Protective effect of α-keto-β-methyl-n-valeric acid on BV-2 microglia under hypoxia or oxidative stress
Protective effect of α-keto-β-methyl-n-valeric acid on BV-2 microglia under hypoxia or oxidative stress
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DOI：
10.1196/annals.1338.049
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Jeng, KCG
中科院分区：
文献类型：
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作者：
Huang, HM;Ou, HC;Jeng, KCG
α-酮戊二酸脱氢酶复合物（KGDHC）是三羧酸循环中的线粒体酶。α-酮-β-甲基-n-戊酸（KMV）对KGDHC活性的抑制与神经元死亡相关。然而，KMV在小胶质细胞中的作用尚不清楚。因此，我们研究了KMV对暴露于缺氧或氧化应激的BV-2小胶质细胞的影响。结果表明，KMV（1-20 mM）可提高细胞在缺氧条件下的存活率。KMV剂量依赖性地减少低氧BV-2细胞的ROS和LDH释放。KMV还减少ROS的产生，提高细胞活力下H2 O2，但不能降低SIN-1和硝普钠（SNP）的毒性。KMV还降低了应激下caspase-3和-9的活化。这些结果表明，KMV保护BV-2细胞免受应激，并通过抑制KDGHC减少ROS产生来起作用。
The a-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.