beta-Amyloid peptide induces formation of actin stress fibers through p38 mitogen-activated protein kinase

J Neurochem. 2002 Nov;83(4):828-36. doi: 10.1046/j.1471-4159.2002.01182.x.

Abstract

Based on the critical role of actin in the maintenance of synaptic function, we examined whether expression of familial beta-amyloid precursor protein APP-V642I (IAPP) or mutant presenilin-1 L286V (mPS1) affects actin polymerization in rat septal neuronal cells. Expression of either IAPP or mPS1 but not wild-type amyloid precursor protein or presenilin-1induced formation of actin stress fibers in SN1 cells, a septal neuronal cell line. Treatment with beta-amyloid (Abeta) peptide also caused formation of actin stress fibers in SN1 cells and primary cultured hippocampal neurons. Treatment with a gamma-secretase inhibitor completely blocked formation of actin stress fibers, indicating that overproduction of Abeta peptide induces actin stress fibers. Because activation of the p38 mitogen-activated protein kinase (p38MAPK)-mitogen-associated protein kinase-associated protein kinase (MAPKAPK)-2-heat-shock protein 27 signaling pathway mediates actin polymerization, we explored whether Abeta peptide activates p38MAPK and MAPKAPK-2. Expression of IAPP or mPS1 induced activation of p38MAPK and MAPKAPK-2. Treatment with a p38MAPK inhibitor completely inhibited formation of actin stress fibers mediated by Abeta peptide, IAPP or mPS1. Moreover, treatment with a gamma-secretase inhibitor completely blocked activation of p38MAPK and MAPKAPK-2. In summary, our data suggest that overproduction of Abeta peptide induces formation of actin stress fibers through activation of the p38MAPK signaling pathway in septal neuronal cells.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Alzheimer Disease / genetics
  • Amino Acid Substitution
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / pharmacology*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / pharmacology
  • Animals
  • Aspartic Acid Endopeptidases
  • Cell Line
  • Cells, Cultured
  • Endopeptidases / drug effects
  • Enzyme Inhibitors / pharmacology
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins*
  • Hippocampus / cytology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Chaperones
  • Mutation
  • Neoplasm Proteins / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Presenilin-1
  • Protein-Serine-Threonine Kinases / metabolism
  • Rats
  • Signal Transduction / physiology
  • Stress Fibers / metabolism*
  • Transfection
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Actins
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Enzyme Inhibitors
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Hsbp1 protein, mouse
  • Hspb1 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • Neoplasm Proteins
  • Presenilin-1
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse