Inhibition of cell growth and sensitization to oxidative damage by overexpression of manganese superoxide dismutase in rat glioma cells.
The effects of overexpression of human manganese superoxide dismutase (MnSOD) on cell proliferation and response to oxidative stress in rat glioma cells were studied. MnSOD-overexpressing cells had a 2- to 14-fold increase in MnSOD activity, but did not have consistent changes in the activities of CuZnSOD, catalase, or glutathione peroxidase. Cells with more than a 5-fold increase in MnSOD activity became more sensitive to radiation, 1,3-bis(2-chloroethyl)-1-nitrosourea, and buthionine sulfoximine and had a lower growth rate than parental and vector control cells. The sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea was partially reduced by pyruvate, a H2O2 scavenger. Our results suggest that overexpression of MnSOD can cause an imbalance of antioxidant enzymes, which we hypothesize results in an elevation of intracellular H2O2. Overexpression of MnSOD can either inhibit cell proliferation or increase cell death by oxidative agents, depending on the levels of peroxide-removing enzymes.
Zhong
W
W
Radiation Research Laboratory, University of Iowa, Iowa City 52242, USA.
Oberley
L W
LW
Oberley
T D
TD
Yan
T
T
Domann
F E
FE
St Clair
D K
DK
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D015870:Gene Expression; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress / Q000502:physiology*; D019289:Pyruvic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011836:Radiation Tolerance; D051381:Rats; D013482:Superoxide Dismutase / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019328:Buthionine Sulfoximine; D019289:Pyruvic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase; D002330:Carmustine