"Oxidative stress" response in liver of an untreated newborn mouse having a 1.2-centimorgan deletion on chromosome 7.
The c14CoS/c14CoS mouse has a homozygous deletion of about 1.2 cM on chromosome 7 that includes the albino (c) locus. The untreated 14CoS/14CoS newborn has been reported to exhibit a marked transcriptional activation of the hepatic NAD(P)H:menadione oxidoreductase (Nmo-1; DT diaphorase; quinone reductase; azo dye reductase) gene, as well as elevated UDP glucuronosyl-transferase (UGT1*06) and glutathione transferase (GT1) activities, when compared with the cch/cch wild-type and the cch/c14CoS heterozygote. We show here that the newborn hepatic activities of seven enzymes that play a role in the oxidative stress response--NMO1, UGT1*06, GT1, copper-zinc superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase--are increased 1.5- to 25-fold in 14CoS/14CoS, as compared with ch/ch and ch/14CoS mice. The activities of four additional enzymes having no known association with the oxidative stress response--benzo[a]pyrene hydroxylase (CYP1A1, cytochrome P(1)450), acetanilide 4-hydroxylase (CYP1A2, cytochrome P(3)450), lactate dehydrogenase (LDH), and NADPH-cytochrome c reductase--are not significantly different among the three genotypes. These data suggest that there exists an "oxidative stress" response in the untreated 14CoS/14CoS newborn. We postulate that a chromosome 7 regulatory gene, which we have named Nmo-1n, might encode a trans-acting negative effector of the Nmo-1 gene, and genes corresponding to the other elevated enzymic activities described above. When both copies of Nmo-1n are deleted, as is the case in 14CoS/14CoS mice, a battery of genes involved in oxidative stress is released from negative control and becomes activated--despite the absence of any apparent oxidative insult by foreign chemicals.
Liang
H C
HC
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
Shertzer
H G
HG
Nebert
D W
DW
D000818:Animals; D000831:Animals, Newborn; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D011809:Quinones / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D011809:Quinones; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase