Hydrogen sulfide: An endogenous regulator of the immune system

Dilek, Nahzli; Papapetropoulos, Andreas; Toliver‐Kinsky, Tracy; Szabó, Csaba

doi:10.1016/j.phrs.2020.105119

Cited by 197 publications

(131 citation statements)

References 527 publications

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“…The immune cells are in permanent contact with H 2 S because of the endogenous and exogenous production from the surrounding parenchymal cells, which regulates their viability and function. The downregulation or genetic defect in endogenous H 2 Sproducing enzymes leads to the onset or development of autoimmune diseases [103]. Monocytes/macrophages express CBS, CSE and MST, and CSE and MST are likely the primary enzymes.…”

Section: H 2 S In Immune Cellsmentioning

confidence: 99%

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

Paganelli

Mottola

Fromonot

et al. 2021

IJMS

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The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.

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Section: H 2 S In Immune Cellsmentioning

confidence: 99%

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

Paganelli

Mottola

Fromonot

et al. 2021

IJMS

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“…In particular, the production of GSH from l -cysteine is driven by γ -glutamylcysteine synthetase (γ-GCS) and glutathione synthase (GS) enzymes; while l -taurine is produced by the subsequential action of other three enzymes named cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD) and hypotaurine dehydrogenase (HDD) ( Fig. 1 ) [ 10 , 16 , 17 ]. In addition to its essential role in protein synthesis, l -cysteine is also a component of the major antioxidant GSH and a potent antioxidant itself.…”

Section: Introductionmentioning

confidence: 99%

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

et al. 2021

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Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked disease caused by mutations in the gene encoding for dystrophin, leading to progressive and unstoppable degeneration of skeletal muscle tissues. Despite recent advances in the understanding of the molecular processes involved in the pathogenesis of DMD, there is still no cure. In this study, we aim at investigating the potential involvement of the transsulfuration pathway (TSP), and its by-end product namely hydrogen sulfide (H 2 S), in primary human myoblasts isolated from DMD donors and skeletal muscles of dystrophic ( mdx ) mice. In myoblasts of DMD donors, we demonstrate that the expression of key genes regulating the H 2 S production and TSP activity, including cystathionine γ lyase (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), glutathione synthase (GS) and γ -glutamylcysteine synthetase (γ-GCS) is reduced. Starting from these findings, using Nuclear Magnetic Resonance (NMR) and quantitative Polymerase Chain Reaction (qPCR) we show that the levels of TSP-related metabolites such as methionine, glycine, glutathione, glutamate and taurine, as well as the expression levels of the aforementioned TSP related genes, are significantly reduced in skeletal muscles of mdx mice compared to healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly used H 2 S donor, fully recovers the impaired locomotor activity in both 7 and 17 old mdx mice. This is an effect attributable to the reduced expression of pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. In conclusion, our study uncovers a defective TSP pathway activity in DMD and highlights the role of H 2 S-donors for novel and safe adjuvant therapy to treat symptoms of DMD.

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“…For instance, H 2 S has been reported to inhibit the adherence of leukocytes to blood vessel walls [10]. This simple inorganic molecule has also been shown to have a vasodilatory effect, similar to its sister endogenous gaseous mediators, carbon monoxide (CO) and nitric oxide (NO) [11][12][13][14][15]. H 2 S is produced endogenously by the metabolism of L-cysteine, mainly with the involvement of two pyridoxal-5-phosphate (P5P, vitamin B6)-dependent enzymes: cystathionine-γ-lyase (CTH) and cystathionine-β-synthase (CBS) [16,17].…”

Section: Introductionmentioning

confidence: 99%

Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier

Bakalarz

Korbut

Yuan

et al. 2021

IJMS

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Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5–50 μmol/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 μmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.

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Hydrogen sulfide: An endogenous regulator of the immune system

Cited by 197 publications

References 527 publications

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier

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