Akt up- and down-regulation in response to endoplasmic reticulum stress

Brain Res. 2007 Jun 4;1152:27-31. doi: 10.1016/j.brainres.2007.03.052. Epub 2007 Mar 24.

Abstract

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of CNS diseases such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia. In the present study, we found that Akt activation is regulated dually by ER stress in primary cultured glial cells. We observed that Akt activation was increased by short-term exposure to ER stress but was down-regulated by long-term exposure to ER stress. ER stress-induced Akt activation was mediated through phosphatidylinositol 3-kinase (PI3K) because the PI3K inhibitors, LY294002 and wortmannin, inhibited Akt activation. Moreover, Akt was localized in the ER, as assessed by immunohistochemistry, and ER stress increased microsomally localized Akt activation. These results suggest that Akt plays an important role in stress conditions, which impair ER function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / cytology
  • Cells, Cultured
  • Down-Regulation
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / enzymology*
  • Enzyme Activation
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Neuroglia / drug effects
  • Neuroglia / enzymology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / biosynthesis*
  • Proto-Oncogene Proteins c-akt / genetics
  • Subcellular Fractions / enzymology
  • Thapsigargin / pharmacology
  • Tunicamycin / pharmacology
  • Up-Regulation

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Tunicamycin
  • Thapsigargin
  • Proto-Oncogene Proteins c-akt