Downregulation of mitochondrial pyruvate carrier 2 aggravates neuronal injury in the cortex following cerebral ischemia in rat

Brain Res Bull. 2022 Jul;185:193-202. doi: 10.1016/j.brainresbull.2022.05.007. Epub 2022 May 14.

Abstract

Cerebral ischemia is one of the most common disabling and lethal diseases worldwide, but its underlying mechanisms remain unclear. Mitochondrial pyruvate carrier 2 (MPC2), a subunit of MPC complex, plays pivotal roles in coordinating glycolytic and mitochondrial activities. In the present study, the expression of MPC2 was significantly reduced in the ischemic cerebral cortex of rats at 24 h after bilateral internal carotid artery occlusion (BICAO), and in the cortical neurons after 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation treatment. After MPC2 gene knockdown, the number and expression of neurons were remarkably decreased in the ischemic cerebral cortex of BICAO rats and OGD-treated neurons. UK5099 significantly reduced the number, expression and viability of OGD-treated neurons, and resulted in a significant decrease in length of neurite. Using RNA-sequencing (RNA-seq) technique, we further identified MPC2-related differential genes in the ischemic cerebral cortex of BICAO rats. In conclusion, our results suggested that the decrease in MPC2 expression aggravated ischemic injury, and MPC2-related genes might be a novel therapeutic target for cerebral ischemia.

Keywords: Bilateral internal carotid artery occlusion (BICAO); Mitochondrial pyruvate carrier 2 (MPC2); Neuron; RNA-sequencing (RNA-seq) technique.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Brain Ischemia* / metabolism
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Cerebral Infarction
  • Down-Regulation
  • Glucose / metabolism
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism
  • Neurons / metabolism
  • Rats
  • Reperfusion Injury* / metabolism

Substances

  • Monocarboxylic Acid Transporters
  • Glucose