Title: Ah receptor involvement in mediation of pyruvate carboxylase levels and activity in mice given 2,3,7,8‐tetrachlorodibenzo‐<i>p</i>‐dioxin
Abstract: Abstract 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 μg/kg in responsive C57BL/6J(Ah b/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 Ah b/b mouse, PC levels and activity are reduced to 10% of control values at a dose of 75 μg/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(Ah d/d ) mouse strain having an AhR with a low affinity for TCDD. If the PC/TCDD response is AhR mediated, the congenic mouse strain (Ah d/d ) would require much higher doses of TCDD to suppress PC. In the Ah d/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 Ah d/d mice, corn oil does not induce an increase in PC activity/amounts, as reported for Ah b/b mice.
Publication Year: 1995
Publication Date: 1995-04-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 5
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