RRC ID 32239
Author Cinq-Frais C, Coatrieux C, Savary A, D'Angelo R, Bernis C, Salvayre R, Nègre-Salvayre A, Augé N.
Title Annexin II-dependent actin remodelling evoked by hydrogen peroxide requires the metalloproteinase/sphingolipid pathway.
Journal Redox Biol
Abstract Actin remodeling is a dynamic process associated with cell shape modification occurring during cell cycle and proliferation. Oxidative stress plays a role in actin reorganization via various systems including p38MAPK. Beside, the mitogenic response evoked by hydrogen peroxide (H2O2) in fibroblasts and smooth muscle cells (SMC) involves the metalloproteinase (MMPs)/sphingomyelinase 2 (nSMase2) signaling pathway. The aim of this work was to investigate whether this system plays a role in actin remodeling induced by H2O2. Low H2O2 dose (5µM) rapidly triggered a signaling cascade leading to nSMase2 activation, src and annexin 2 (AnxA2) phosphorylation, and actin remodeling, in fibroblasts and SMC. These events were blocked by pharmacological inhibitors of MMPs (Ro28-2653) and p38MAPK (SB203580), and were lacking in MMP2(-/-) and in nSMase2-mutant (fro) fibroblasts. Likewise, H2O2 was unable to induce actin remodeling in fro and MMP2(-/-) fibroblasts or in cells pretreated with p38MAPK, or MMP inhibitors. Finally we show that nSMase2 activation by H2O2, depends on MMP2 and p38MAPK, and is required for the src-dependent phosphorylation of AnxA2, and actin remodeling. Taken together, these findings indicate for the first time that AnxA2 phosphorylation and actin remodeling evoked by oxidative stress depend on the sphingolipid pathway, via MMP2 and p38MAPK.
Volume 4
Pages 169-79
Published 2015
DOI 10.1016/j.redox.2014.12.005
PII S2213-2317(14)00129-3
PMID 25574848
PMC PMC4309845
MeSH Actins / metabolism* Animals Annexin A2 / biosynthesis Annexin A2 / metabolism* Cell Proliferation / drug effects Fibroblasts / metabolism Humans Hydrogen Peroxide / pharmacology Matrix Metalloproteinase 2 / biosynthesis Matrix Metalloproteinase 2 / metabolism* Mice Myocytes, Smooth Muscle / metabolism Myocytes, Smooth Muscle / pathology Oxidative Stress / drug effects Phosphorylation Signal Transduction / drug effects Sphingolipids / metabolism p38 Mitogen-Activated Protein Kinases / biosynthesis p38 Mitogen-Activated Protein Kinases / metabolism*
IF 7.126
Resource
Mice B6.129P2-Mmp2<tm1Ito>/ItoRbrc(RBRC00398)