The role of hydrogen sulfide in burns

Akter, Farhana

doi:10.1016/j.burns.2015.07.005

Cited by 29 publications

(26 citation statements)

References 29 publications

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“…Despite the controversial role initially attributed to H 2 S, it is to date recognized that, at low concentrations, it exhibits anti-apoptotic, anti-nociceptive, cardio-protective, and blood pressure-lowering effects, while also improving angiogenesis, via the activation of K ATP channels and extracellular signal-regulated kinases, such as Akt pathways [1,[17][18][19][20][21][22]. Moreover, H 2 S shows neuroprotective and anti-inflammatory effects in general due to its antioxidant effects and inhibition of pro-inflammatory cytokines [23][24][25][26][27][28]. The potential effects of H 2 S were also discussed in several review articles [29][30][31][32] and are here summarized in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

Sunzini

Stefano

Chimenti

et al. 2020

IJMS

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The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H 2 S) were recently demonstrated in the context of different inflammatory diseases. In particular, H 2 S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H 2 S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H 2 S, more evidence is needed to understand the pathophysiology and the potential of H 2 S as a therapeutic agent. Within this review, we provide an overview on H 2 S biological effects, on its role in immune-mediated inflammatory diseases, on H 2 S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.

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Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

Sunzini

Stefano

Chimenti

et al. 2020

IJMS

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“…Fifth, the mechanism(s) and source(s) of H 2 S responsible for the endogenous sulfhydration of the enzyme remain to be identified; the experiments using CSE −/− mice indicate that CSE plays an important role; the roles of the other two H 2 S-generating enzymes (CBS and 3-MST) remain to be explored. Sixth, the role of the increased sulfhydration of ATP synthase – in light of the complex pathomechanisms of burn injury, and the multiple potential roles of H 2 S in burns [57] – remain to be characterized. Seventh, the current ex vivo studies only investigated one selected organ (the liver); it remains to be examined whether S -sulfhydration of ATP synthase occurs in other organs as well, and if it does, what functional role does it play.…”

Section: Discussionmentioning

confidence: 99%

S- Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics

Módis

Ahmad

et al. 2016

Pharmacological Research

170

113

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Mammalian cells can utilize hydrogen sulfide (H2S) to support mitochondrial respiration. The aim of our study was to explore the potential role of S-sulfhydration (a H2S-induced posttranslational modification, also known as S-persulfidation) of the mitochondrial inner membrane protein ATP synthase (F1F0 ATP synthase/Complex V) in the regulation of mitochondrial bioenergetics. Using a biotin switch assay, we have detected S-sulfhydration of the α subunit (ATP5A1) of ATP synthase in response to exposure to H2S in vitro. The H2S generator compound NaHS induced S-sulfhydration of ATP5A1 in HepG2 and HEK293 cell lysates in a concentration-dependent manner (50–300 μM). The activity of immunocaptured mitochondrial ATP synthase enzyme isolated from HepG2 and HEK293 cells was stimulated by NaHS at low concentrations (10–100 nM). Site-directed mutagenesis of ATP5A1 in HEK293 cells demonstrated that cysteine residues at positions 244 and 294 are subject to S-sulfhydration. The double mutant ATP synthase protein (C244S/C294S) showed a significantly reduced enzyme activity compared to control and the single-cysteine-mutated recombinant proteins (C244S or C294S). To determine whether endogenous H2S plays a role in the basal S-sulfhydration of ATP synthase in vivo, we compared liver tissues harvested from wild-type mice and mice deficient in cystathionine-gamma-lyase (CSE, one of the three principal mammalian H2S-producing enzymes). Significantly reduced S-sulfhydration of ATP5A1 was observed in liver homogenates of CSE−/− mice, compared to wild-type mice, suggesting a physiological role for CSE-derived endogenous H2S production in the S-sulfhydration of ATP synthase. Various forms of critical illness (including burn injury) upregulate H2S-producing enzymes and stimulate H2S biosynthesis. In liver tissues collected from mice subjected to burn injury, we detected an increased S-sulfhydration of ATP5A1 at the early time points post-burn. At later time points (when systemic H2S levels decrease) S-sulfhydration of ATP5A1 decreased as well. In conclusion, H2S induces S-sulfhydration of ATP5A1 at C244 and C294. This post-translational modification may be a physiological mechanism to maintain ATP synthase in a physiologically activated state, thereby supporting mitochondrial bioenergetics. The sulfhydration of ATP synthase may be a dynamic process, which may be regulated by endogenous H2S levels under various pathophysiological conditions.

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“…"H 2 S-Rich" and "H 2 S-Poor" Pathophysiological Conditions H 2 S has been implicated in the pathogenesis of multiple diseases, as overviewed in review articles. These range from cardiovascular diseases (e.g., myocardial reperfusion injury, cardiac hypertrophy, heart failure, atherosclerosis, hypertension) (Predmore et al, 2012b;Polhemus and Lefer, 2014;Ahmad et al, 2015;Meng et al, 2015aMeng et al, , 2016Shen et al, 2015;Wang et al, 2015a;Cao and Bian, 2016;Kanagy et al, 2017;Greaney et al, 2017) to various neurologic diseases (e.g., stroke, neuroinflammation) (Wang et al, 2014a;Bhatia, 2015;Kida and Ichinose, 2015;Wallace et al, 2015;Sen, 2017) and metabolic diseases (e.g., diabetes mellitus) (Desai et al, 2011;Szabo, 2012;Okamoto et al, 2015;Carter and Morton, 2016) to various forms of local and systemic inflammation (e.g., hemorrhagic shock, septic H 2 S Donors and H 2 S Biosynthesis Inhibitors shock, burn injury) (Wagner et al, 2009;Coletta and Szabo, 2013;McCook et al, 2014;Akter, 2016).…”

Section: H 2 S As An Endogenous Biologic Mediatormentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

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The role of hydrogen sulfide in burns

Cited by 29 publications

References 29 publications

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

S- Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

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The role of hydrogen sulfide in burns

Cited by 29 publications

References 29 publications

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

S- Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors