The production and role of hydrogen sulfide and hydrogen polysulfides in mammalian cells

Hydrogen sulfide (H2S) has emerged as a relevant signaling molecule in physiology, taking its seat as a bona fide gasotransmitter akin to nitric oxide (NO) and carbon monoxide (CO). After being merely regarded as a toxic poisonous molecule, it is now recognized that mammalian cells are equipped with sophisticated enzymatic systems for H2S production and breakdown. The signaling role of H2S is mainly related to its ability to modify different protein targets, particularly by promoting persulfidation of protein cysteine residues and by interacting with metal centers, mostly hemes. H2S has been shown to regulate a myriad of cellular processes with multiple physiological consequences. As such, dysfunctional H2S metabolism is increasingly implicated in different pathologies, from cardiovascular and neurodegenerative diseases to cancer. As a highly diffusible reactive species, the intra- and extracellular levels of H2S have to be kept under tight control and, accordingly, regulation of H2S metabolism occurs at different levels. Interestingly, even though H2S, NO, and CO have similar modes of action and parallel regulatory targets or precisely because of that, there is increasing evidence of a crosstalk between the three gasotransmitters. Herein are reviewed the biochemistry, metabolism, and signaling function of hydrogen sulfide, as well as its interplay with the other gasotransmitters, NO and CO.

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The Role of Hydrogen Peroxide in Redox-Dependent Signaling: Homeostatic and Pathological Responses in Mammalian Cells

Cells ◽

10.3390/cells7100156 ◽

2018 ◽

Vol 7 (10) ◽

pp. 156 ◽

Cited By ~ 39

Author(s):

Noemi Di Marzo ◽

Elisa Chisci ◽

Roberto Giovannoni

Keyword(s):

Nitric Oxide ◽

Hydrogen Peroxide ◽

Hydrogen Sulfide ◽

Mammalian Cells ◽

Metabolic Response ◽

Second Messengers ◽

Cellular Systems ◽

Eukaryotic Cells ◽

Redox Metabolism

Hydrogen peroxide (H2O2) is an important metabolite involved in most of the redox metabolism reactions and processes of the cells. H2O2 is recognized as one of the main molecules in the sensing, modulation and signaling of redox metabolism, and it is acting as a second messenger together with hydrogen sulfide (H2S) and nitric oxide (NO). These second messengers activate in turn a cascade of downstream proteins via specific oxidations leading to a metabolic response of the cell. This metabolic response can determine proliferation, survival or death of the cell depending on which downstream pathways (homeostatic, pathological, or protective) have been activated. The cells have several sources of H2O2 and cellular systems strictly control its concentration in different subcellular compartments. This review summarizes research on the role played by H2O2 in signaling pathways of eukaryotic cells and how this signaling leads to homeostatic or pathological responses.

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Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00489.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. L1193-L1201 ◽

Cited By ~ 124

Author(s):

Huili Zhang ◽

Liang Zhi ◽

Philip K. Moore ◽

Madhav Bhatia

Keyword(s):

Hydrogen Sulfide ◽

Systemic Inflammation ◽

Mammalian Cells ◽

Cecal Ligation ◽

Organ Injury ◽

Sham Operation ◽

Myeloperoxidase Activity ◽

Cecal Ligation And Puncture ◽

Sodium Hydrosulfide

Endogenous hydrogen sulfide (H2S) is naturally synthesized in various types of mammalian cells from l-cysteine in a reaction catalyzed by two enzymes, cystathionine-γ-lyase (CSE) and/or cystathionine-β-synthase. The latest studies have implied that H2S functions as a vasodilator and neurotransmitter. However, so far there is little information about the role played by H2S in systemic inflammation such as sepsis. Thus the aim of this study was to investigate the potential role of endogenous H2S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP-induced sepsis and treated with saline (ip), dl-propargylglycine (PAG, 50 mg/kg ip), a CSE inhibitor, or sodium hydrosulfide (NaHS; 10 mg/kg ip). PAG was administered either 1 h before or 1 h after the induction of sepsis, whereas NaHS was given at the same time of CLP. CLP-induced sepsis significantly increased the plasma H2S level and the liver H2S synthesis 8 h after CLP compared with sham operation. Induction of sepsis also resulted in a significant upregulation of CSE mRNA in liver. On the other hand, prophylactic as well as therapeutic administration of PAG significantly reduced sepsis-associated systemic inflammation, as evidenced by myeloperoxidase activity and histological changes in lung and liver, and attenuated the mortality of CLP-induced sepsis. Injection of NaHS significantly aggravated sepsis-associated systemic inflammation. Therefore, the effect of inhibition of H2S formation and administration of NaHS suggests that H2S plays a proinflammatory role in regulating the severity of sepsis and associated organ injury.

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Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed

Physiological Reviews ◽

10.1152/physrev.00017.2011 ◽

2012 ◽

Vol 92 (2) ◽

pp. 791-896 ◽

Cited By ~ 1038

Author(s):

Rui Wang

Keyword(s):

Heart Failure ◽

Hydrogen Sulfide ◽

Erectile Dysfunction ◽

Mammalian Cells ◽

New Technologies ◽

Molecular Targets ◽

Signaling Proteins ◽

Physiological Functions ◽

Physiological Importance

The important life-supporting role of hydrogen sulfide (H2S) has evolved from bacteria to plants, invertebrates, vertebrates, and finally to mammals. Over the centuries, however, H2S had only been known for its toxicity and environmental hazard. Physiological importance of H2S has been appreciated for about a decade. It started by the discovery of endogenous H2S production in mammalian cells and gained momentum by typifying this gasotransmitter with a variety of physiological functions. The H2S-catalyzing enzymes are differentially expressed in cardiovascular, neuronal, immune, renal, respiratory, gastrointestinal, reproductive, liver, and endocrine systems and affect the functions of these systems through the production of H2S. The physiological functions of H2S are mediated by different molecular targets, such as different ion channels and signaling proteins. Alternations of H2S metabolism lead to an array of pathological disturbances in the form of hypertension, atherosclerosis, heart failure, diabetes, cirrhosis, inflammation, sepsis, neurodegenerative disease, erectile dysfunction, and asthma, to name a few. Many new technologies have been developed to detect endogenous H2S production, and novel H2S-delivery compounds have been invented to aid therapeutic intervention of diseases related to abnormal H2S metabolism. While acknowledging the challenges ahead, research on H2S physiology and medicine is entering an exponential exploration era.

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An Anticancer Role of Hydrogen Sulfide in Human Gastric Cancer Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/636410 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Li Zhang ◽

Qi Qi ◽

Jianqiang Yang ◽

Dongsheng Sun ◽

Chunfeng Li ◽

...

Keyword(s):

Gastric Cancer ◽

Hydrogen Sulfide ◽

Cancer Cells ◽

Mammalian Cells ◽

Migration And Invasion ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Induced Apoptosis ◽

Related Proteins

Hydrogen sulfide (H2S) can be synthesized in mammalian cells by cystathionineγ-lyase (CSE) and/or cystathionineβ-synthase (CBS). Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated.

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The production and role of hydrogen sulfide and hydrogen polysulfides in mammalian cells

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.92.0_2-p-102 ◽

2019 ◽

Vol 92 (0) ◽

pp. 2-P-102

Author(s):

Norihiro Shibuya ◽

Shin Koike ◽

Yuka Kimura ◽

Ryo Miyamoto ◽

Yuki Ogasawara ◽

...

Keyword(s):

Hydrogen Sulfide ◽

Mammalian Cells

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GASOMEDIATOR H2S IN THROMBOSIS AND HEMOSTASIS

Biotechnologia Acta ◽

10.15407/biotech13.06.024 ◽

2020 ◽

Vol 13 (6) ◽

pp. 24-29

Author(s):

Nadiya Druzhyna ◽

Keyword(s):

Hydrogen Sulfide ◽

Mammalian Cells ◽

Current Knowledge ◽

Platelet Reactivity ◽

Thrombus Formation ◽

Blood Platelet ◽

Cell Physiology ◽

Biologically Relevant ◽

And Function

This review was aimed to briefly summarize current knowledge of the biological roles of gasomediator H2S in hemostasis and cardiovascular diseases. Since the discovery that mammalian cells are enzymatically producing H2S, this molecule underwent a dramatic metamorphosis from dangerous pollutant to a biologically relevant mediator. As a gasomediator, hydrogen sulfide plays a role of signaling molecule, which is involved in a number of processes in health and disease, including pathogenesis of cardiovascular abnormalities, mainly through modulating different patterns of vasculature functions and thrombotic events. Recently, several studies have provided unequivocal evidence that H2S reduces blood platelet reactivity by inhibiting different stages of platelet activation (platelet adhesion, secretion and aggregation) and thrombus formation. Moreover, H2S changes the structure and function of fibrinogen and proteins associated with fibrinolysis. Hydrogen sulfide regulates proliferation and apoptosis of vascular smooth muscle cells, thus modulating angiogenesis and vessel function. Undoubtedly, H2S is also involved in a multitude of other physiological functions. For example, it exhibits anti-inflammatory effects by inhibiting ROS production and increasing expression of antioxidant enzymes. Some studies have demonstrated the role of hydrogen sulfide as a therapeutic agent in various diseases, including cardiovascular pathologies. Further studies are required to evaluate its importance as a regulator of cell physiology and associated cardiovascular pathological conditions such as myocardial infarction and stroke.

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