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  • Protective effect of alpha-keto-beta-methyl-n-valeric acid on BV-2 microglia under hypoxia or oxidative stress.

Protective effect of alpha-keto-beta-methyl-n-valeric acid on BV-2 microglia under hypoxia or oxidative stress.

Annals of the New York Academy of Sciences (2005-06-21)
Hsueh-Meei Huang, Hsio-Chung Ou, Huan-Lian Chen, Rolis Chien-Wei Hou, Kee Ching G Jeng
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3-Methyl-2-oxopentanoic acid sodium salt, ≥98%
Sigma-Aldrich
(±)-3-Methyl-2-oxovaleric acid sodium salt