Upregulated Expression of Karyopherin α2 is Involved in Neuronal Apoptosis Following Intracerebral Hemorrhage in Adult Rats

Cell Mol Neurobiol. 2016 Jul;36(5):755-65. doi: 10.1007/s10571-015-0258-7. Epub 2015 Sep 4.

Abstract

Karyopherin α2 (KPNA2) plays a central role in nucleocytoplasmic transport. It is involved in controlling the flow of genetic information and the modulation of diverse cellular activities. Here we explored the KPNA2's roles during the pathophysiological processes of intracerebral hemorrhage (ICH). An ICH rat model was built and evaluated according to behavioral testing. Using Western blot, immunohistochemistry, and immunofluorescence, significant upregulation of KPNA2 was found in neurons in brain areas surrounding the hematoma following ICH. Increasing KPNA2 level was found to be accompanied by the upregulation of active caspase-3, Bax, and decreased expression of Bcl-2. Besides, KPNA2 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. What's more, knocking down KPNA2 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, KPNA2 may play a role in promoting the brain secondary damage following ICH.

Keywords: Intracerebral hemorrhage; KPNA2; Neuronal apoptosis; Rat.

MeSH terms

  • Aging
  • Animals
  • Apoptosis / physiology*
  • Caspase 3 / metabolism
  • Cerebral Hemorrhage / metabolism*
  • Hematoma / metabolism
  • Male
  • Neurons / cytology
  • Neurons / metabolism*
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Transcriptional Activation / physiology
  • Up-Regulation
  • alpha Karyopherins / metabolism*

Substances

  • alpha Karyopherins
  • karyopherin alpha 2
  • Casp3 protein, rat
  • Caspase 3