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Hydrogen sulfide (H2S) has been recently recognized as an important gasotransmitter with cardioprotections, and iron is vital for various cellular activities. This study explored the regulatory role of H2S on iron metabolism and mitochondrial functions in cultured rat cardiac cells. Rotenone, a mitochondrial complex I inhibitor, was used for establishing an in vitro model of ischemic cell damage. It was first found that rotenone induced oxidative stress and lipid peroxidation and decreased mitochondrial membrane potential and ATP generation, eventually causing cell death. The supplement of H2S at a physiologically relevant concentration protected from rotenone-induced ferroptotic cell death by reducing oxidative stress and mitochondrial damage, maintaining GPx4 expression and intracellular iron level. Deferiprone, an iron chelator, would also protect from rotenone-induced ferroptosis. Further studies demonstrated that H2S inhibited ABCB8-mediated iron efflux from mitochondria to cytosol and promoted NFS1-mediated Fe-S cluster biogenesis. It is also found that rotenone stimulated iron-dependent H2S generation. These results indicate that H2S would protect cardiac cells from ischemic damage through preserving mitochondrial functions and intracellular Fe-S cluster homeostasis.

The organic sulfur-containing compounds glucosinolates (GSLs) and the novel gasotransmitter H2S are known to have cardioprotective effects. This study investigated the antioxidant effects and H2S-releasing potential of three GSLs ((3E)-4-(methylsulfanyl)but-3-enyl GSL or glucoraphasatin, 4-hydroxybenzyl GSL or glucosinalbin, and (RS)-6-(methylsulfinyl)hexyl GSL or glucohesperin) in rat cardiac cells. It was found that all three GSLs had no effect on cardiac cell viability but were able to protect against H2O2-induced oxidative stress and cell death. NaHS, a H2S donor, also protected the cells from H2O2-stimulated oxidative stress and cell death. The GSLs alone or mixed with cysteine, N-acetylcysteine, glutathione, H2O2, iron and pyridoxal-5′-phosphate, or mouse liver lysates did not induce H2S release. The addition of GSLs also did not alter endogenous H2S levels in cardiac cells. H2O2 significantly induced cysteine oxidation in the cystathionine gamma-lyase (CSE) protein and inhibited the H2S production rate. In conclusion, this study found that the three tested GSLs protect cardiomyocytes from oxidative stress and cell death but independently of H2S signaling.

The role of endogenous hydrogen sulfide (H2S) as an antioxidant regulator has sparked interest in its function within inflammatory diseases. Cigarette and alcohol use are major causes of premature death, resulting from chronic oxidative stress and subsequent tissue damage. The activation of the Nrf2 antioxidant response by H2S suggests that this novel gasotransmitter may function to prevent or potentially reverse disease progression caused by cigarette smoking or alcohol use. The purpose of this study is to review the interrelationship between H2S signaling and cigarette smoking or alcohol drinking. Based on the databases of cellular, animal, and clinical studies from Pubmed using the keywords of H2S, smoking, and/or alcohol, this review article provides a comprehensive insight into disrupted H2S signaling by alcohol drinking and cigarette smoking-caused disorders. Major signaling and metabolic pathways involved in H2S-derived antioxidant and anti-inflammatory responses are further reviewed. H2S supplementation may prove to be an invaluable asset in treating or preventing diseases in those suffering from cigarette or alcohol addiction.

The biological and medical importance of hydrogen sulfide (H2S) has been recognized for decades. The aim of this bibliometric study is to analyze the quantity and quality of publications in H2S biology and medicine (H2SBM) based on the databases of Web of Science and Google Scholar. A total of 5881 publications published between 1990 and 2016 were analyzed. The number of H2SBM papers published before 2004 was below 100 annually, but thereafter this number rapidly increased and peaked in 2015 with more than 7-fold increase. All publications related to H2SBM research achieved a total h-index of 136 and were cited 123,074 times. The most published disciplines in H2S biomedicine research were the cardiovascular system (8.5%), neuroscience (6.5%), and gastroenterology hepatology (4.7%). The country with the greatest number of publications in the H2SBM research field was the USA with 1765 (30.0%) publications, followed by China with 995 (16.9%) publications and Japan with 555 (9.4%) publications. The top 3 most published institutes were National University of Singapore, Peking University in China, and University of Groningen in Netherlands. Nitric Oxide Biology and Chemistry was the most exploited journal for H2SBM publications with 461 articles, followed by FASEB Journal with 200 publications and Antioxidants Redox Signaling with 116 publications. The most highly cited publications and researchers in H2SBM research were also unmasked from this bibliometric analysis. Collectively, H2SBM publications exhibit a continuous trend of increase, reflecting the increased H2SBM research intensity and diversity globally.

Protein S-sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of cellular functions and metabolic pathways. By changing local conformation and the final activity of target proteins, S-sulfhydration is believed to mediate most cellular responses initiated by H2S, a novel gasotransmitter. In comparison to protein S-sulfhydration, nitric oxide-mediated protein S-nitrosylation has been extensively investigated, including its formation, regulation, transfer and metabolism. Although the investigation on the regulatory mechanisms associated with protein S-sulfhydration is still in its infancy, accumulated evidence suggested that protein S-sulfhydration may share similar chemical features with protein S-nitrosylation. Glutathione persulfide acts as a major donor for protein S-sulfhydration. Here, we review the present knowledge on protein S-sulfhydration, and also predict its formation and regulation mechanisms based on the knowledge from protein S-nitrosylation.