Jc. Copin et al., Prolonged hypoxia during cell development protects mature manganese superoxide dismutase-deficient astrocytes from damage by oxidative stress, FASEB J, 15(2), 2001, pp. 525-534
Mouse astrocytes deficient in the mitochondrial form of superoxide dismutas
e do not grow in culture under 20% atmospheric O-2 levels, By flaw cytometr
y, immunocytochemistry, and enzymatic analysis we have shown that the oxyge
n block of cell division is due to a decrease in the number of cells enteri
ng the S phase of the cell cycle and is concomitant with higher DNA oxidati
on and impairment of mitochondrial functions. Seeding the cells under 5% O-
2 until the cultures become confluent can circumvent this problem. An initi
al hypoxic environment increases the resistance of manganese superoxide dis
mutase-deficient astrocytes to superoxide radicals artificially produced by
paraquat treatment, preserves respiratory activity, and allows normoxic di
vision during a subsequent passage. DNA oxidation is then not higher than i
ll 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, Alteratio
n of the phenotype by prior hypoxia exposure in the SOD2-deficient mutant p
rovide a unique model to study adaptative mechanisms of cellular resistance
to oxygen toxicity.