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Relationship of resistance to oxygen free radicals to CuZn‐superoxide dismutase activity in transgenic, transfected, and trisomic cells
Author(s) -
Huang TingTing,
Carlson Elaine J.,
Leadon Steven A.,
Epstein Charles J.
Publication year - 1992
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.6.3.1740238
Subject(s) - superoxide dismutase , paraquat , microbiology and biotechnology , chemistry , glutathione peroxidase , catalase , toxicity , transgene , biology , oxidative stress , biochemistry , organic chemistry , gene
Although CuZn‐superoxide dismutase (CuZnSOD) has been shown to reduce oxidative damage in several systems, the quantitative relationship between the degree of protection and CuZnSOD activity has not been well investigated. Therefore, the ability of cells to tolerate superoxide toxicity was assessed as a function of endogenous CuZnSOD activity in several mouse and human cell lines with progressively higher levels of CuZnSOD activity. In five lines of fetal fibroblasts derived from SOD1 ‐transgenic mice, with CuZnSOD activities of 1.7‐ to 7.1‐fold the nontransgenic level and no changes in the cellular glutathione peroxidase (GSHPx) activity, a direct relationship ( r = 0.97) between the LD 50 to paraquat and enzyme activity was observed, suggesting that CuZnSOD activity is the single most important factor in determining the paraquat LD 50 . Mouse trisomy 16 fetal fibroblasts and human trisomy 21 lung fibroblasts, both expressing a 1.5‐fold increase in CuZnSOD activity, were 1.5‐fold more tolerant to paraquat than were their diploid counterparts. Furthermore, the protective effect of CuZnSOD at the DNA level, as shown by reduced thymine glycol generation, was demonstrated in paraquat‐treated transgenic fibroblasts. A direct relationship ( r = 0.78) of paraquat LD 50 and CuZnSOD activity was also observed with a panel of six lines of SOD1 ‐ transfected HeLa cells with 1.6‐ to 7.3‐fold the basal CuZnSOD activity. Moreover, there was no correlation between resistance to paraquat toxicity and the cellular GSHPx and/or catalase activity. Taken together, these results demonstrate a consistently protective effect of endogenous CuZnSOD against superoxide toxicity in both primary and transformed cell lines.—Huang, T.‐ T.; Carlson, E. J.; Leadon, S. A.; Epstein, C. J. Relationship of resistance to oxygen free radicals to CuZn‐superoxide dismutase activity in transgenic, transfected, and trisomie cells. FASEB J. 6: 903‐910; 1992.