Prolonged hypoxia during cell development protects mature manganese superoxide dismutase-deficient astrocytes from damage by oxidative stress

Citation
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
Citations number
53
Categorie Soggetti
Experimental Biology
Journal title
FASEB JOURNAL
ISSN journal
08926638 → ACNP
Volume
15
Issue
2
Year of publication
2001
Pages
525 - 534
Database
ISI
SICI code
0892-6638(200102)15:2<525:PHDCDP>2.0.ZU;2-V
Abstract
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.