Propofol alleviates hypoxia-induced nerve injury in PC-12 cells by up-regulation of microRNA-153

BMC Anesthesiol. 2018 Dec 22;18(1):197. doi: 10.1186/s12871-018-0660-z.

Abstract

Background: Although the neuroprotective role of propofol has been identified recently, the regulatory mechanism associated with microRNAs (miRNAs/miRs) in neuronal cells remains to be poorly understood. We aimed to explore the regulatory mechanism of propofol in hypoxia-injured rat pheochromocytoma (PC-12) cells.

Methods: PC-12 cells were exposed to hypoxia, and cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry assay/Western blot analysis, respectively. Effects of propofol on hypoxia-injured cells were measured, and the expression of miR-153 was determined by stem-loop RT-PCR. After that, whether propofol affected PC-12 cells under hypoxia via miR-153 was verified, and the downstream protein of miR-153 as well as the involved signaling cascade was finally explored.

Results: Hypoxia-induced decrease of cell viability and increase of apoptosis were attenuated by propofol. Then, we found hypoxia exposure up-regulated miR-153 expression, and the level of miR-153 was further elevated by propofol in hypoxia-injured PC-12 cells. Following experiments showed miR-153 inhibition reversed the effects of propofol on hypoxia-treated PC-12 cells. Afterwards, we found BTG3 expression was negatively regulated by miR-153 expression, and BTG3 overexpression inhibited the mTOR pathway and AMPK activation. Besides, hypoxia inhibited the mTOR pathway and AMPK, and these inhibitory effects could be attenuated by propofol.

Conclusion: Propofol protected hypoxia-injured PC-12 cells through miR-153-mediataed down-regulation of BTG3. BTG3 could inhibit the mTOR pathway and AMPK activation.

Keywords: BTG3; Hypoxia injury; PC-12 cells; Propofol; mTOR/AMPK; miR-153.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Apoptosis / drug effects
  • Cell Hypoxia / drug effects*
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Flow Cytometry
  • MicroRNAs / genetics*
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Propofol / pharmacology*
  • Proteins / genetics
  • Rats
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation / drug effects

Substances

  • Btg3 protein, rat
  • MIRN153 microRNA, rat
  • MicroRNAs
  • Neuroprotective Agents
  • Proteins
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Propofol