Hydrogen Sulfide in Biochemistry and Medicine

Predmore, Benjamin L.; Lefer, David J.; Gojon, Gabriel

doi:10.1089/ars.2012.4612

Cited by 344 publications

(259 citation statements)

References 240 publications

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“…Most of these functions are attributed to its antioxidant effects. This antioxidant effect of H 2 S has also been proved in a wide array of cells and tissues (16,25). The mechanisms include suppression of membrane oxidase activity [e.g., NADPH oxidase (37) and glutathione peroxidase (12)], inhibition of reactive oxygen species (ROS) production, and stimulation of synthesis of ROS scavengers [e.g., superoxide dismutase (11) and glutathione (9)].…”

Section: Innovationmentioning

confidence: 99%

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Xie

Shi²,

Xie³

et al. 2014

Antioxidants & Redox Signaling

109

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Aims: Mitochondrion is considered as the major source of intracellular reactive oxygen species (ROS). H 2 S has been reported to be an antioxidant, but its mechanism remains largely elusive. P66Shc is an upstream activator of mitochondrial redox signaling. The aim of this study was to explore whether the antioxidant effect of H 2 S is mediated by p66Shc. Results: Application of exogenous H 2 S with its donor, NaHS, or overexpression of its generating enzyme, cystathionine b-synthase, induced sulfhydration of p66Shc, but inhibited its phosphorylation caused by H 2 O 2 /D-galactose in SH-SY5Y cells or in the mice cortex. H 2 S also decreased mitochondrial ROS production and protected neuronal cells against stress-induced senescence. PKC bII and PP2A are the two key proteins to regulate p66Shc phosphorylation. Although H 2 S failed to affect the activities of these two proteins, it disrupted their association. Cysteine-59 resides in proximity to serine-36, the phosphorylation site of p66Shc. The C59S mutant attenuated the above-described biological function of H 2 S. Innovation: We revealed a novel mechanism for the antioxidant effect of H 2 S and its role in oxidative stress-related diseases. Conclusion: H 2 S inhibits mitochondrial ROS production via the sulfhydration of Cys-59 residue, which in turn, prevents the phosphorylation of p66Shc. Antioxid. Redox Signal. 21, 2531-2542.

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Section: Innovationmentioning

confidence: 99%

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Xie

Shi²,

Xie³

et al. 2014

Antioxidants & Redox Signaling

109

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“…The physiological functions of H 2 S are mediated by a variety of molecular targets, including ion channels and signaling proteins (16)(17)(18). Alterations in H 2 S metabolism contribute to an array of cardiovascular disorders such as hypertension, atherosclerosis, heart failure, and diabetes (19). Nevertheless, the influence of H 2 S on platelet function and, in turn, on blood clotting has been poorly explored.…”

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confidence: 99%

Hydrogen sulphide pathway contributes to the enhanced human platelet aggregation in hyperhomocysteinemia

Bianca

Mitidieri

Minno

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Homocysteine is metabolized to methionine by the action of 5,10methylenetetrahydrofolate reductase (MTHFR). Alternatively, by thetransulfuration pathway, homocysteine is transformed to hydrogen sulphide (H2S),through multiple steps involving cystathionine beta-synthase and cystathioninegamma-lyase. Here we have evaluated the involvement of H2S in the thromboticevents associated with hyperhomocysteinemia. To this purpose we have usedplatelets harvested from healthy volunteers or patients newly diagnosed withhyperhomocysteinemia with a C677T polymorphism of the MTHFR gene (MTHFR++). NaHS(0.1-100 microM) or l-cysteine (0.1-100 microM) significantly increased plateletaggregation harvested from healthy volunteers induced by thrombin receptoractivator peptide-6 amide (2 microM) in a concentration-dependent manner. Thisincrease was significantly potentiated in platelets harvested from MTHFR++carriers, and it was reversed by the inhibition of either cystathioninebeta-synthase or cystathionine gamma-lyase. Similarly, in MTHFR++ carriers, thecontent of H2S was significantly higher in either platelets or plasma comparedwith healthy volunteers. Interestingly, thromboxane A2 production was markedlyincreased in response to both NaHS or l-cysteine in platelets of healthyvolunteers. The inhibition of phospholipase A2, cyclooxygenase, or blockade ofthe thromboxane receptor markedly reduced the effects of H2S. Finally,phosphorylated-phospholipase A2 expression was significantly higher in MTHFR++carriers compared with healthy volunteers. In conclusion, the H2S pathway isinvolved in the prothrombotic events occurring in hyperhomocysteinemic patients

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“…Under these conditions, the 3 gases have the ability to synergize their anti‐apoptotic, anti‐inflammatory, and antihypertrophic effects, which lead to cardioprotection. Although H 2 S and NO are thought to modulate independent pathways, there is evidence of cross‐talk between these 2 signaling molecules 35, 36. Our laboratory previously demonstrated that treatment with exogenous H 2 S or modulation of the endogenous production of H 2 S through the cardiac‐specific overexpression of the H 2 S‐generating enzyme CSE protects against acute MI/R injury and HF by attenuating oxidative stress, inhibiting apoptosis, and reducing inflammation 34, 37.…”

Section: Introductionmentioning

confidence: 99%

Nitrite Therapy Ameliorates Myocardial Dysfunction via H ₂ S and Nuclear Factor‐Erythroid 2‐Related Factor 2 (Nrf2)‐Dependent Signaling in Chronic Heart Failure

Donnarumma

Bhushan

Bradley

et al. 2016

JAHA

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BackgroundBioavailability of nitric oxide (NO) and hydrogen sulfide (H2S) is reduced in heart failure (HF). Recent studies suggest cross‐talk between NO and H2S signaling. We previously reported that sodium nitrite (NaNO 2) ameliorates myocardial ischemia‐reperfusion injury and HF. Nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) regulates the antioxidant proteins expression and is upregulated by H2S. We examined the NaNO 2 effects on endogenous H2S bioavailability and Nrf2 activation in mice subjected to ischemia‐induced chronic heart failure (CHF).Methods and ResultsMice underwent 60 minutes of left coronary artery occlusion and 4 weeks of reperfusion. NaNO 2 (165 μg/kgic) or vehicle was administered at reperfusion and then in drinking water (100 mg/L) for 4 weeks. Left ventricular (LV), ejection fraction (EF), LV end diastolic (LVEDD) and systolic dimensions (LVESD) were determined at baseline and at 4 weeks of reperfusion. Myocardial tissue was analyzed for oxidative stress and respective gene/protein‐related assays. We found that NaNO 2 therapy preserved LVEF, LVEDD and LVSD at 4 weeks during ischemia‐induced HF. Myocardial malondialdehyde and protein carbonyl content were significantly reduced in NaNO 2‐treated mice as compared to vehicle, suggesting a reduction in oxidative stress. NaNO 2 therapy markedly increased expression of Cu,Zn‐superoxide dismutase, catalase, and glutathione peroxidase during 4 weeks of reperfusion. Furthermore, NaNO 2 upregulated the activity of Nrf2, as well as H2S‐producing enzymes, and ultimately increased H2S bioavailability in ischemia‐induced CHF in mice as compared with vehicle.ConclusionsOur results demonstrate that NaNO 2 therapy significantly improves LV function via increasing H2S bioavailability, Nrf2 activation, and antioxidant defenses.

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Hydrogen Sulfide in Biochemistry and Medicine

Cited by 344 publications

References 240 publications

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Hydrogen sulphide pathway contributes to the enhanced human platelet aggregation in hyperhomocysteinemia

Nitrite Therapy Ameliorates Myocardial Dysfunction via H ₂ S and Nuclear Factor‐Erythroid 2‐Related Factor 2 (Nrf2)‐Dependent Signaling in Chronic Heart Failure

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Hydrogen Sulfide in Biochemistry and Medicine

Cited by 344 publications

References 240 publications

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Hydrogen sulphide pathway contributes to the enhanced human platelet aggregation in hyperhomocysteinemia

Nitrite Therapy Ameliorates Myocardial Dysfunction via H 2 S and Nuclear Factor‐Erythroid 2‐Related Factor 2 (Nrf2)‐Dependent Signaling in Chronic Heart Failure

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Product

Resources

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Nitrite Therapy Ameliorates Myocardial Dysfunction via H ₂ S and Nuclear Factor‐Erythroid 2‐Related Factor 2 (Nrf2)‐Dependent Signaling in Chronic Heart Failure