β‐Amyloid peptide induces formation of actin stress fibers through p38 mitogen‐activated protein kinase

Abstract

Based on the critical role of actin in the maintenance of synaptic function, we examined whether expression of familial b-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-1 induced formation of actin stress fibers in SN1 cells, a septal neuronal cell line. Treatment with b-amyloid (Ab) peptide also caused formation of actin stress fibers in SN1 cells and primary cultured hippocampal neurons. Treatment with a c-secretase inhibitor completely blocked formation of actin stress fibers, indicating that overproduction of Ab 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 Ab 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 Ab peptide, IAPP or mPS1. Moreover, treatment with a c-secretase inhibitor completely blocked activation of p38MAPK and MAP-KAPK-2. In summary, our data suggest that overproduction of Ab peptide induces formation of actin stress fibers through activation of the p38MAPK signaling pathway in septal neuronal cells. Keywords: actin stress fibers, Alzheimer's disease, b-amyloid precursor protein, presenilin-1, p38 mitogen-activated protein kinase, mitogen-associated protein kinase-associated protein kinase.

Activation of p38 Has Opposing Effects on the Proliferation and Migration of Endothelial Cells

“…Several studies, as well as studies in our laboratory, have shown that inhibiting p38 can inhibit stress fiber formation in adherent cells and lead to decreases in cell permeability in some cell systems (57)(58)(59)(60). However, our data also indicate that no stress fiber formation accompanies the increase in lamellipodia formation observed in MEK6E-expressing cells replated onto gelatin.…”

γ-Secretase inhibitor DAPT sensitizes t-AUCB-induced apoptosis of human glioblastoma cells in vitro via blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway

“…Our results from the Western blot analysis showed that DAPT can block the t-AUCB-induced activation of the p38 MAPK/MAPKAPK2/ Hsp27 pathway, thus indicating that DAPT is a potential agent that can inhibit the t-AUCB-induced activation of Hsp27 and increase t-AUCB-induced apoptosis in glioblastoma cells. Although a study researching the formation of actin stress fibers [24] reported that a peptide, GSI (Z-Leu-Lyu-Nle-CHO), can completely block the activation of the p38 MAPK/MAP-KAPK2/Hsp27 pathway, almost no previous studies report that GSIs can be used to overcome chemoresistance in tumors by blocking the activation of the p38 MAPK/MAPKAPK2/ Hsp27 pathway. In the present study, we demonstrated that the GSI DAPT blocks the t-AUCB-induced activation of the p38 MAPK/MAPKAPK2/Hsp27 pathway in human GBM cells.…”

Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

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