Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction

Ai Ling Cui, Ying Hua Zhang, Jian Zhong Li, Tianbin Song, Xue Min Liu, Hui Wang, Ce Zhang, Guo Lin Ma, Hui Zhang, Kefeng Li

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

N-methyl-D-aspartate (NDMA) receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer’s disease (AD) and Parkinson’s disease. However, no effective treatments for the same have been developed so far. Humanin (HN) is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction. In this study, excitatory toxicity was induced by NMDA, which binds the NMDA receptor in primarily cultured rat cortical neurons. We found that NMDA (100 μmol/L) dramatically induced the decrease of cell viability and caused mitochondrial dysfunction. Pretreatment of the neurons with HN (1 µmol/L) led to significant increases of mitochondrial succinate dehydrogenase (SDH) activity and membrane potential. In addition, HN pretreatment significantly reduced the excessive production of both reactive oxygen species (ROS) and nitric oxide (NO). Thus, HN could attenuate the excitotoxicity caused by the overactivation of the NMDA receptor through the alleviation of mitochondrial dysfunction.

Original languageEnglish
Pages (from-to)1243-1253
Number of pages11
JournalDrug Design, Development and Therapy
Volume11
DOIs
Publication statusPublished - 18 Apr 2017
Externally publishedYes

Keywords

  • Alleviation
  • Humanin
  • Mitochondrial dysfunction
  • NMDA-induced toxicity

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