Estrogen Stimulates Release of Secreted Amyloid Precursor Protein From Primary Rat Cortical Neurons via Protein Kinase C Pathway

Acta Pharmacol Sin. 2005 Feb;26(2):171-6. doi: 10.1111/j.1745-7254.2005.00538.x.

Abstract

Aim: To investigate the mechanism of the action of estrogen, which stimulates the release of secreted amyloid precursor protein alpha (sAPP(alpha)) and decreases the generation of amyloid-beta protein (A(beta)), a dominant component in senile plaques in the brains of Alzheimer's disease patients.

Methods: Experiments were carried out in primary rat cortical neurons, and Western blot was used to detect sAPP(alpha) in a culture medium and the total amount of cellular amyloid precursor protein (APP) in neurons.

Results: 17beta-Estradiol (but not 17alpha-estradiol) and beta-estradiol 6-(O-carboxymethyl) oxime: BSA increased the secretion of sAPP(alpha) and this effect was blocked by protein kinase C (PKC) inhibitor calphostin C, but not by the classical estrogen receptor antagonist ICI 182,780. Meanwhile, 17beta-estradiol did not alter the synthesis of cellular APP.

Conclusion: The effect of 17beta-estradiol on sAPP(alpha) secretion is likely mediated through the membrane binding sites, and needs molecular configuration specificity of the ligand. Furthermore, the action of the PKC-dependent pathway might be involved in estrogen-induced sAPP(alpha) secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Female
  • Male
  • Naphthalenes / pharmacology
  • Neurons / metabolism
  • Peptide Fragments / metabolism*
  • Protein Kinase C / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Amyloid beta-Protein Precursor
  • Naphthalenes
  • Peptide Fragments
  • alpha-sAPP protein, human
  • Estradiol
  • Protein Kinase C
  • calphostin C