title: Inhibition of mitochondrial fission attenuates Aβ-induced microglia apoptosis.
abstract: Mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of mitochondrial fission protein dynamin-related protein 1 (Drp1), has been reported to display neuroprotective properties in different animal models. In the present study, we investigated the protective effect of mdivi-1 on β-amyloid protein (Aβ)-induced cytotoxicity and its potential mechanisms in BV-2 and primary microglial cells. We found that mitochondrial fission was increased in Aβ treatment and inhibition of mitochondrial fission by mdivi-1 significantly reduced Aβ-induced expression of CD11b (a marker of microglial activation), viability loss and apoptotic rate increase in BV-2 and primary microglial cells. Moreover, we also found that mdivi-1 treatment markedly reversed mitochondrial membrane potential loss, cytochrome c (CytC) release and caspase-3 activation. Altogether, our data suggested that mdivi-1 exerts neuroprotective effects against Aβ-induced microglial apoptosis, and the underlying mechanism may be through inhibiting mitochondrial membrane potential loss, CytC release and suppression of the mitochondrial apoptosis pathway.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: N
authors.initials: N
authors.lastname: Xie
authors.affiliation: Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: yajunlian@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Lian
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D034281:Dynamins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects*; D052999:Quinazolinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D016229:Amyloid beta-Peptides; D039481:CD11b Antigen; D052999:Quinazolinones; D012333:RNA, Messenger; D045304:Cytochromes c; D053148:Caspase 3; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny- ltetrazolium bromide; AD; Alzheimer’s disease; Aβ; BALB; Bagg albino; CytC; DMEM; Drp1; Dulbecco’s modified eagle medium; FBS; GTP; Guanosine triphosphate; HD; Huntington’s disease; MTT; Mdivi-1; PBS; PD; Parkinson’s disease; RT-PCR; Reverse transcription-PCR; Rh-123; TUNEL; apoptosis; cytochrome c; dynamin-related protein 1; fetal bovine serum; mdivi-1; microglia; mitochondrial division inhibitor 1; phosphate buffered saline; rhodamine 123; terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling; β-amyloid; β-amyloid protein