MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway

Neurochem Int. 2024 Nov:180:105881. doi: 10.1016/j.neuint.2024.105881. Epub 2024 Oct 13.

Abstract

Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo, MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.

Keywords: Acupuncture; Apoptosis; Ischemic stroke; MRPL41; p53 pathway.

MeSH terms

  • Acupuncture Therapy* / methods
  • Animals
  • Apoptosis* / physiology
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Ischemic Stroke* / metabolism
  • Ischemic Stroke* / pathology
  • Male
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Neurons* / metabolism
  • Neurons* / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Ribosomal Proteins
  • Mitochondrial Proteins