2. Academic Validation
  3. DJ-1 activates the Atg5-Atg12-Atg16L1 complex via Sirt1 to influence microglial polarization and alleviate cerebral ischemia/reperfusion-induced inflammatory injury

DJ-1 activates the Atg5-Atg12-Atg16L1 complex via Sirt1 to influence microglial polarization and alleviate cerebral ischemia/reperfusion-induced inflammatory injury

  • Neurochem Int. 2022 Jul;157:105341. doi: 10.1016/j.neuint.2022.105341.
Na Zhao 1,  Yumei Li 2,  Chenglong Wang 3,  Ying Xue 2,  Li Peng 2,  Tingting Wang 2,  Yong Zhao 2,  Ge Xu 4,  Shanshan Yu 5
Affiliations

Affiliations

  • 1 Department of Pathology, College of Basic Medicine, Chongqing Medical University, 400016, Chongqing, PR China; Chengdu Second People's Hospital, 610000, Chengdu, PR China.
  • 2 Department of Pathology, College of Basic Medicine, Chongqing Medical University, 400016, Chongqing, PR China.
  • 3 Department of Pathology, College of Basic Medicine, Chongqing Medical University, 400016, Chongqing, PR China; Department of Pathology, Chongqing Hospital of Traditional Chinese Medicine, 400021, Chongqing, PR China.
  • 4 Institute of Life Sciences, Chongqing Medical University, 400016, Chongqing, PR China.
  • 5 Department of Pathology, College of Basic Medicine, Chongqing Medical University, 400016, Chongqing, PR China. Electronic address: yushanshan2014@cqmu.edu.cn.
PMID: 35429577 DOI: 10.1016/j.neuint.2022.105341
Abstract

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.

Keywords

Atg5-Atg12-Atg16L1; Autophagy; Cerebral I/R injury; DJ-1; Microglial polarization; Sirt1.

Figures
Products
Inhibitors & Agonists
Other Products