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β‐Amyloid peptide induces formation of actin stress fibers through p38 mitogen‐activated protein kinase
Author(s) -
Song Cheng,
Perides George,
Wang Dechun,
Liu Ya Fang
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01182.x
Subject(s) - microbiology and biotechnology , protein kinase a , stress fiber , ask1 , actin , p38 mitogen activated protein kinases , amyloid precursor protein , kinase , chemistry , mitogen activated protein kinase kinase , biology , signal transduction , focal adhesion , medicine , alzheimer's disease , disease
Based on the critical role of actin in the maintenance of synaptic function, we examined whether expression of familial β‐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 β‐amyloid (Aβ) peptide also caused formation of actin stress fibers in SN1 cells and primary cultured hippocampal neurons. Treatment with a γ‐secretase inhibitor completely blocked formation of actin stress fibers, indicating that overproduction of Aβ 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 Aβ 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 Aβ peptide, IAPP or mPS1. Moreover, treatment with a γ‐secretase inhibitor completely blocked activation of p38MAPK and MAPKAPK‐2. In summary, our data suggest that overproduction of Aβ peptide induces formation of actin stress fibers through activation of the p38MAPK signaling pathway in septal neuronal cells.