ETS-domain containing protein (Elk1) suppression protects cortical neurons against oxygen-glucose deprivation injury

Exp Cell Res. 2018 Oct 1;371(1):42-49. doi: 10.1016/j.yexcr.2018.07.038. Epub 2018 Jul 24.

Abstract

ETS-domain containing protein (Elk1), which is a transcription factor, is reported to be closely related to the apoptosis of primary neurons and could be activated by hypoxia in human microvascular endothelial cells. In this study, we aimed to investigate the role of Elk1 in cortical neurons under oxygen-glucose deprivation (OGD) conditions. The OGD model of cortical neurons was established the anoxia/hypoglycemia-induced injury and the in vivo model was established by middle cerebral artery occlusion (MCAO). Elk1 mRNA and protein expression was significantly up-regulated in neurons exposed to OGD for 24 h, and mRNA expression was also markedly increased in cerebral cortex of rats with MCAO after 10 days. The knockdown of Elk1 in neurons without OGD obviously constrained Fra-1 and promoted Nrf2 expression. Also, Elk1 inhibition suppressed neuronal apoptosis, caspase-3 activity, LDH leakage, and MDA and SOD contents, while it increased cell viability in the neurons with OGD. The overexpression of Fra-1 showed a reverse effect on caspase-3 activity, cell viability and SOD contents in neurons under OGD conditions compared with Elk1 knockdown. Thus, Elk1 inhibition has a protective effect on neurons against OGD-induced injury.

Keywords: Elk1; Fra-1; Inhibition; Nrf2; OGD.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebrovascular Disorders / surgery
  • Fetus
  • Gene Expression Regulation
  • Glucose / deficiency
  • Glucose / pharmacology*
  • Hypoxia / genetics*
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Male
  • Middle Cerebral Artery / surgery
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxygen / pharmacology*
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • ets-Domain Protein Elk-1 / antagonists & inhibitors
  • ets-Domain Protein Elk-1 / genetics*
  • ets-Domain Protein Elk-1 / metabolism

Substances

  • Elk1 protein, rat
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Proto-Oncogene Proteins c-fos
  • RNA, Small Interfering
  • ets-Domain Protein Elk-1
  • fos-related antigen 1
  • Superoxide Dismutase
  • Casp3 protein, rat
  • Caspase 3
  • Glucose
  • Oxygen