Developmental changes in murine brain antioxidant enzymes.
Reactive oxygen species produced in cells during normal aerobic metabolism have the ability to induce lipid peroxidation and protein oxidation; therefore, their detoxification and elimination are necessary for physiologic cellular activity and survival. The changes in neuronal antioxidant enzymes from fetal life to adulthood have not been fully described. We investigated protein expression, using Western blot analysis, and enzymatic activity of the antioxidant system-copper-zinc superoxide dismutase (SOD), manganese SOD, catalase, and glutathione peroxidase, as well as reduced glutathione level as an indicator of the nonenzymatic system-in CD1 murine brain at embryonic d 18 (E18), and postnatal d 1 (P1), d 4, d 7, d 14, and d 21. Copper-zinc SOD and glutathione peroxidase protein levels were low, whereas manganese SOD and catalase protein levels were high at E18 and P1. Total SOD activity was high at E18 and P1 and paralleled elevated manganese SOD activity; however, copper-zinc SOD activity was relatively unchanged throughout development. Catalase activity doubled and glutathione peroxidase activity tripled between E18 and P1. Reduced glutathione increased between E18 and P1. Except for catalase and manganese SOD, peak protein levels do not occur until later developmental ages. We suggest that as the fetus moves from an in utero hypoxic to a relatively hyperoxic environment with an approximate 4-fold elevation in oxygen concentration, these developmental changes in antioxidant enzymes are compensatory mechanisms aimed at protecting the newborn from oxidative stress. These data will be important in our future understanding of the mechanisms by which hypoxia mediates injury in the immature and the mature brain.
Khan
Janine Y
JY
Department of Pediatrics and Molecular Pharmacology, Northwestern University, Chicago, IL 60611, USA.
Black
Stephen M
SM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen