Induction of Xanthine Oxidase by TCDD.
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Accession number;00A0997666
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| Title;Induction of Xanthine Oxidase by TCDD. |
| Author;
SUGIHARA KAZUMI
(Hiroshima Univ., Sch. of Med.)
YAMADA TSUYOSHI
(Hiroshima Univ., Sch. of Med.)
KITAMURA SHIGEYUKI
(Hiroshima Univ., Sch. of Med.)
OTA SHIGERU
(Hiroshima Univ., Sch. of Med.)
KANO YUKARI
(Hiroshima Univ., Sch. of Med.)
OKAMURA SAORI
(Hiroshima Univ., Sch. of Med.)
YAMASHITA KEISUKE
(Hiroshima Univ., Sch. of Med.)
YASUDA MINEO
(Hiroshima Univ., Sch. of Med.)
FUJII YOSHIAKI
(Tohoku Univ., Grad. Sch.)
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Journal Title;Xenobiotic Metabolism and Disposition
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Journal Code:X0758A
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ISSN:0916-1139
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VOL.15;NO.Supplement;PAGE.S80-S81(2000)
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| Figure&Table&Reference;FIG.1, REF.2 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) is one of the most toxic polychlorinated organic pollutants that have been studied. Most of the effects of TCDD are mediated by a cytosolic receptor known to as the aryl hydrocarbon receptor(AhR). Several xenobiotic-metabolizing enzymes, such as cytochrome P450 1A1(CYP1A1), 1A2(CYP1A2), UDP-glucuronosyltransferase, NAD(P)H-quinone oxidoreductase, and aldehyde dehydrogenase-3, have the XRE sequences, AhR-ARNT complex binding motif, in the 5'-upstream region of their genes and AhR-mediated induction of gene expression by TCDD is observed. The inductions of EROD and MROD activities by TCDD were proved to be mediated by AhR, since TCDD treatment of AhR-null(Ahr-/-) mice, which lack the AhR gene, produced no enhancement of EROD and MROD activities in liver microsomes. Xanthine dehydrogenase(XDH) and xanthine oxidase(XO) activities of Ahr+/+(C57BL/6J) mice were also increased by TCDD. However, no induction was observed in Ahr-/- mice. Thus, induction of XDH and XO activities was also mediated by AhR. XDH and XO catalyze oxidation of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of NAD+ or molecular oxygen. The reaction generates reactive oxygen species, and XO is involved in lipid peroxidation and reperfusion injury. Reactive oxygen species are generated as by-products of the action of XO/XDH. Therefore, the induction of these enzymes by TCDD may contribute significantly to the various toxicities of TCDD. In this study, we showed that XDH/XO activities are induced by TCDD and the inductions are mediated by AhR. (author abst.) |
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