title: The Short Isoform of DNAJB6 Protects against 1-Methyl-4-phenylpridinium Ion-Induced Apoptosis in LN18 Cells via Inhibiting Both ROS Formation and Mitochondrial Membrane Potential Loss.
abstract: In a previous study, we found that the short isoform of DNAJB6 (DNAJB6(S)) had been decreased in the striatum of a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). DNAJB6, one of the heat shock proteins, has been implicated in the pathogenesis of PD. In this study, we explored the cytoprotective effect of DNAJB6(S) against 1-methyl-4-phenylpyridinium ion- (MPP+-) induced apoptosis and the underlying molecular mechanisms in cultured LN18 cells from astrocytic tumors. We observed that MPP+significantly reduced the cell viability and induced apoptosis in LN18 glioblastoma cells. DNAJB6(S) protected LN18 cells against MPP+-induced apoptosis not only by suppressing Bax cleavage but also by inhibiting a series of apoptotic events including loss of mitochondrial membrane potential, increase in intracellular reactive oxygen species, and activation of caspase-9. These observations suggest that the cytoprotective effects of DNAJB6(S) may be mediated, at least in part, by the mitochondrial pathway of apoptosis.
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Meridian & Acupoint, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yeon-Mi
authors.initials: YM
authors.lastname: Hong
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Meridian & Acupoint, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Neurodegenerative Diseases, Ilsong Institute of Life Science, Hallym University, Anyang, Republic of Korea.
authors.forename: Yeong-Gon
authors.initials: YG
authors.lastname: Choi
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Meridian & Acupoint, College of Korean Medicine, Sangji University, Wonju, Republic of Korea.
authors.forename: Sujung
authors.identifier: 0000-0001-9883-6153
authors.initials: S
authors.lastname: Yeo
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Jin
authors.affiliation: Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Sae-Won
authors.identifier: 0000-0002-2503-1204
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Biology, Pacific Union College, Angwin, CA 94508, USA.
authors.forename: Backil
authors.initials: B
authors.lastname: Sung
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Meridian & Acupoint, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sook-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Meridian & Acupoint, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Jung
authors.affiliation: Research Group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea; Department of Meridian & Acupoint, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sabina
authors.identifier: 0000-0003-0509-6681
authors.initials: S
authors.lastname: Lim
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D019610:Cytoprotection; D004789:Enzyme Activation; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C485565:DNAJB6 protein, human; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D053453:Caspase 9; D015655:1-Methyl-4-phenylpyridinium