title: Molecular effects of activated BV-2 microglia by mitochondrial toxin 1-methyl-4-phenylpyridinium.
abstract: Microglia plays an important role in inflammation-mediated neurodegeneration. Compelling evidence supports the hypothesis that microglial activation contributes to the pathogenesis of various neurodegenerative diseases. However, little is known about the molecular outcome of activated microglia. In this report, we investigate the molecular consequences of MPP(+) toxin-induced activated BV-2 microglia. Intoxication of specific mitochondrial toxin methyl-4-phenylpyridinium iodide ion (MPP(+)) to BV-2 cells induced significant mitochondrial dysfunction and increased the reactive oxygen species generation, caspase-3 activation, and poly ADP ribose polymerase proteolysis. Further, MAC-1 immunostaining in the midbrain of mice revealed a decrease in activated microglia at day 4 after intoxication with MPP(+). From this study, it was confirmed that BV-2 microglia respond to the mitochondrial toxin MPP(+) which may lead to apoptotic cell death. Understanding of the mechanistic basis of apoptotic elimination of activated microglia may help to develop new strategies for the treatment of neurodegenerative diseases.
authors.affiliation: Research Institute of Inflammatory Diseases, Department of Biotechnology, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Meihua
authors.initials: M
authors.lastname: Jin
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Kim
authors.forename: Sushruta
authors.initials: S
authors.lastname: Koppula
authors.forename: In Su
authors.initials: IS
authors.lastname: Kim
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Hemant
authors.initials: H
authors.lastname: Kumar
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006540:Herbicides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015655:1-Methyl-4-phenylpyridinium; D017304:Annexin A5; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053148:Caspase 3; D006540:Herbicides; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C499321:Parp1 protein, mouse