title: Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges.
abstract: Oxidative stress results from the imbalance between reactive oxygen species (ROS) and ROS-scavenging molecules. Among them, cytosolic glutathione peroxidase (GPX1) plays a major role as it reduces a large part of intracellular ROS. Endothelial cells are a barrier for potentially aggressive molecules circulating in the blood stream and, therefore, are often under great oxidative stress. Thus, we investigated the potentially protective effects of GPX1 overexpression in the endothelial cell line, ECV304. We found that chronic GPX1 overexpression delays cell growth without affecting viability or decreasing resistance to hydrogen peroxide-induced oxidative stress. As GPX1 overexpression could drain the cellular reduced glutathione (GSH) pool, we also tested the effects of extracellular GSH supplementation on cell growth. Despite its largely referenced beneficial effects for cells, GSH was toxic for ECV304 cells in a dose-dependent manner but GSH-induced toxicity was reduced in selenium supplemented cultures and completely abolished in ECV304 overexpressing GPX1, compared to control. In summary, GPX1 overexpression delays cell growth and protects them from GSH and H(2)O(2) toxicity.
authors.affiliation: Laboratory of Medicinal Biochemistry, Faculty of Medicine, University of Limoges, 2 rue du Dr. Raymond-Marcland, 87025 Limoges, France. karine.faucher@unilim.fr
authors.forename: K
authors.initials: K
authors.lastname: Faucher
authors.forename: H
authors.initials: H
authors.lastname: Rabinovitch-Chable
authors.forename: G
authors.initials: G
authors.lastname: Barrière
authors.forename: J
authors.initials: J
authors.lastname: Cook-Moreau
authors.forename: M
authors.initials: M
authors.lastname: Rigaud
mesh_terms: D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*
chemical_list: D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione