title: Glutathione peroxidase-1 expression enhances recovery of human breast carcinoma cells from hyperoxic cell cycle arrest.
abstract: We previously reported that hyperoxia (95% O(2)) induces an S-phase cell cycle arrest in glutathione peroxidase-deficient human carcinoma cells T47D-H3 (Exp. Cell Res. 256:347-357; 2000). Here, we investigated whether increasing the peroxide scavenging capacity via glutathione peroxidase-1 (GPx1) expression can prevent cell cycle alterations induced by oxidative stress. We show that GPx1-proficient T47D-GPx-2 transfectant cells, in which GPx1 concentration is most elevated in mitochondria (Biochem. Biophys. Res. Commun. 272:416-422; 2000), are partially resistant to cell cycle inhibition induced by hyperoxia or menadione exposure. Transient cell growth resistance was observed at the level of cell cycle phase distribution, Cdk2 activity, and DNA synthesis after 40 h hyperoxia. This differential resistance was associated with an inhibition of ROS production and lipid peroxidation induced by hyperoxia. After 64 h hyperoxic exposure, cell growth was completely abolished in both cell lines, despite elevated glutathione levels. However, in contrast to the GPx1-deficient cells, T47D-GPx-2 cells showed an increased capacity to recover from a cell cycle arrest mediated by a 64 h hyperoxic stress. Differential recovery was also observed at the ultrastructural level between Gpx1-proficient and -deficient cells. These data indicate that GPx1 played an important role in the cell capacity to recover from hyperoxic insults. The limited protection conferred by GPx1 during hyperoxia suggests that the deleterious effects were partially mediated by peroxide-derived free radicals, but also involved the action of nonperoxide-derived reactive species.
authors.affiliation: Unit of Health, Laval University Medical Research Center, CHUL-CHUQ, Sainte-Foy, Québec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bilodeau
authors.forename: Alexandre
authors.initials: A
authors.lastname: Patenaude
authors.forename: Bruno
authors.initials: B
authors.lastname: Piedboeuf
authors.forename: Caroline
authors.initials: C
authors.lastname: Carrier
authors.forename: Peter
authors.initials: P
authors.lastname: Petrov
authors.forename: Robert
authors.initials: R
authors.lastname: Faure
authors.forename: Marc-Edouard
authors.initials: ME
authors.lastname: Mirault
mesh_terms: D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005609:Free Radicals; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human