2. Academic Validation
  3. Platonin protects against cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasomes via BNIP3/LC3 signaling mediated autophagy

Platonin protects against cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasomes via BNIP3/LC3 signaling mediated autophagy

  • Brain Res Bull. 2022 Mar;180:12-23. doi: 10.1016/j.brainresbull.2021.12.008.
Jing Luo 1,  Junyi Tan 2,  Ning Jiang 1,  Changhong Yang 3,  Jialei Chen 2,  Jing Zhao 4,  Lingyu Li 5,  Yong Zhao 6
Affiliations

Affiliations

  • 1 Department of Pathology, Chongqing Medical University, Chongqing 400016, China.
  • 2 Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.
  • 3 Department of Bioinformatics, Chongqing Medical University, Chongqing 400016, China.
  • 4 Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
  • 5 Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
  • 6 Department of Pathology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
PMID: 34953929 DOI: 10.1016/j.brainresbull.2021.12.008
Abstract

Studies have found that Platonin has neuroprotective effect, but its molecular mechanism needs further study. We found that at the early stage of cerebral ischemia/reperfusion injury, Platonin treatment significantly reduced cerebral infarct lesions, improved neurological scores, and exerted neuroprotective effects. Our group has shown that NLRP3 inflammasomes activation is required to mediate neuronal injury during cerebral ischemia /reperfusion injury. The brain protective effect of Platonin is related to its ability to effectively regulate Autophagy and NLRP3 inflammasomes-derived inflammation. Platonin treatment effectively induced Autophagy (LC3II/I, p62) and reduced NLRP3 inflammasomes activation(NLRP3, cleaved-IL-1β，cleaved-IL-18, cleaved-caspase1). However, 3-MA (15 mg/kg) treatment downregulated the inhibitory effect of Platonin on NLRP3 inflammasomes. We also studied the location of BNIP3 in Platonin-mediated neuroprotection and found that Platonin induced the expression of autophagic protein BNIP3 and enhanced the co-immunoprecipitation of BNIP3 with LC3, and double-labeled immunofluorescence also showed enhanced co-localization of BNIP3 with LC3. Finally, si-BNIP3 transfection attenuated the co localization of BNIP3 with LC3, decreased the Autophagy activity to a certain extent and blocked the inhibition of NLRP3 inflammasomes-derived inflammation by Platonin. This study demonstrated that Platonin may play a neuroprotection role in cerebral I / R injury by inhibiting NLRP3 inflammasomes activation through upregulating Autophagy via BNIP3 / LC3 pathway.

Keywords

Autophagy; BNIP3; Cerebral I/R injury; Inflammation; LC3; NLRP3 inflammasomes; Neuroprotection; Platonin.

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