Jin Jin1, Lauren Richardson2, Samantha Sheller-Miller3, Nanbert Zhong4, Ramkumar Menon5. 1. Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No.1838, North Guangzhou Avenue, Guangzhou, 510515, China; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA. 2. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA; Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch at Galveston, Galveston, TX, USA. 3. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA. 4. New York State Institute for Basic Research in Development Disabilities, New York, NY, 10314, USA. 5. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA. Electronic address: ram.menon@utmb.edu.
Abstract
OBJECTIVE: This study tested the mechanism of the oxidative stress (OS)-induced senescence pathway at the feto-maternal interface cells. METHODS: 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. RESULTS: 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. CONCLUSION: OS induced p38MAPK activation and inflammation in all cell types that was associated with senescence in fetal cells but not in maternal cells.
OBJECTIVE: This study tested the mechanism of the oxidative stress (OS)-induced senescence pathway at the feto-maternal interface cells. METHODS: 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. RESULTS: 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. CONCLUSION: OS induced p38MAPK activation and inflammation in all cell types that was associated with senescence in fetal cells but not in maternal cells.
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