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hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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hydrogen sulfide Detection Using a Gold Nanoparticle/Metalloprotein Based Probe

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Chinese Physics Letters 2014年第8期31卷 170-173页

作者： MeisamOmidi FaeultyofNewScienceandTechnologyUniversityofTehran TehranIran ResearchCenterforNewTechnologiesinLife-ScienceEngineering UniversityofTehranTehranIran SchoolofBiology CollegeofScienceUniversityofTehranTehranIran NanobiomedicineCenterofExcellance UniversityofTehranTehranIran

We present a simple method for direct detection of hydrogen sulfide （H2S） in an aqueous solution. This method represents a novel biosensor based on metalloprotein cytoehrome c （cyt c） with the localized surface plasmon resonance of gold nanoparticles （AuNPs）. For this purpose, we develop a new approach based on attaching chemically-modified cyt e onto AuNPs. Here, by reacting H2S with protein heine center, its conformation changes in the locality of the heine moiety. The eonformational changes occurring in the protein alter the spectral characteristics by changing the dielectric properties of AuNPs. The conformational changes of eyt c induced by the H2S interaction are characterized by the UV-visible absorption spectroscopy and the circular dichroism technique. The limit of the detection and sensitivity of the AuNPs/cyt c biosensor are evaluated by using UV- visible spectroscopy. According to the experiments, it is revealed that H2S can be detected at a concentration of 4.0μM （1.3ppb） by the fabricated AuNPs/cyt c biosensor. In addition, the sensor retains activity and gives reproducible results after storage in 4℃ for 60 d. This simple and cost-effective sensing platform provides a rapid and convenient detection for H2S at concentrations far below the hazardous limit.

关键词： hydrogen sulfide RESEARCH GOLD nanoparticles NANOPARTICLES -- Research METALLOPROTEINS CYTOCHROMES SURFACE plasmon resonance

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hydrogen sulfide regulates abiotic stress tolerance and biotic stress resistance in Arabidopsis

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Journal of Integrative Plant Biology 2015年第7期57卷 628-640页

作者： Haitao Shi Tiantian Ye Ning Han Hongwu Bian Xiaodong Liu Zhulong Chan Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical Gardenthe Chinese Academy of Sciences University of Chinese Academy of Sciences Institute of Genetics State Key Laboratory of Plant Physiology and BiochemistryCollege of Life SciencesZhejiang University College of Agronomy Xinjiang Agricultural University

hydrogen sulfide （H2S） is an important gaseous molecule in various plant developmental processes and plant stress responses. In this study, the transgenic Arabidopsis thaliana plants with modulated expressions of two cysteine desulfhydrases, and exogenous H2S donor （sodium hydrosulfide, NariS） and H2S scavenger （hypotaurine, HT） pre-treated plants were used to dissect the involvement of H2S in plant stress responses. The cysteine desulfhydrases overexpressing plants and NariS pre-treated plants exhibited higher endogenous H2S level and improved abiotic stress tolerance and biotic stress resistance, while cysteine desulfhydrases knockdown plants and HT pre-treated plants displayed lower endogenous H2S level and decreased stress resistance. Moreover, H2S upregulated the transcripts of multiple abiotic and biotic stress-related genes, and inhibited reactive oxygen species （ROS） accumulation. Interest- ingly, MlR393-mediated auxin signaling including MIR393a/b and their target genes （TIR1, AFB1, AFB2, and AFB3） was transcrip-tionally regulated by H2S, and was related with H2S-induced antibacterial resistance. Moreover, H2S regulated 50 carbon metabolites including amino acids, organic acids, sugars, sugar alcohols, and aromatic amines. Taken together, these results indicated that cysteine desulfhydrase and H2S conferred abiotic stress tolerance and biotic stress resistance, via affecting the stress-related gene expressions, ROS metabolism, metabolic homeostasis, and MIR393-targeted auxin receptors.

关键词： Abiotic stress auxin receptor biotic stress cysteine desulfhydrase hydrogen sulfide MIR393

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hydrogen sulfide enhances adult neurogenesis in a mouse model of Parkinson's disease

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Neural Regeneration Research 2021年第7期16卷 1353-1358页

作者： Min Wang Juan-Juan Tang Lin-Xiao Wang Jun Yu Li Zhang Chen Qiao Department of Clinical Pharmacy The Affiliated Hospital of Jiangsu UniversityJiangsu UniversityZhenjiangJiangsu ProvinceChina Department of Geriatrics Affiliated Brain Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina School of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjingJiangsu ProvinceChina Laboratory of Neurological Diseases Department of Neurologythe Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityChangzhouJiangsu ProvinceChina Laboratory of Reproductive Medicine The Affiliated Hospital of Jiangsu UniversityJiangsu UniversityZhenjiangJiangsu ProvinceChina

hydrogen sulfide(H_2S) is regarded to be a protectant against diseases of the central nervous system and cardiovascular ***, the mechanism by which H_2S elicits neuroprotective effects in the progression of Parkinson's disease(PD) remains *** investigate the role of H_2S in delaying the pathological process of PD, we used the most common sodium hydrosulfide(Na HS) as an H_2S donor and established a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid(MPTP/p) in the present *** results show that H_2S reduced neuronal loss during the progression of ***, we found that H_2S exhibited protective effects on dopaminergic ***, H_2S also increased the proliferation of neural stem cells in the subventricular ***, we evaluated whether the neuroprotective effects of H_2S on dopaminergic neurons in PD are dependent on adult nerve regeneration by treating primary adult neural stem cells cultured ex vivo with *** results show that H_2S could prevent nerve injury induced by 1-methyl-4-phenylpyridine, promote the growth of neurospheres, and promote neurogenesis by regulating Akt/glycogen synthase kinase-3β/β-catenin pathways in adult neural stem *** findings confirm that H_2S can increase neurogenesis in an adult mouse model of PD by regulating the Akt/glycogen synthase kinase-3β/β-catenin signaling *** study was approved by the Animal Care and Use Committee of Nanjing Medical University, China(IACUC Approval No.1601153-3).

关键词： factor hydrogen sulfide medical gas neural stem cells neurogenesis neuroprotection Parkinson's disease pathways

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hydrogen sulfide Alleviates Aluminum Toxicity in Germinating Wheat Seedlings

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Journal of Integrative Plant Biology 2010年第6期52卷 556-567页

作者： Hua Zhang Zhu-Qin Tan Lan-Ying Hu Song-Hua Wang Jian-Ping Luo Russell L. Jones School of Biotechnology and Food Engineering Hefei University of Technology Hefei 230009 China Department of Plant and Microbial Biology University of California Berkeley CA 94720 USA Life Science College Anhui Science and Technology University Bengbu 233100 China

Protective role of hydrogen sulfide （H2S） on seed germination and seedling growth was studied in wheat （Triticum） seeds subjected to aluminum （Al3＋） stress. We show that germination and seedling growth of wheat is inhibited by high concentrations of AICI3. At 30 mmol/L AICI3 germination is reduced by about 50% and seedling growth is more dramatically inhibited by this treatment. Pre-incubation of wheat seeds in the H2S donor NaHS alleviates AICI3-induced stress in a dose-dependant manner at an optimal concentration of 0.3 mmol/L. We verified that the role of NaHS in alleviating Al3＋ stress could be attributed to H2S/HS- by showing that the level of endogenous H2S increased following NaHS treatment. Furthermore, other sodium salts containing sulfur were ineffective in alleviating Al3＋ stress. NaHS pretreatment significantly increased the activities of amylases and esterases and sustained much lower levels of MDA and H2O2 in germinating seeds under Al3＋ stress. Moreover, NaHS pretreatment increased the activities of guaiacol peroxidase, ascorbate peroxidase, superoxide dismutase and catalase and decreased that of lipoxygenase. NaHS pretreatment also decreased the uptake of Al3＋ in AICI3-treated seed. Taken together these results suggest that H2S could increase antioxidant capability in wheat seeds leading to the alleviation of Al3＋ stress.

关键词： EFFECT of aluminum on plants hydrogen sulfide WHEAT PLANT nutrients SEEDS -- Growth ESTERASES SODIUM salts PEROXIDASE

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hydrogen sulfide-induced post-translational modification as a potential drug target

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Genes & Diseases 2023年第5期10卷 1870-1882页

作者： Hao-Jie Chen Lei Qian Ke Li Yang-Zhe Qin Jing-Jing Zhou Xin-Ying Ji Dong-Dong Wu School of Basic Medical Sciences Henan UniversityKaifengHenan 475004China Henan International Joint Laboratory for Nuclear Protein Regulation Henan UniversityKaifengHenan 475004China Kaifeng Key Laboratory of Infection and Biological Safety School of Basic Medical SciencesHenan UniversityKaifengHenan 475004China School of Stomatology Henan UniversityKaifengHenan 475004China

hydrogen sulfide (H_(2)S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H_(2)S has been increasing. H_(2)S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H_(2)S in a variety of physiological processes. Current studies have shown that H_(2)S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H_(2)S on physiological and pathological processes, looking forward to providing guidance for subsequent research.

关键词： hydrogen sulfide Modification Phosphorylation S-nitrosylation S-sulfhydration

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hydrogen sulfide May Function Downstream of Nitric Oxide in Ethylene-Induced Stomatal Closure in Vicia faba L.

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Journal of Integrative Agriculture 2012年第10期11卷 1644-1653页

作者： LIU Jing HOU Zhi-hui LIU Guo-hua HOU Li-xia LIU Xin Key Laboratory of Plant Biotechnology in Universities of Shandong Province/College of Life Science Qingdao Agricultural University

Pharmacological, laser scanning confocal microscopic （LSCM）, and spectrophotographic approaches were used to study the roles of hydrogen sulfide （H2S） and nitric oxide （NO） in signaling transduction of stomatal movement in response to ethylene in Viciafaba L. Ethylene treatment resulted in the dose-dependent stomatal closure under light, and this effect was blocked by the inhibitors of H2S biosynthesis in V. faba L. Additionally, ethylene induces H2S generation and increases L-/D-cysteine desulfhydrase （pyridoxalphosphate-dependent enzyme） activity in leaves of V. faba L. Inhibitors of H2S biosynthesis have no effect on the ethylene-induced stomatal closure, NO accumulation, and nitrate reductase （NR） activity in guard cells or leaves of II. faba L. Moreover, the ethylene-induced increase of H2S levels and L-/D- cysteine desulfhydrase activity declined when NO generation was inhibited. Therefore, we conclude that H2S and NO probably are involved in the signal transduction pathway of ethylene-induced stomatal closure. H2S may represent a novel component downstream of NO in the ethylene-induced stomatal movement in V. faba L.

关键词： hydrogen sulfide nitric oxide ethylene stomatal closure Vicia faba L.

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hydrogen sulfide Promotes Wheat Seed Germination and Alleviates Oxidative Damage against Copper Stress

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Journal of Integrative Plant Biology 2008年第12期50卷 1518-1529页

作者： Hua Zhang Lan-Ying Hu Kang-Di Hu Yun-Dong He Song-Hua Wang Jian-Ping Luo School of Biotechnology and Food Engineering Hefei University of Technology Hefei 230009 China Institute of Life Sciences Beijing Normal University Beijing 100875 China Life Science College Anhui Science and Technology University Bengbu 233100 China

With the enhancement of copper （Cu） stress, the germination percentage of wheat seeds decreased gradually. Pretreatment with sodium hydrosulfide （NariS）, hydrogen sulfide （H2S） donor alleviated the inhibitory effect of Cu stress in a dose- dependent manner; whereas little visible symptom was observed in germinating seeds and radicle tips cultured in NariS solutions. It was verified that H2S or HS- rather than other sulfur-containing components derived from NariS attribute to the potential role in promoting seed germination against Cu stress. Further studies showed that NariS could promote amylase and esterase activities, reduce Cu-induced disturbance of plasma membrane integrity in the radicle tips, and sustain lower levels of malondialdehyde and H202 in germinating seeds. Furthermore, NariS pretreatment increased activities of superoxide dismutase and catalase and decreased that of lipoxygenase, but showed no significant effect on ascorbate peroxidase. Alternatively, NariS prevented uptake of Cu and promoted the accumulation of free amino acids in seeds exposed to Cu. In addition, a rapid accumulation of endogenous H2S in seeds was observed at the early stage of germination, and higher level of H2S in NaHS-pretreated seeds. These data indicated that H2S was involved in the mechanism of germinating seeds＇ responses to Cu stress.

关键词： antioxidant enzymes copper stress hydrogen sulfide seed germination wheat (Triticum).

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hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts

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Science China(Life Sciences) 2015年第11期58卷 1126-1134页

作者： ZHANG YouEn WANG JiaNing LI Hua YUAN LiangJun WANG Lei WU Bing GE JunBo Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of Medicine Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Institutes of Biomedical Sciences Fudan University

In heart disease, transforming growth factor-β1 （TGF-β1） converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide （HzS） sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 （10 ng mL-1） for 24 h with or without sodium hydrosul- fide （NariS, 100 μmol L-1, 30 min pretreatment） treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.

关键词： human cardiac fibroblasts hydrogen sulfide transforming growth factor β1 myofibroblasts

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hydrogen sulfide-linked persulfidation of ABI4 controls ABA responses through the transactivation of MAPKKK18 in Arabidopsis

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Molecular Plant 2021年第6期14卷 921-936页

作者： Mingjian Zhou Jing Zhang Jie Shen Heng Zhou Didi Zhao Cecilia Gotor Luis CRomero Ling Fu Zongmin Li Jing Yang Wenbiao Shen Xingxing Yuan Yanjie Xie Laboratory Center of Life Sciences College of Life SciencesNanjing Agricultural UniversityNanjing 210095PR China Instituto de Bioquímica Vegetal y Fotosíntesis Consejo Superior de Investigaciones Científicas y Universidad de SevillaAvenida Américo Vespucio 4941092 SevillaSpain State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences BeijingBeijing Institute of LifeomicsBeijing 102206China Institute of Industrial Crops Jiangsu Academy of Agricultural SciencesNanjing 210014China

hydrogen sulfide(H2S)is a signaling molecule that regulates plant hormone and stress *** phytohormone abscisic acid(ABA)plays an important role in plant adaptation to unfavorable environmental conditions and induces the persulfidation of L-CYSTEINE DESULFHYDRASE1(DES1)and the production of H2S in guard ***,it remains largely unclear how H2S and protein persulfidation participate in the relay of ABA *** this study,we discovered that ABSCISIC ACID INSENSITIVE 4(ABI4)acts downstream of DES1 in the control of ABA responses in ***4 undergoes persulfidation at Cys250 that is triggered in a time-dependent manner by ABA,and loss of DES1 function impairs this ***250 and its persulfidation are essential for ABI4 function in the regulation of plant responses to ABA and the H2S donor NaHS during germination,seedling establishment,and stomatal closure,which are abolished in the ABI4Cys250Ala mutated *** of the ABI4Cys250Ala variant into the abi4 des1 mutant did not rescue its hyposensitivity to ***250 is critical for the binding of ABI4 to its cognate motif in the promoter of Mitogen-Activated Protein Kinase Kinase Kinase 18(MAPKKK18),which propagates the MAPK signaling cascade induced by ***,the DES1-mediated persulfidation of ABI4 enhances the transactivation activity of ABI4 toward MAPKKK18,and ABI4 can bind the DES1 promoter,forming a regulatory *** together,these findings advance our understanding of a post-translational regulatory mechanism and suggest that ABI4 functions as an integrator of ABA and MAPK signals through a process in which DES1-produced H2S persulfidates ABI4 at Cys250.

关键词： hydrogen sulfide persulfidation DES1 ABI4 MAPKXK18 transactivation ABA response

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