title: Cyclophilin B protects SH-SY5Y human neuroblastoma cells against MPP(+)-induced neurotoxicity via JNK pathway.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. PD involves a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyidine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) inhibit the complex I of the mitochondrial electron transport chain, and have been widely used to construct PD models. Cyclophilin B (CypB) is an endoplasmic reticulum protein that binds to cyclosporine A as a cyclophilin family member. CypB has peptidyl-prolyl cis-trans isomerase (PPIase) activity. We investigated the protective effects of overexpressed CypB on MPP+-induced neurocytotoxicity in SH-SY5Y human neuroblastoma cells. Overexpressed CypB decreased MPP(+)-induced oxidative stress through the modulation of antioxidant enzymes including manganese superoxide dismutase and catalase, and prevented neurocytotoxicity via mitogen-activated protein kinase, especially the c-Jun N-terminal kinase pathway. In addition, CypB inhibited the activation of MPP(+)-induced the pro-apoptotic molecules poly (ADP-ribose) polymerase, Bax, and Bcl-2, and attenuated MPP(+)-induced mitochondrial dysfunction. The data suggest that overexpressed CypB protects neuronal cells from MPP+-induced dopaminergic neuronal cell death.
authors: Department of Biomedical Science, Graduate School, Kyung Hee University, Republic of Korea.
authors: Yoojung
authors: Y
authors: Oh
authors: Department of Biomedical Science, Graduate School, Kyung Hee University, Republic of Korea.
authors: Kwon
authors: K
authors: Jeong
authors: Department of Biomedical Science, Graduate School, Kyung Hee University, Republic of Korea.
authors: Kiyoon
authors: K
authors: Kim
authors: Department of Biomedical Science, Graduate School, Kyung Hee University, Republic of Korea.
authors: Young-Seok
authors: YS
authors: Lee
authors: Department of Biomedical Science, Graduate School, Kyung Hee University, Republic of Korea.
authors: Suyun
authors: S
authors: Jeong
authors: Department of Biochemistry and Molecular Biology, Medicine Research Center for Bioreaction of Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Republic of Korea.
authors: Sung Soo
authors: SS
authors: Kim
authors: Department of Biochemistry and Molecular Biology, Medicine Research Center for Bioreaction of Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Republic of Korea.
authors: Kyung-Sik
authors: KS
authors: Yoon
authors: Department of Biochemistry and Molecular Biology, Medicine Research Center for Bioreaction of Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Republic of Korea.
authors: Joohun
authors: J
authors: Ha
authors: Department of Biochemistry and Molecular Biology, Medicine Research Center for Bioreaction of Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Republic of Korea.
authors: Insug
authors: I
authors: Kang
authors: Department of Biochemistry and Molecular Biology, Medicine Research Center for Bioreaction of Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Republic of Korea. Electronic address: wchoe@khu.ac.kr.
authors: Wonchae
authors: W
authors: Choe
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D016923:Cell Death; D045744:Cell Line, Tumor; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; C081786:cyclophilin B; D048031:JNK Mitogen-Activated Protein Kinases; D021983:Cyclophilins; D015655:1-Methyl-4-phenylpyridinium
keywords: Apoptosis; Cyclophilin B; JNK; MPP+; Parkinson's disease