Protective Effect of α‐Keto‐β‐Methyl‐n‐Valeric Acid on BV‐2 Microglia under Hypoxia or Oxidative Stress

A bstract : The α‐ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme in the TCA cycle. Inhibition of KGDHC activity by α‐keto‐β‐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 H 2 O 2 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.