Abstract
The role of aromatic hydrocarbon receptor (AhR)-mediated signal transduction pathways was investigated in the regulation of ascorbate synthesis by using Ah-responsive and Ah-unresponsive mouse strains. In vivo 3-methylcholanthrene treatment increased hepatic and plasma ascorbate concentrations only in the Ah-responsive strain. The mRNA level of gulonolactone oxidase and the microsomal ascorbate production from p-nitrophenyl glucuronide, D-glucuronic acid or gulonolactone in the liver of Ah-responsive and Ah-unresponsive mice were compared. In Ah-responsive mice, these parameters were higher originally, and they further increased upon in vivo addition of 3-methylcholanthrene, while in Ah-unresponsive mice the treatment was not effective. These results suggest that the transcription of gulonolactone oxidase gene is regulated by an Ah receptor-dependent signal transduction pathway.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ascorbic Acid / blood
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Ascorbic Acid / metabolism
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Cytochrome P-450 CYP1A1 / biosynthesis
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Glucaric Acid / analogs & derivatives
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Glucuronates*
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Glucuronic Acid / metabolism
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Glucuronides / metabolism
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Glucuronosyltransferase / biosynthesis
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L-Gulonolactone Oxidase
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Male
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Methylcholanthrene / pharmacology
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Mice
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Mice, Inbred Strains
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Microsomes, Liver / metabolism
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RNA, Messenger / biosynthesis
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Receptors, Aryl Hydrocarbon / drug effects
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Receptors, Aryl Hydrocarbon / metabolism*
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Signal Transduction
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Sugar Alcohol Dehydrogenases / biosynthesis*
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Time Factors
Substances
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Glucuronates
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Glucuronides
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RNA, Messenger
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Receptors, Aryl Hydrocarbon
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4-nitrophenylglucuronide
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Methylcholanthrene
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saccharolactone
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Glucuronic Acid
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Sugar Alcohol Dehydrogenases
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L-Gulonolactone Oxidase
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Cytochrome P-450 CYP1A1
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UDP-glucuronosyltransferase, UGT1A6
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Glucuronosyltransferase
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Ascorbic Acid
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Glucaric Acid