Direct contribution of inducible nitric oxide synthase expression to apoptosis induction in primary smooth chorion trophoblast cells of human fetal membrane tissues.
We have previously demonstrated that apoptosis induction is observed only in smooth chorion laeve trophoblast cells, and not in amnion epithelial cells of human fetal membrane tissues prepared at the term. Apoptosis induction was suppressed by the presence of an inhibitor specific for inducible nitric oxide synthase (iNOS), suggesting that intracellular oxidative stress plays a critical role in this process. In this study, we transfected the iNOS gene into primary cultured chorion and amnion cells to examine the direct contribution of iNOS gene expression to the apoptosis induction in these cells. We identified a significant increase in the levels of iNOS protein expression and nitrite accumulation in both chorion and amnion cells after the iNOS gene transfection. However, the induction of apoptosis was observed in an approximately 70% of chorion cells transfected with iNOS gene. Transfection of the iNOS gene into chorion cells resulted in the activation of p38 mitogen-activated protein kinase (MAPK) and downregulation of hemeoxygenase-1 protein expression, whereas no such events were observed in the transfected amnion cells. These results suggest that apoptosis induced in the chorion trophoblast cells by the iNOS gene expression is closely linked to a physiological consequence, such as the rupture of fetal membranes.
Yuan
Bo
B
Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan. yuanbo@ps.toyaku.ac.jp
Ohyama
Kunio
K
Takeichi
Makoto
M
Toyoda
Hiroo
H
D000650:Amnion / Q000166:cytology / Q000201:enzymology; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002823:Chorion / Q000166:cytology* / Q000201:enzymology*; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology* / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases