify HS concentration in biological samples and discuss the challenges of characterizing physiological and pathological levels. Considerations and caveats of using HS delivery molecules, the choice of generating molecules, and concentrations are also reviewed. . 35, 551-579.