title: Opening of microglial K(ATP) channels inhibits rotenone-induced neuroinflammation.
abstract: As activated microglia (MG) is an early sign that often precedes and triggers neuronal death, inhibition of microglial activation and reduction of subsequent neurotoxicity may offer therapeutic benefit. The present study demonstrates that rat primary cultured MG expressed Kir6.1 and SUR2 subunits of K(ATP) channel, which was identical to that expressed in BV-2 microglial cell line. The classic K(ATP) channel opener pinacidil and selective mitochondrial K(ATP) (mito-K(ATP)) channel opener diazoxide prevented rotenone-induced microglial activation and production of pro-inflammatory factors (tumour necrosis factor[TNF]-alpha and prostaglandin E(2)[PGE(2)]). And the effects of pinacidil and diazoxide were reversed by mito-K(ATP) blocker 5-hydroxydecanoate (5-HD), indicating that mito-K(ATP) channels participate in the regulation of microglial activation. Moreover, the underlying mechanisms involved the stabilization of mitochodrial membrane potential and inhibition of p38/c-Jun-N-terminal kinase (JNK) activation in microglia. Furthermore, the in vivo study confirmed that diazoxide exhibited neuroprotective effects against rotenone along with the inhibition of microglial activation and neuroinflammation. Thus, microglial mito-K(ATP) channel might be a novel prospective target for the treatment of neuroinflammation-related degenerative disorders such as Parkinson's disease.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Anatomy Histology, Pharmacology Nanjing Medical University Nanjing, Jiangsu, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yao
authors.forename: Jia-Yong
authors.initials: JY
authors.lastname: Wu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D054086:KATP Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D054086:KATP Channels; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D012402:Rotenone; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D003981:Diazoxide