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Title: Oxidative stress induces p38MAPK-dependent senescence in the feto-maternal interface cells.

Authors: Jin, Jin; Richardson, Lauren; Sheller-Miller, Samantha; Zhong, Nanbert; Menon, Ramkumar

Published In Placenta, (2018 Jul)

Abstract: This study tested the mechanism of the oxidative stress (OS)-induced senescence pathway at the feto-maternal interface cells.Primary amnion mesenchymal cells (AMCs), chorion and decidual cells isolated from the placental membranes of women at normal term (not in labor) were exposed to OS-inducing cigarette smoke extract (CSE) for 48 h. Reactive oxygen species (ROS) was measured using 2'7'-dichlorodihydrofluorescein. Western blot analysis determined phosphorylated (P) p38MAPK and p53 expression. Senescence-associated β-Galactosidase (SA-β-Gal) and matrix metallopeptidase 9 (MMP9) histochemistry were used to measure senescence and inflammation respectively. Cotreatment of cells with the antioxidant, N-acetyl cysteine (NAC), or the p38MAPK inhibitor, SB203580 (SB), verified the activation specificity.CSE increased ROS production from AMCs, chorion cells, and decidual cells (P < 0.05) compared to controls. Western blot analysis determined that CSE induced p38MAPK activation (P < 0.05) and cotreatment with NAC inhibited ROS production and p38MAPK activation (P < 0.05) in all cell types. CSE did not increase p53 phosphorylation in any of the cells; however, AMCs showed constitutive P-p53 expression. CSE increased senescence in AMCs and chorion cells compared to controls (P = 0.01 and P = 0.003, respectively); however, senescence was not observed in decidual cells. Senescence was significantly reduced following cotreatment with SB and NAC (AMCs; P = 0.01 and chorion; P = 0.009). CSE increased MMP9 in all cells that was reduced by NAC.OS induced p38MAPK activation and inflammation in all cell types that was associated with senescence in fetal cells but not in maternal cells.

PubMed ID: 29941169 Exiting the NIEHS site

MeSH Terms: Amnion/cytology*; Amnion/metabolism; Cells, Cultured; Cellular Senescence*; Decidua/cytology*; Decidua/metabolism; Epithelial Cells/metabolism; Epithelial Cells/physiology*; Female; Humans; Maternal-Fetal Relations; Oxidative Stress/drug effects; Oxidative Stress/physiology*; Placenta/cytology*; Placenta/metabolism; Pregnancy; Reactive Oxygen Species/metabolism; Smoke/adverse effects; Stromal Cells/cytology; Stromal Cells/physiology; Tobacco; Up-Regulation; p38 Mitogen-Activated Protein Kinases/metabolism; p38 Mitogen-Activated Protein Kinases/physiology*

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