Ethyl pyruvate protects PC12 cells from oxygen-glucose deprivation: A potential role in ischemic cerebrovascular disease

Biomed Pharmacother. 2017 Aug;92:168-174. doi: 10.1016/j.biopha.2017.05.067. Epub 2017 May 21.

Abstract

The protective potential of ethyl pyruvate (EP) on neuron has been investigated previously. This study was intended to investigate the effects of EP on the severity of oxygen-glucose deprivation (OGD)-induced injury in neural-like PC12 cells. PC12 cells were exposed to OGD condition with or without EP treatment. Then, cell viability, apoptosis, and the expressions of neurotrophic factors were detected. Further, Sprague-Dawley rats were intravenously administered with 5mg/kg EP for 14 days post-middle cerebral artery occlusion (MCAO). The effects of EP on the infarct volumes and neurological functions of MCAO rats were then assessed. Result showed that EP alleviated OGD-diminished cells viability, OGD-induced apoptosis, and OGD-reduced expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and Nestin in PC-12 cells. EP blocked OGD-activated the Notch1 and nuclear factor Kappa B (NF-κB) signaling pathways in PC12 cells. Besides, in vivo data demonstrated that EP treatment decreased infarct volume and mNSS score, and increased the time spent on the rota-rod apparatus of MCAO rats. To conclude, EP protected neural-like PC12 cells from cerebral ischemia-reperfusion injury by suppressing apoptosis and promoting neural restoration. Notch1 and NF-κB pathway might implicated in the functions of EP on neuron.

Keywords: Apoptosis; Ethyl pyruvate; Ischemic cerebrovascular disease; Middle cerebral artery occlusion (MCAO); Notch1/NF-κB pathway; Oxygen-glucose deprivation.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain-Derived Neurotrophic Factor / agonists
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression Regulation / drug effects
  • Infarction, Middle Cerebral Artery / physiopathology
  • Injections, Intravenous
  • Male
  • Nerve Growth Factor / agonists
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin / agonists
  • Nestin / genetics
  • Nestin / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Pyruvates / administration & dosage
  • Pyruvates / pharmacology
  • Pyruvates / therapeutic use*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Specific Pathogen-Free Organisms

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Tissue Proteins
  • Nestin
  • Neuroprotective Agents
  • Pyruvates
  • ethyl pyruvate
  • Nerve Growth Factor