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: Hsueh-Meei Huang, Hsio-Chung Ou, Huan-Lian Chen, Rolis Chien-Wei Hou, Kee Ching G Jeng
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1042 Pg. 272-8 (May 2005) ISSN: 0077-8923 [Print] United States
• PMID: 15965072 (Publication Type: Journal Article)

Chemical References

• Keto Acids
• Reactive Oxygen Species
• alpha-keto-beta-methylvaleric acid
• Hydrogen Peroxide

Topics

• Apoptosis (drug effects)
• Cell Hypoxia (drug effects, physiology)
• Cell Line
• Cytoprotection (drug effects)
• Humans
• Hydrogen Peroxide (pharmacology)
• Keto Acids (pharmacology)
• Microglia (cytology, drug effects, metabolism)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)