Prolonged hypoxia during cell development protects mature manganese superoxide dismutase-deficient astrocytes from damage by oxidative stress.
Mouse astrocytes deficient in the mitochondrial form of superoxide dismutase do not grow in culture under 20% atmospheric O2 levels. By flow cytometry, immunocytochemistry, and enzymatic analysis we have shown that the oxygen block of cell division is due to a decrease in the number of cells entering the S phase of the cell cycle and is concomitant with higher DNA oxidation and impairment of mitochondrial functions. Seeding the cells under 5% O2 until the cultures become confluent can circumvent this problem. An initial hypoxic environment increases the resistance of manganese superoxide dismutase-deficient astrocytes to superoxide radicals artificially produced by paraquat treatment, preserves respiratory activity, and allows normoxic division during a subsequent passage. DNA oxidation is then not higher than in wild-type control cells. However, the adaptation of the cells is not due to compensation by other enzymes of the antioxidant defense system and is specific to cells totally lacking manganese superoxide dismutase. Alteration of the phenotype by prior hypoxia exposure in the SOD2-deficient mutant provide a unique model to study adaptative mechanisms of cellular resistance to oxygen toxicity.
Copin
J C
JC
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305-5487 USA.
Gasche
Y
Y
Li
Y
Y
Chan
P H
PH
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004247:DNA / Q000096:biosynthesis; D005979:Glutathione Peroxidase / Q000378:metabolism; D006720:Homozygote; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D004247:DNA; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase