title: Protective effect of alpha-keto-beta-methyl-n-valeric acid on BV-2 microglia under hypoxia or oxidative stress.
abstract: The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme in the TCA cycle. Inhibition of KGDHC activity by alpha-keto-beta-methyl-n-valeric acid (KMV) is associated with neuron death. However, the effect of KMV in microglia is unclear. Therefore, we investigated the effect of KMV on BV-2 microglial cells exposed to hypoxia or oxidative stress. The results showed that KMV (1-20 mM) enhanced the cell viability under hypoxia. KMV dose-dependently reduced ROS and LDH releases from hypoxic BV-2 cells. KMV also reduced ROS production and enhanced the cell viability under H2O2 but failed to reduce the SIN-1 and sodium nitroprusside (SNP) toxicity. KMV also reduced caspase-3 and -9 activation under stress. These results suggest that KMV protects BV-2 cells from stress and acts by reducing ROS production through inhibition of KDGHC.
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
authors.forename: Hsueh-Meei
authors.initials: HM
authors.lastname: Huang
authors.forename: Hsio-Chung
authors.initials: HC
authors.lastname: Ou
authors.forename: Huan-Lian
authors.initials: HL
authors.lastname: Chen
authors.forename: Rolis Chien-Wei
authors.initials: RC
authors.lastname: Hou
authors.forename: Kee Ching G
authors.initials: KC
authors.lastname: Jeng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007651:Keto Acids / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007651:Keto Acids; D017382:Reactive Oxygen Species; C016211:alpha-keto-beta-methylvaleric acid; D006861:Hydrogen Peroxide