title: Hydrogen sulfide inhibits MPP+-induced aldehyde stress and endoplasmic reticulum stress in PC12 cells: involving upregulation of BDNF.
abstract: We have previously demonstrated the protective action of hydrogen sulfide (H2S) in 1-Methy-4-Phenylpyridinium Ion (MPP+)-induced neurotoxicity. However, the exact mechanisms of this protection remain largely unknown. Aldehyde stress and endoplasmic reticulum (ER) stress play significant roles in the neurotoxicity of MPP+. Brain derived neurotrophic factor (BDNF) is an important endogenous neuroprotectant. Therefore, we speculated that the protection of H2S against MPP+neurotoxicity results from inhibiting MPP+-induced aldehyde stress and ER stress via upregulation of BDNF. In the present study, we found that NaHS, a donor of H2S, inhibited MPP+-induced aldehyde stress (the accumulations of the intracellular 4-HNE and MDA) and ER stress (the increases in the expressions of GRP78 and Cleaved-caspase-12) in PC12 cells and upregulated the BDNF expression in MPP+-exposed PC12 cells. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, not only markedly reversed the inhibitiory role of NaHS in MPP+-induced aldehyde stress and ER stress, but also ablated the protection of NaHS against MPP+-induced neurotoxicity. These data demonstrated that the protective role of H2S against MPP+-induced neurotoxicity by inhibiting aldehyde stress and ER stress, which is involved in upregulation of BDNF.
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Medical College, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China. Electronic address: zouw415@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, Hunan, PR China; Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China; Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, Hengyang 421001, Hunan, PR China. Electronic address: tangxq-usc@qq.com.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D053454:Caspase 12 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D026121:Indole Alkaloids / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000447:Aldehydes; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D026121:Indole Alkaloids; D018696:Neuroprotective Agents; C049985:staurosporine aglycone; D053454:Caspase 12; D015655:1-Methyl-4-phenylpyridinium; D006862:Hydrogen Sulfide
keywords: 1-Methy-4-Phenylpyridinium Ion; Aldehyde stress; Brain derived neurotrophic factor; Endoplasmic reticulum stress; Hydrogen sulfide