Malate-aspartate shuttle inhibitor aminooxyacetic acid blocks lipopolysaccharides-induced activation of BV2 microglia.

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Malate-aspartate shuttle inhibitor aminooxyacetic acid blocks lipopolysaccharides-induced activation of BV2 microglia.

Int J Physiol Pathophysiol Pharmacol. 2017;9(2):58-63

Authors: Shang W, Wei X, Ying W

Abstract
NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, mediate the transfer of the reducing equivalents of cytosolic NADH into mitochondria. In our current study, we used BV2 microglia as a cellular model to determine the roles of NADH shuttles in lipopolysaccharides (LPS)-induced microglial activation. We found that aminooxyacetic acid (AOAA), a widely used MAS inhibitor, significantly attenuated LPS-induced increases in the levels of nitric oxide-a hallmarker of microglial activation. Our Western Blot assays also showed that AOAA blocked the LPS-induced increases in the protein levels of iNOS, TNF-α and COX-2. Furthermore, we found that AOAA decreased LPS-induced nuclear translocation of NF-κB. Collectively, our study has suggested that AOAA may be a new agent for inhibiting microglial activation. Our study has also suggested that MAS may be a novel target for modulating microglial activation under pathological conditions.

PMID: 28533892 [PubMed - in process]

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