title: Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating GRP78 in SH-SY5Y cells.
abstract: Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects dopaminergic neurons from damage. In this study, we used MTT, immunohistochemistry, and TUNEL staining to investigate the protective effect of MANF in SH-SY5Y cells treated with 6-OHDA or overexpressed α-synuclein. Cleaved caspase-3 levels significantly increased in cells treated with 6-OHDA or overexpressed α-synuclein. 6-OHDA or α-synuclein overexpression that induced cleaved caspase-3 levels to increase was reduced by MANF treatment. In addition, MANF treatment upregulated GRP78 expressions in cells treated with 6-OHDA or overexpressed α-synuclein, and RNAi knockdown for GRP78 could block the MANF induced cell survival from 6-OHDA treatment. Furthermore, GRP78 overexpression inhibited 6-OHDA-induced apoptosis. Our data suggest that MANF inhibits apoptosis induced by 6-OHDA and overexpressed α-synuclein in SH-SY5Y cells via upregulating GRP78 in the transcriptional pattern.
authors.affiliation: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
authors.forename: Changyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gu
authors.affiliation: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu, 215101, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.|Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu, 215101, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.|Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu, 215101, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.|Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu, 215101, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, China.
authors.forename: Lingjing
authors.initials: L
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009414:Nerve Growth Factors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects; D051844:alpha-Synuclein / Q000096:biosynthesis
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C099695:MANF protein, human; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D051844:alpha-Synuclein; D016627:Oxidopamine; D053148:Caspase 3
keywords: GRP78; MANF; Parkinson's disease; SH-SY5Y