Gender divergent expression of Nqo1 in Sprague Dawley and August Copenhagen x Irish rats.
In the mammalian liver, there is an abundance of enzymes that function to enable the safe and efficient elimination of potentially harmful xenobiotics that are encountered through environmental exposure. A variety of factors, including gender and genetic polymorphisms, contribute to the variation between an individual system's detoxification capacity and thus its ability to protect itself against oxidative stress, cellular damage, cell death, etc. NAD(P)H:quinone oxidoreducatase 1 (Nqo1) is an antioxidant enzyme that plays a major role in reducing reactive electrophiles, thereby protecting cells from free-radical damage and oxidative stress. The goal of this study was to determine the gender-specific expression and inducibility of Nqo1 in the Sprague Dawley (SD) and August Copenhagen x Irish (ACI) rat strains, two strains that are commonly used in drug metabolism and drug-induced enzyme induction, toxicity, and carcinogenesis studies. Nqo1 mRNA, protein, and activity levels were determined through 96 h in SD and ACI males and females following treatment with known Nqo1 inducers oltipraz and butylated hydroxyanisole. In the SD strain, gender dimorphic expression of Nqo1 was observed with female mRNA, protein, and activity levels being significantly higher than in males. In contrast, there were minimal differences in Nqo1 mRNA, protein, and activity levels between ACI males and females. The gender dimorphic expression of Nqo1 in the SD rats was maintained through the course of induction, with female-induced levels greater than male-induced levels indicating that SD females may have a greater capacity to protect against oxidative stress and thus a decreased susceptibility to carcinogens.
Augustine
Lisa M
LM
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Fisher
Craig D
CD
Lickteig
Andrew J
AJ
Aleksunes
Lauren M
LM
Slitt
Angela L
AL
Cherrington
Nathan J
NJ
D000818:Animals; D015153:Blotting, Western; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006824:Hybridization, Genetic; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013871:Thiones; D013876:Thiophenes
D011719:Pyrazines; D012333:RNA, Messenger; D013871:Thiones; D013876:Thiophenes; D002083:Butylated Hydroxyanisole; C026209:oltipraz; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat