Ah receptor involvement in mediation of pyruvate carboxylase levels and activity in mice given 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The arylhydrocarbon receptor (AhR) plays a central role in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in animals. The investigations described here provide evidence that support a role for the AhR in TCDD-mediated pyruvate carboxylase (PC) level/activity reductions in mice. Pyruvate carboxylase plays a pivotal role in gluconeogenesis and in supplying carbon units for the citric acid cycle. Delivered ip in a corn oil carrier, TCDD suppresses PC activity/amount at doses as low as 1 microgram/kg in responsive C57BL/6J(Ahb/b) mice. Corn oil alone injected ip into mice at 4 mL/kg appears to be an inducer that increases the amount and activity of PC. However, TCDD suppresses this induction. In the Ahb/b mouse, PC levels and activity are reduced to 10% of control values at a dose of 75 micrograms/kg. A time-course experiment shows that the PC reductions are apparent within 16 hours post-TCDD exposure. Here we report investigations on the PC/TCDD response using a congenic C57BL/6J(Ahd/d) mouse strain having an AhR with a low affinity for TCDD. If the PC/TCDD response is AhR mediated, the congenic mouse strain (Ahd/d) would require much higher doses of TCDD to suppress PC. In the Ahd/d mice, we observe that an approximately 60-fold increase in TCDD dose is necessary to produce a PC/TCDD effect. We also find that in Ahd/d mice, corn oil does not induce an increase in PC activity/amounts, as reported for Ahb/b mice.
Ryu
B W
BW
Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA.
Roy
S
S
Sparrow
B R
BR
Selivonchick
D P
DP
Schaup
H W
HW
D000818:Animals; D015153:Blotting, Western; D003314:Corn Oil / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011766:Pyruvate Carboxylase / Q000096:biosynthesis / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors
D007773:Lactates; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D003314:Corn Oil; D011766:Pyruvate Carboxylase