Neglected role of hydrogen sulfide in sulfur mustard poisoning: Keap1 S-sulfhydration and subsequent Nrf2 pathway activation

Meng, Wenqi; Pei, Zhipeng; Feng, Yi; Zhao, Jie; Chen, Yongchun; Shi, Wenwen; Xu, Quyi; Lin, Fengwu; Sun, Mingxue; Xiao, Kai

doi:10.1038/s41598-017-09648-6

Cited by 38 publications

(21 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, PAG administration further exacerbated lung injuries. Moreover, Meng et al (2017) also documented that PAG has exacerbated lung damage through reduction of endogenous H 2 S level, CSE expression and Nrf2 nuclear translocation which was associated with increased oxidative stress markers. Zhao et al (2014) reported that H 2 S donors have been widely used in the field.…”

Section: Immunohistochemical Assessment Of Inosmentioning

confidence: 90%

H2S attenuates acute lung inflammation induced by administration of lipopolysaccharide in adult male rats

Ali¹,

Abdel-Hamid²,

Toni³

2018

gpb

View full text Add to dashboard Cite

. Hydrogen sulfide (H2S) is gasotransmitter which plays an important role in human physiology. In this study, we aimed to check the effect of H2S treatment on acute lung inflammation (ALI). Thirty-six adult male albino rats were used and divided into: control group, ALI group which was intraperitoneally (i.p.) injected with lipopolysaccharide (LPS) at a dose of 5 mg/kg body weight, ALI group treated by the H2S donor; sodium hydrosulfide (NaHS) at a dose of 10 mg/kg body weight i.p. and ALI group treated by i.p. injection of 80 mg/kg body weight DL- propargylglycine (PAG) which is an inhibitor of endogenous H2S synthesis. Serum was obtained to determine interleukin-6 (IL-6) levels. Lipid peroxides and total antioxidant capacity (TAC) levels were measured in lung. Lung histopathology and expression of inducible nitric oxide synthase (iNOS) were also done. Results showed that NaHS improved lung inflammation through its inhibitory effect on iNOS expression, decreasing the levels of IL-6 and lipid peroxides and increasing TAC levels. But, ALI was exacerbated with PAG administration. In conclusion, the results proved that H2S has a protective effect against LPS induced ALI due to its anti-nitrative, anti-oxidant and anti-inflammatory properties.

show abstract

Section: Immunohistochemical Assessment Of Inosmentioning

confidence: 90%

H2S attenuates acute lung inflammation induced by administration of lipopolysaccharide in adult male rats

Ali¹,

Abdel-Hamid²,

Toni³

2018

gpb

View full text Add to dashboard Cite

show abstract

“…The present experiments show that simple but specific hydroxybenzenes can oxidize H 2 S to polysulfides after the former are themselves autoxidized. These results help to explain the mechanism behind the health benefits of many nutraceutical polyphenols; polysulfides produced by the oxidation of H 2 S are potent antioxidants [ 17 ], they may scavenge superoxide [ 42 ], and through their ability to persulfidate Keap1, they free it from Nrf2, which can then activate nuclear antioxidant response elements [ 18 , 19 , 43 , 44 , 45 , 46 ]. Our experiments also show that the ability of hydroxybenzenes to oxidize H 2 S varies considerably with the location and distribution of these hydroxyl groups and that the addition of specific side groups can further alter the reactivity of these compounds.…”

Section: Discussionmentioning

confidence: 99%

Oxidation of Hydrogen Sulfide by Quinones: How Polyphenols Initiate Their Cytoprotective Effects

Olson

Gao

Straub

2021

IJMS

View full text Add to dashboard Cite

We have shown that autoxidized polyphenolic nutraceuticals oxidize H2S to polysulfides and thiosulfate and this may convey their cytoprotective effects. Polyphenol reactivity is largely attributed to the B ring, which is usually a form of hydroxyquinone (HQ). Here, we examine the effects of HQs on sulfur metabolism using H2S- and polysulfide-specific fluorophores (AzMC and SSP4, respectively) and thiosulfate sensitive silver nanoparticles (AgNP). In buffer, 1,4-dihydroxybenzene (1,4-DB), 1,4-benzoquinone (1,4-BQ), pyrogallol (PG) and gallic acid (GA) oxidized H2S to polysulfides and thiosulfate, whereas 1,2-DB, 1,3-DB, 1,2-dihydroxy,3,4-benzoquinone and shikimic acid did not. In addition, 1,4-DB, 1,4-BQ, PG and GA also increased polysulfide production in HEK293 cells. In buffer, H2S oxidation by 1,4-DB was oxygen-dependent, partially inhibited by tempol and trolox, and absorbance spectra were consistent with redox cycling between HQ autoxidation and H2S-mediated reduction. Neither 1,2-DB, 1,3-DB, 1,4-DB nor 1,4-BQ reduced polysulfides to H2S in either 21% or 0% oxygen. Epinephrine and norepinephrine also oxidized H2S to polysulfides and thiosulfate; dopamine and tyrosine were ineffective. Polyphenones were also examined, but only 2,5-dihydroxy- and 2,3,4-trihydroxybenzophenones oxidized H2S. These results show that H2S is readily oxidized by specific hydroxyquinones and quinones, most likely through the formation of a semiquinone radical intermediate derived from either reaction of oxygen with the reduced quinones, or from direct reaction between H2S and quinones. We propose that polysulfide production by these reactions contributes to the health-promoting benefits of polyphenolic nutraceuticals.

show abstract

“…Long-term benefits of polysulfides are also derived from their modulation of antioxidant response mechanisms. Polysulfides increase intracellular antioxidant activity via persulfidation of Keap1 which causes Keap1 to dissociate from Nrf2, similar to the proposed mechanism of Keap-1 peroxidation [34][35][36][37][38][39]. Nrf2 then translocates to the nucleus where it activates the suite of cytoprotective antioxidant response elements [40,41].…”

Section: Antioxidant Function Of Mnp-generated Polysulfidesmentioning

confidence: 85%

Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

et al. 2020

View full text Add to dashboard Cite

Manganese porphyrins (MnPs), MnTE-2-PyP5+, MnTnHex-2-PyP5+ and MnTnBuOE-2-PyP5+, are superoxide dismutase (SOD) mimetics and form a redox cycle between O2 and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (H2O2). We previously found that MnPs oxidize hydrogen sulfide (H2S) to polysulfides (PS; H2Sn, n = 2–6) in buffer. Here, we examine the effects of MnPs for 24 h on H2S metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using H2S (AzMC, MeRho-AZ) and PS (SSP4) fluorophores. All MnPs decreased intracellular H2S production and increased intracellular PS. H2S metabolism and PS production were unaffected by cellular O2 (5% versus 21% O2), H2O2 or ascorbic acid. We observed with confocal microscopy that mitochondria are a major site of H2S production in HEK293 cells and that MnPs decrease mitochondrial H2S production and increase PS in what appeared to be nucleoli and cytosolic fibrillary elements. This supports a role for MnPs in the metabolism of H2S to PS, the latter serving as both short- and long-term antioxidants, and suggests that some of the biological effects of MnPs may be attributable to sulfur metabolism.

show abstract

Neglected role of hydrogen sulfide in sulfur mustard poisoning: Keap1 S-sulfhydration and subsequent Nrf2 pathway activation

Cited by 38 publications

References 59 publications

H2S attenuates acute lung inflammation induced by administration of lipopolysaccharide in adult male rats

H2S attenuates acute lung inflammation induced by administration of lipopolysaccharide in adult male rats

Oxidation of Hydrogen Sulfide by Quinones: How Polyphenols Initiate Their Cytoprotective Effects

Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

Contact Info

Product

Resources

About