Expression of hepatic pyruvate carboxylase mRNA in C57BL/6J Ah(b/b) and congenic Ah((d/d)) mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The activity and level of hepatic pyruvate carboxylase (PC) has been reported to be altered by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in mice. If alteration in PC level/activity by TCDD influences TCDD toxicity, one would expect to observe an early post-exposure reduction in PC mRNA. To examine the molecular events responsible for the alteration of PC activity in livers of TCDD-treated mice, we designed a synthetic DNA oligonucleotide probe specific for PC mRNA. Northern blot analysis on RNA extracts from hepatic tissue at various times and doses post-TCDD exposure were done. Furthermore, to elucidate the role of the dioxin Ah locus on alterations of PC activity by TCDD, we utilized C57BL/6J (Ahb/b, Ah high TCDD affinity) mice and a congenic (Ahd/d, AH low TCDD affinity) mouse strain. At 8 days post TCDD treatment, a dose-dependent reduction of hepatic PC mRNA levels was observed in Ahb/b mice. The response, reduction in PC mRNA levels, in the Ahb/b strain was about 10-fold greater than that of comparably exposed congenic Ahd/d mice. These results indicate that previously reported reductions in PC activity/level by TCDD treatment of mice is a consequence of a reduction in PC mRNA levels and that the effect requires a competent Ah receptor.
Ilian
M A
MA
Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA.
Sparrow
B R
BR
Ryu
B W
BW
Selivonchick
D P
DP
Schaup
H W
HW
D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D015345:Oligonucleotide Probes; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011766:Pyruvate Carboxylase / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity
D015345:Oligonucleotide Probes; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011766:Pyruvate Carboxylase