Alcohol inhibits the proliferation of Neuro2a cells via promoting the asymmetric cell division through down-regulation of the expression of centrosome protein-J

Toxicol Lett. 2018 Sep 15:294:177-183. doi: 10.1016/j.toxlet.2018.05.021. Epub 2018 May 17.

Abstract

Alcohol can decrease cell proliferation in neural cells. The proliferation of neural cells can be inhibited by the asymmetric division of neural progenitor cells. However, whether alcohol inhibits cell proliferation through inducing cell asymmetric division is not yet clear. Here, we reported that the percentage of asymmetric division was increased in alcohol-treated Neuro2a cells owing to the impaired-spindle orientation. Meanwhile, the expression of Centrosome protein-J (CPAP) which plays an important role in spindle orientation was reduced in Neuro2a cells. The overexpression of GFP-CPAP in Neuro2a cells rescued the disorder of spindle orientation and the asymmetric cell division induced by alcohol. Taken together, the results demonstrate that alcohol exposure diminished the pool of proliferative Neuro2a cells through disordering the spindle orientation and promoting the asymmetric division. And these abnormal orientation and division were due to the reduced CPAP protein level.

Keywords: Alcohol; Asymmetric cell division; CPAP; Microcephaly; Spindle orientation.

MeSH terms

  • Animals
  • Asymmetric Cell Division / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Ethanol / toxicity*
  • Gene Expression Regulation / drug effects*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / antagonists & inhibitors*
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / drug effects
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Spindle Apparatus / drug effects*
  • Spindle Apparatus / metabolism

Substances

  • CENPJ protein, human
  • Cenpj protein, mouse
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Ethanol