Knocking Down Peroxiredoxin 6 Aggravates Cerebral Ischemia-Reperfusion Injury by Enhancing Mitophagy

Neuroscience. 2022 Feb 1:482:30-42. doi: 10.1016/j.neuroscience.2021.11.043. Epub 2021 Dec 1.

Abstract

Cerebral ischemia-reperfusion injury (IRI) is caused by reperfusion following ischemia. Mitophagy is closely related to cerebral IRI. Mitophagy disorder or excess may be harmful and lead to neuronal apoptosis. Peroxiredoxin 6 (PRDX6) is an antioxidant protein and plays an important role in ischemic stroke. However, the relationship between PRDX6 and mitophagy is not clear at present. In order to explore and solve this problem. We have established a middle cerebral artery occlusion (MCAO) model of cerebral ischemia-reperfusion in SD rats and knockdown PRDX6 and PINK1 with lentivirus. Knocking down PRDX6 led to further aggravation of cerebral IRI. Our research found that knockdown PRDX6 increased the expression of mitophagy-related and apoptosis-related proteins. Knocking down PINK1 relieved mitophagy and apoptosis caused by knocking down PRDX6. In conclusion, knockdown of PRDX6 could aggravate cerebral IRI by enhancing PINK1/PARKIN pathway mediated mitophagy, and this effect could increase neuronal apoptosis.

Keywords: apoptosis; cerebral ischemia–reperfusion injury; mitophagy; peroxiredoxin 6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mitochondria / metabolism
  • Mitophagy*
  • Peroxiredoxin VI / genetics
  • Peroxiredoxin VI / metabolism
  • Protein Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Peroxiredoxin VI
  • Prdx6 protein, rat
  • Ubiquitin-Protein Ligases
  • Protein Kinases