DJ-1 activates the Atg5-Atg12-Atg16L1 complex via Sirt1 to influence microglial polarization and alleviate cerebral ischemia/reperfusion-induced inflammatory injury.
Neurochemistry international(2022)
摘要
BACKGROUND:After cerebral ischemia/reperfusion (I/R) injury, activated microglia can be polarized towards different phenotypes (the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype) to regulate neuroinflammation. Our previous research showed that DJ-1 has anti-inflammatory effects in cerebral I/R. Here, we examined whether the neuroprotective effect of DJ-1 is related to the autophagy-associated Atg5-Atg12-Atg161L1 complex and whether Sirt1 is involved in the influence of DJ-1 by mediating microglial polarization and ameliorating cerebral I/R injury.
METHODS:To answer these questions, we adopted the middle cerebral artery occlusion/reperfusion (MCAO/R) model to simulate I/R injury, knocked down the expression of DJ-1 with siRNA, and used the chemical inhibitor EX-527 to inhibit the expression of Sirt1. Related indexes were evaluated by Western blotting, immunoprecipitation and transmission electron microscopy.
RESULTS:Interference with DJ-1 promotes the polarization of microglia from the anti-inflammatory phenotype to the proinflammatory phenotype. Addition of a Sirt1 inhibitor following DJ-1 interference enhances the effect of DJ-1 interference on microglial polarization, decreases the level of the Atg5-Atg12-Atg16L1 complex, and inhibits autophagy.
CONCLUSION:These results suggest that DJ-1 regulates the polarization of microglia during cerebral I/R injury, possibly by activating the Atg5-Atg12-Atg16L1 complex through Sirt1 to promote autophagy.
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关键词
DJ-1,Microglial polarization,Sirt1,Autophagy,Cerebral I,R injury
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