Dexmedetomidine exerts neuroprotective effects during high glucose-induced neural injury by inhibiting miR-125b

Biosci Rep. 2020 Jun 26;40(6):BSR20200394. doi: 10.1042/BSR20200394.

Abstract

Diabetic neuropathy (DNP) is the most common complication of diabetes mellitus affecting approximately 50% of diabetes patients. Studying the effect of potential drugs with antioxidant properties and minimal toxicities on neural cells may lead to the development of new and safe pharmacotherapy. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, is a clinically used sedative also known to have neural protection effect. In the present study, we aimed to investigate the protective role of DEX in high glucose (HG)-induced neural injury and its potential miRNA-related mechanisms. Our results showed that DEX exerted neuroprotective effects during high glucose-induced damage to PC12 cells in a dose-dependent manner. DEX restored cell viability and repressed LDH, Caspase-3 activity, ROS production, and cell apoptosis in HG-treated PC12 cells. MiR-125b-5p was significantly up-regulated in PC12 cells upon HG treatment and it was demonstrated as an target for DEX. The neuroprotective effects of DEX on HG-induced cellular injury were reversed through miR-125b-5p overexpression, and vitamin D receptor (VDR) is a direct targeted of the miR-125b-5p. Together, our results indicate that DEX displays neuroprotective effects on PC-12 cells under high glucose through regulating miR-125b-5p/VDR axis. Our findings might raise the possibility of potential therapeutic application of DEX for managing diabetic neuropathy neural injuries.

Keywords: Dexmedetomidine; diabetic neuropathy; high glucose; miR-125b-5p; vitamin D receptor.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Dexmedetomidine / pharmacology*
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / genetics
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / pathology
  • Glucose / toxicity*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / metabolism
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Signal Transduction
  • Up-Regulation

Substances

  • MIRN125 microRNA, rat
  • MicroRNAs
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Receptors, Calcitriol
  • Dexmedetomidine
  • Glucose