Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H2O2-induced oxidative damage—implications for the treatment of osteoporosis

Xu, Zhaochun; Wang, Xinyu; Xiao, Deming; Hu, Lifang; Lu, Ming; Wu, Zhiyuan; Bian, Jin-Song

doi:10.1016/j.freeradbiomed.2011.02.016

Cited by 161 publications

(114 citation statements)

References 38 publications

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“…nervous system (1). We proved that H 2 S exerted a wide range of biological functions, including neuroprotection (8,14), cardioprotection (20,21), antihypertension (13), and osteoblastic protection (37). Most of these functions are attributed to its antioxidant effects.…”

Section: Innovationmentioning

confidence: 84%

“…Cell viability was detected with the MTT method, as described previously (37). Briefly, cells were pretreated with 100 lM NaHS for 30 min, washed, and then incubated with 50 lM H 2 O 2 for 4 h. One hundred microliters of fresh medium containing 0.5 mg/ml MTT was added and incubated at 37°C for another 4 h. Finally, the culture medium containing MTT was removed.…”

Section: Cell Viability Assaymentioning

confidence: 99%

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

Xie

Shi²,

Xie³

et al. 2014

Antioxidants & Redox Signaling

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116

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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: 84%

Section: Cell Viability Assaymentioning

confidence: 99%

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

Xie

Shi²,

Xie³

et al. 2014

Antioxidants & Redox Signaling

Self Cite

116

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“…However, when the cells in our bodies suffer from harmful factors that disrupt this balance, they can be injured and eventually undergo apoptosis [18,19]. In this study, we exposed ARPE- 19 (Fig.…”

Section: H 2 O 2 and Blue Light Can Induce Cell Death And Oxidative Smentioning

confidence: 99%

PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling

Zhao

et al. 2015

Cell Physiol Biochem

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Background/Aims: Oxidative stress that damages cells of the retinal pigment epithelium (RPE) can cause the development of hereditary retinal disease (HRD). PRDX6, which is a member of the PRDX family, is essential for removing metabolic free radicals from the body. However, the effect of PRDX6 on oxidative stress in HRD remains unknown. In this study, we sought to investigate the role of PRDX6 in oxidative stress-induced HRD in ARPE-19 cells and the molecular mechanism involved. Methods: ARPE-19 cells were used in the current study. Intracellular ROS levels were determined by flow cytometry. Lipid peroxidation was measured using a commercial MDA assay kit. Cellular variability was determined by MTT assay. Apoptosis was determined using an Annexin V-FITC Apoptosis Detection Kit. mRNA and protein expression levels were detected by real-time PCR and western blot analysis, respectively. Results: We found that H₂O₂ and blue light could induce significant oxidative stress damage and cell death in ARPE-19 cells. Furthermore, we found that PRDX6 levels significantly decreased after H₂O₂ treatment. PRDX6 overexpression protected ARPE-19 cells from H₂O₂- and blue light-induced oxidative damage, while PRDX6 knockdown enhanced oxidative damage in these cells. Mechanistically, we found that PRDX6 prevented oxidative damage and promoted ARPE-19 cell survival through the PI3K/AKT signaling pathway. Conclusions: Collectively, these results suggest that PRDX6 protects ARPE-19 cells from H₂O₂-induced oxidative stress and apoptosis and that this protection is mediated at least partially through the PI3K/AKT pathway.

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“…Inhibition of nuclear transcription factor-jB (NFjB) has been reported in several models (27,28,38), and consistent with this, H 2 S reduces pro-inflammatory cytokine, chemokine, and enzyme (e.g., inducible nitric oxide synthase [iNOS]) expression (17,19,51,67). In addition, the antioxidant activity of H 2 S can be mediated by up-regulation of enzymes such as superoxide dismutase, glutathione peroxase dismutase, and thioredoxin as assessed in rats subjected to intestinal ischemia-reperfusion injury (31) or in brain endothelial cells under methionine-induced oxidative stress in vitro (53) or even by inhibition of NADPH oxidase activity, as in the case of osteoblasts exposed to hydrogen peroxide in vitro (69). With many of these putative mechanisms of action of H 2 S, it is unclear if the concentrations required for such actions are achieved in a physiological setting.…”

Section: H 2 S and Inflammationmentioning

confidence: 99%

Hydrogen Sulfide: An Endogenous Mediator of Resolution of Inflammation and Injury

Wallace

Ferraz

Muscará

2012

Antioxidants & Redox Signaling

203

148

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Significance: Hydrogen sulfide is emerging as an important mediator of many aspects of inflammation, and perhaps most importantly as a factor promoting the resolution of inflammation and repair of injury. Recent Advances: In the gastrointestinal tract, H 2 S has been shown to promote healing of ulcers and the resolution of mucosal inflammation. On the other hand, suppression of endogenous H 2 S synthesis impairs mucosal defense and leads to increased granulocyte infiltration. H 2 S has been exploited in the design of more effective and safe anti-inflammatory drugs. Critical Issues: Enteric bacteria can be a significant source of H 2 S, which could affect mucosal integrity; indeed, luminal H 2 S can serve as an alternative to oxygen as a metabolic substrate for mitochondrial respiration in epithelial cells. Enterocytes and colonocytes thereby represent a ''metabolic barrier'' to the diffusion of bacteria-derived H 2 S into the subepithelial space. A compromise of this barrier could result in modulation of mucosal function and integrity by bacterial H 2 S. Future Directions: Improvements in methods for measurement of H 2 S and development of more selective inhibitors are crucial for gaining a better understanding of the pathophysiological importance of this mediator. Results from animal studies suggest that H 2 S-releasing agents are promising therapeutic agents for many indications, but these compounds need to be assessed in a clinical setting. Antioxid. Redox Signal. 17, 58-67.

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Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H2O2-induced oxidative damage—implications for the treatment of osteoporosis

Cited by 161 publications

References 38 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

PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling

Hydrogen Sulfide: An Endogenous Mediator of Resolution of Inflammation and Injury

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