Am. J. Respir. Cell Mol. Biol., Volume 24, Number 4, April, 2001 436-441

Overexpression of Manganese Superoxide Dismutase Protects Lung Epithelial Cells against Oxidant Injury

Anatoliy M. Ilizarov, Hshi-Chi Koo, Jeffrey A. Kazzaz, Lin L. Mantell, Yuchi Li, Ritu Bhapat, Simcha Pollack, Stuart Horowitz, and Jonathan M. Davis

CardioPulmonary Research Institute and Departments of Pediatrics, Medicine (Pulmonary and Critical Care Medicine), Thoracic-Cardiovascular Surgery, and Biostatistics, Winthrop University Hospital, State University of New York Stony Brook School of Medicine, Mineola, New York; Department of Computer Information Systems and Decision Sciences, St. John's University, Jamaica, New York; and Heart and Lung Institute, Jewish Hospital, Lexington, Kentucky

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% O₂ 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.

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