Antioxidants & redox signaling
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Antioxid. Redox Signal. · Nov 2017
Age-Dependent Allergic Asthma Development and Cystathionine Gamma-Lyase Deficiency.
The pathogenic mechanisms for the higher prevalence of allergic asthma in children than in adults have not been settled. The aim of the present study is to examine whether the age-dependent development of allergic asthma is caused by age-dependent expression of cystathionine gamma-lyase (CSE), a key enzyme that catalyzes the production of hydrogen sulfide (H2S). ⋯ Allergic asthma was induced with ovalbumin in wild-type (WT) and CSE knock-out (KO) mice at young and old ages. CSE expression and H2S production were lower in immune cells of young WT mice than in those of old WT mice. Coincidentally, more severe asthmatic symptoms with a greater type-2 immunoreaction were found in young WT mice than old WT mice. H2S supplementation reversed the asthmatic symptoms. Lower expression levels of CSE proteins were also found in human umbilical cord blood mononuclear cells in comparison with that of peripheral blood mononuclear cells from adult people. The age-dependent asthma propensity vanished in CSE-KO mice, but these mice developed more severe asthma than WT mice. More splenocytes were differentiated to type-2 cytokine-generating cells in young WT mice and in CSE-KO mice at all ages. This differentiation was inhibited by H2S donors. GATA3 translocation to the nucleus and type-2 immunoreaction of splenocytes were inhibited after GATA3 was S-sulfhydrated by H2S. Innovation and Conclusion: For the first time, this study demonstrated that lower abundance of CSE expression and H2S production enhances type-2 immunoreaction and renders a higher incidence of allergic asthma at a young age. As such, H2S level may be a biomarker for asthma development and a H2S-based strategy can be perceived for asthma prevention and treatment. Antioxid. Redox Signal. 27, 931-944.
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Antioxid. Redox Signal. · Oct 2017
Cystathionine γ-Lyase-Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing.
Hydrogen sulfide (H2S) plays an essential role in bone formation, in part, by inhibiting osteoclast differentiation, maintaining mesenchymal stem cell osteogenesis ability, or reducing osteoblast injury. We aimed to investigate the role of H2S in osteoblast function and its possible molecular target. ⋯ CSE-H2S sulfhydrated RUNX2 enhanced its transactivation and increased osteoblast differentiation and maturation, thereby promoting bone healing. Antioxid. Redox Signal. 27, 742-753.
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Antioxid. Redox Signal. · Sep 2017
The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-κB/Nuclear Transcription Factor Related to NF-E2.
Oxidative stress plays a key role in Parkinson disease (PD), and nuclear transcription factor related to NF-E2 (Nrf-2) is involved in neuroprotection against PD. The aim of the present study was to investigate a role for nuclear factor-κB (NF-κB)/Nrf-2 in the neurotherapeutic action of dimethyl fumarate (DMF) in a mouse model of PD and in vitro in SHSY-5Y cells. ⋯ These results support the thesis that DMF may constitute a promising therapeutic target for the treatment of PD. Antioxid. Redox Signal. 27, 453-471.
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Antioxid. Redox Signal. · Sep 2017
Augmentation of S-Nitrosoglutathione Controls Cigarette Smoke-Induced Inflammatory-Oxidative Stress and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis by Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function.
Cigarette smoke (CS)-mediated acquired cystic fibrosis transmembrane conductance regulator (CFTR)-dysfunction, autophagy-impairment, and resulting inflammatory-oxidative/nitrosative stress leads to chronic obstructive pulmonary disease (COPD)-emphysema pathogenesis. Moreover, nitric oxide (NO) signaling regulates lung function decline, and low serum NO levels that correlates with COPD severity. Hence, we aim to evaluate here the effects and mechanism(s) of S-nitrosoglutathione (GSNO) augmentation in regulating inflammatory-oxidative stress and COPD-emphysema pathogenesis. ⋯ Overall, we found that augmenting GSNO levels controls COPD-emphysema pathogenesis by reducing CS-induced acquired CFTR dysfunction and resulting autophagy impairment and chronic inflammatory-oxidative stress. Antioxid. Redox Signal. 27, 433-451.
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Antioxid. Redox Signal. · Jul 2017
Cystathionine γ-Lyase Deficiency Exacerbates CCl4-Induced Acute Hepatitis and Fibrosis in the Mouse Liver.
The present study examined the role of cystathionine γ-lyase (CSE) in carbon tetrachloride (CCl4)-induced liver damage. ⋯ CSE deficiency increases pro-inflammatory cytokines in the liver and exacerbates acute hepatitis and liver fibrosis by reducing H2S production from L-cysteine in the liver. The present data suggest the potential of an H2S donor for the treatment of liver diseases such as toxic hepatitis and fibrosis. Antioxid. Redox Signal. 27, 133-149.