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

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-? and COX-2. Furthermore, we found that AOAA decreased LPS-induced nuclear translocation of NF-?B. 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.

SUBMITTER: Shang W 

PROVIDER: S-EPMC5435673 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature