PC12 cells transfected with a C-terminal fragment of the amyloid precursor protein (APP C-100), exhibit enhanced sensitivity to the calcium ionophore A23187, and diminished sensitivity to hydrogen peroxide

Brain Res Mol Brain Res. 1999 Sep 8;72(1):103-7. doi: 10.1016/s0169-328x(99)00228-4.

Abstract

Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is Abeta, a 39-43 amino acid peptide derived from the amyloid precursor protein (APP). APP C-100 is a C-terminal fragment of APP, 100 amino acids long, whose sequence includes Abeta. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H(2)O(2), rat PC12 cells were modified to overexpress APP C-100. Cellular survival (as measured in the MTT assay) was determined as a function of concentration for the calcium ionophore, A23187, and for H(2)O(2) in APP C-100 transfectants and vector-transfected controls. APP C-100 expression significantly increased cellular vulnerability to A23187, and decreased vulnerability to H(2)O(2).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / physiology*
  • Animals
  • Calcimycin / pharmacology*
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Drug Resistance
  • Hydrogen Peroxide / pharmacology*
  • Ion Transport / drug effects
  • Ionophores / pharmacology*
  • Neurons / drug effects*
  • PC12 Cells
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology*
  • Rats
  • Recombinant Fusion Proteins / physiology
  • Transfection

Substances

  • Amyloid beta-Protein Precursor
  • Ionophores
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • amyloid precursor protein, carboxy-terminal 100 residues
  • Calcimycin
  • Hydrogen Peroxide
  • Calcium