title: The regulation of rotenone-induced inflammatory factor production by ATP-sensitive potassium channel expressed in BV-2 cells.
abstract: Our previous studies have demonstrated that activating ATP-sensitive potassium channel (K(ATP) channel), not only improved Parkinsonian behavior and neurochemical symptoms, but also reduced iNOS activity and mRNA levels in striatum and nigra of rotenone rat model of Parkinson's disease (PD). In this study, it was first shown that the subunits of K(ATP) channels are expressed in BV-2 cells, and then it was investigated whether K(ATP) channel was involved in regulating inflammatory factor production from BV-2 cells activated by rotenone. It was found that K(ATP) channel was expressed in BV-2 cell and formed by the combination of Kir 6.1 and SUR 2A/2B. K(ATP) channel openers (KCOs) including pinacidil, diazoxide and iptakalim (Ipt) exerted beneficial effects on rotenone-induced morphological alterations of BV-2 cells, decreased tumor necrosis factor alpha (TNF-alpha) production and the expression and activity of inducible isoform of nitric oxide synthase (iNOS). Either glibenclamide or 5-hydroxydecanoate acid (a selective mitochondrial K(ATP) channel blocker) could abolish the effects of KCOs, suggesting that K(ATP) channels, especially mitochondrial ATP-sensitive potassium channels (mitoK(ATP) channels), played a crucial role in preventing the activation of BV-2 cells, and subsequently the production of a variety of proinflammatory factors. Therefore, activation of K(ATP) channel might be a new therapeutic strategy for treating neuroinflammatory and neurodegenerative disorders.
authors.affiliation: Laboratory of Neuropharmacology, Department of Anatomy, Histology & Pharmacology, Institute of Neurosciences, Nanjing Medical University, Jiangsu, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Jia-Yong
authors.initials: JY
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Sun
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yao
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D003652:Decanoic Acids / Q000494:pharmacology; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011437:Propylamines / Q000494:pharmacology; D011955:Receptors, Drug; D012402:Rotenone / Q000494:pharmacology*; D064233:Sulfonylurea Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D003652:Decanoic Acids; D006880:Hydroxy Acids; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011437:Propylamines; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014409:Tumor Necrosis Factor-alpha; D012402:Rotenone; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D052247:Nitric Oxide Synthase Type II; D005905:Glyburide