title: Overexpression of manganese superoxide dismutase protects lung epithelial cells against oxidant injury.
abstract: To determine whether overexpression of antioxidant enzymes in lung epithelial cells prevents damage from oxidant injury, stable cell lines were generated with complementary DNAs encoding manganese superoxide dismutase (MnSOD) and/or catalase (CAT). Cell lines overexpressing MnSOD, CAT, or MnSOD + CAT were assessed for tolerance to hyperoxia or paraquat. After exposure to 95% O(2) for 10 d, 44 to 57% of cells overexpressing both MnSOD and CAT and 37 to 47% of cells overexpressing MnSOD alone were viable compared with 7 to 12% of empty vector or parental cells (P < 0.05). To assess if viable cells were capable of cell division after hyperoxic exposures (up to 5 d), a clonogenicity assay was performed. The clonogenic potential of cells overexpressing MnSOD + CAT and MnSOD alone were significantly better than those expressing CAT alone or empty vector controls. In addition, 54 to 72% of cells overexpressing both MnSOD and CAT survived in 1 mM paraquat compared with 58 to 73% with MnSOD alone and 27% with control cells. Overexpression of CAT alone did not improve survival in hyperoxia or paraquat. The combination of MnSOD + CAT did not provide additional protection from paraquat. Data demonstrate that overexpression of MnSOD protects cells from oxidant injury and CAT offers additional protection from hyperoxic injury when co-expressed with MnSOD.
authors: CardioPulmonary Research Institute, Winthrop University Hospital, State University of New York Stony Brook School of Medicine, Mineola, New York 11501, USA.
authors: A M
authors: AM
authors: Ilizarov
authors: H C
authors: HC
authors: Koo
authors: J A
authors: JA
authors: Kazzaz
authors: L L
authors: LL
authors: Mantell
authors: Y
authors: Y
authors: Li
authors: R
authors: R
authors: Bhapat
authors: S
authors: S
authors: Pollack
authors: S
authors: S
authors: Horowitz
authors: J M
authors: JM
authors: Davis
mesh_terms: D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006367:HeLa Cells; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D010269:Paraquat / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
chemical_list: D006540:Herbicides; D016877:Oxidants; D012333:RNA, Messenger; D002374:Catalase; D013482:Superoxide Dismutase; D010269:Paraquat