Tissue-specific expression of the mouse dioxin-inducible P(1)450 and P(3)450 genes: differential transcriptional activation and mRNA stability in liver and extrahepatic tissues.

Kimura, Shioko; Gonzalez, Frank J.; Nebert, Daniel W.

doi:10.1128/mcb.6.5.1471

Cited by 170 publications

(46 citation statements)

References 37 publications

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“…This would be especially true if CYP1A2 served as a watchdog of metabolic activities directly mediated by other substances, such as hormones and cytokines. Although CYP1A2 expression has been detected only in liver, 42 the absence of expression in other organs does not necessarily mean lack of activity, either directly within tissues and/or via feedback from extrahepatic sites.…”

Section: Discussionmentioning

confidence: 99%

Hyalinosis and Ym1/Ym2 Gene Expression in the Stomach and Respiratory Tract of 129S4/SvJae and Wild-Type and CYP1A2-Null B6,129 Mice

Ward

Yoon

Anver

et al. 2001

The American Journal of Pathology

128

129

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The C57BL/6, 129, and B6,129 mouse strains or stocks have been commonly used to generate targeted mutant mice. The pathology of these mice is not well characterized. In studies of these aging mice, we found high incidences of hyalinosis (eosinophilic cytoplasmic change) in the glandular stomach, respiratory tract, bile duct, and gall bladder of B6,129 CYP1A2-null and wild-type mice as well as in both sexes of the background 129S4/SvJae strain. The gastric lesions of the glandular stomach were found in 95.7% of female CYP1A2-null mice as well as in 45.7% of female 129S4/SvJae animals. The eosinophilic protein isolated from characteristic hyaline gastric lesions was identified as Ym2, a member of the chitinase family. Immunohistochemistry, using rabbit polyclonal antibodies to oligopeptides derived from the Ym1 sequence, detected focal to diffuse reactivity within both normal and abnormal nasal olfactory and respiratory epithelium, pulmonary alveolar macrophages, bone marrow myeloid cells, and the squamous epithelium of the forestomach and epithelium of the glandular stomach. Alveolar macrophages in acidophilic pneumonia, a major cause of death of aging 129 mice, and in mice with the me mutation also were highly immunoreactive. CYP1A2 carries out oxidation and N-hydroxylation of arylamine carcinogens and heterocyclic amine food mutagens which, when followed by O-esterification by acetate or sulfate transferases, results in unstable electrophilic derivatives that can cause cell toxicity, cell death, or cell transformation. 1-3 CYP1A2 catalyzes caffeine 3-demethylation and metabolically activates aflatoxin B 1 to its ultimate carcinogenic intermediate 4 and paradoxically catalyzing the hydroxylation of aflatoxin B 1 to aflatoxin M 1 in a detoxification pathway. 5 In addition, CYP1A2 was found to be involved in both hamster and human catechol estrogen metabolism. 6 Although CYP1A2 is constitutively expressed in the liver of mice, rats, and humans and is inducible by ligands of the aryl hydrocarbon receptor (Ahr) in all mammalian species analyzed, no expression has been demonstrated in the stomach, even after treating animals with known inducers of this enzyme. 7 However, the mechanisms involved in CYP1A2 gene regulation are less well established than CYP1A1 because it is difficult to induce expression in vitro and the sensitivities of current methodologies may simply be too low under normal in vivo conditions. The mammalian conservation of the CYP1A subfamily argues for an essential function in metabolism not limited to activation and detoxification of exogenous chemicals and toxins. As with most of the cytochromes P-450, determination of function has primarily been a consequence of exposures to man-made compounds, but it must be remembered that their evolution predates industrialization. The genes of the two recognized members of the CYP1A subfamily,

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Section: Discussionmentioning

confidence: 99%

Hyalinosis and Ym1/Ym2 Gene Expression in the Stomach and Respiratory Tract of 129S4/SvJae and Wild-Type and CYP1A2-Null B6,129 Mice

Ward

Yoon

Anver

et al. 2001

The American Journal of Pathology

128

129

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“…Also the increase in rat and rabbit liver alcohol-inducible P450IIE mRNA is insufficient to account for the increase in the amount of the corresponding protein and associated activities [30, 311. It has also been reported that the stability of cytochrome-P1-450 mRNA in mouse varies [32]. The observation was that the inducer enhances mRNA stability in some instances.…”

Section: Discussionmentioning

confidence: 86%

2‐(4′‐Chlorophenyl)benzothiazole is a potent inducer of cytochrome P450IA1 in a human and a mouse cell line

Kärenlampi¹,

Tuomi²,

Korkalainen³

et al. 1989

European Journal of Biochemistry

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Two benzothiazole derivatives, 2-(4'-chlorophenyl)benzothiazole (CPBT) and 2-(4'-formy1phenyl)benzothiazole (FPBT) were studied for their ability to induce aryl hydrocarbon hydroxylase activity in a mouse and a human cell line. In both the mouse hepatoma cell line, Hepa-1, and the human choriocarcinoma cell line, JEG-3, a high aryl hydrocarbon hydroxylase activity was observed after treatment with CPBT. In contrast, FPBT had a very weak inducing capacity in both cell lines. The maximal induction by CPBT was several times (e. g. in Hepa-1 about fourfold on average) greater than that observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A specific cDNA probe for mouse cytochrome P450IA1 gene was used to quantify mRNA levels in Hepa-I cells. CPBT increased cytochrome P450IA1 mRNA to a level of 88% of that induced by TCDD. Immunoblot analysis with monoclonal antibody 1-7-1, directed against rat liver cytochrome P450IA1 and P450iA2, showed that the amount of P450IA1 is substantially increased in Hepa-1 cells after treatment with CPBT. The observation that CPBT competed TCDD off its specific cytosolic binding site suggests a receptor-mediated induction of cytochrome P4501A1 mRNA. An in vitro activation effect did not explain the exceptionally high hydroxylase activity. The results show that CPBT is a more efficient inducer of aryl hydrocarbon hydroxylase than TCDD in Hepa-1 and JEG-3 cells and that the induction is supported by P4501A1. The discordant effect of CPBT on mRNA and aryl hydrocarbon hydroxylase activity suggests that post-translational modifications of P4501A1 account for a major part of the increased enzyme activity.Aryl hydrocarbon hydroxylase activity in mammalian liver is induced by several groups of compounds, including polycyclic hydrocarbons, phenothiazines, symmetrically substituted five-membered heterocyclis and flavones. Flavonoids have been shown to activate the oxidative drug metabolism both in vitro and in vivo [I]. These are compounds present naturally in herbaceous plants and certain citrus fruits. The human diet thus contains a complex mixture of flavonoids.Phenylbenzothiazoles have structurally some common features with flavonoids. A extensive study has been done on the structure/activity relationship of the inducing capacity of benzo[a]pyrene (aryl hydrocarbon) hydroxylase activity by 2-phenylbenzothiazoles [2]. The only substitutions which cause a pronounced increase in inducing activity are halogen substitutions into the 4'-phenyl position, e. g. introduction of a chloro substitution results in a pronounced increase in inducing capacity. In the rat the chloro derivative causes a 7.8-fold increase ic !iver and 6.4-fold increase in lung aryl hydrocarbon hydroxylase activity compared with untreated

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“…Pasco et al (1988) also reported that P-450d mRNA was not detected in the lung, even in the animals treated with high dose of TCDD. However, Kimura et al (1986) demonstrated the induction of P3 450-mRNA in the lungs of TCDD-treated mice by slot blot analysis probing with a 3'-specific portion of P3450 cDNA. TCDD is also known as a strong inducer of P-450c and P-450d in hepatic tissue.…”

Section: Resultsmentioning

confidence: 99%

“…Degawa et al (1987) and Goldstein and Linko (1984) demonstrated the absence of P-450d in the pulmonary tissue of MC-treated rats by the method of Western blot analysis. But Kimura et al (1986) showed the induction of P3450 (equivalent to rat P-450d) in the pulmonary tissue of MCtreated mice by the method of Northern hybridization.…”

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confidence: 99%

Complementary DNA sequence of 3-methylcholanthrene-inducible P-450 from the rat lung.

Kikuchi

Sagami²,

Fujii³

et al. 1990

Tohoku J. Exp. Med.

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Cytochrome P-450MC was induced in pulmonary microsomes of 3-methylcholanthrene-treated rats and also at low level in that of isosafrole-treated rats. Cytochrome P-450d was not detected in the lungs of 3-methylcholanthrene-or isosafrole-treated rats by the method of Western blot analysis with a polyclonal antibody raised against cytochrome P-450c which is equally effective against P-450d, nor by the method of Northern hybridization probed with pcP450mc3 (P-450d probe). Complementary DNA of P-450MC was isolated from rat pulmonary cDNA library and the nucleotide sequence of pulmonary cDNA was compared with that of hepatic P-450c cDNA reported by Yabusaki et al. There was no gross change in nucleotide sequences of cDNA between pulmonary P-450MC and hepatic P-450c. cytochrome P-450; cDNA cloning ; rat lung ; nucleotide sequence ; gene expression Cytochrome P-450s metabolize various exogenous and endogenous compounds (Nebert and Gonzalez 1987). Many P-450 isozyme types have been demonstrated to have the different substrate specificity and tissue distribution. Rat hepatic MC-inducible P-450 is involved in the hydroxylation of arylhydrocarbon carcinogens, including benzo(a)pyrene (Thakker et al. 1977).Received January 24, 1990; revision accepted for publication March 1, 1990. The abbreviations used are : MC, 3-methylcholanthrene ; ISF, isosafrole ; SDS, sodium dodecyl sulfate ; SSC, 0.15 M NaCI-0.015 M sodium citrate (pH 7.0) ; pfu, plaque forming unit ; TCDD,2,3,7, ; P-450c, hepatic cytochrome P-450(low spin type) of rats treated with MC ; P-450d, hepatic cytochrome P-450 (high spin type) of rats treated with MC ; An attempt to standardize the nomenclature of diverse P-450 isozymes has been made . P-450c and P-450d are termed P450IA1 and P450IA2, respectively. P-450MC denotes pulmonary cytochrome P-450 of rats treated with MC.

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Tissue-specific expression of the mouse dioxin-inducible P(1)450 and P(3)450 genes: differential transcriptional activation and mRNA stability in liver and extrahepatic tissues.

Cited by 170 publications

References 37 publications

Hyalinosis and Ym1/Ym2 Gene Expression in the Stomach and Respiratory Tract of 129S4/SvJae and Wild-Type and CYP1A2-Null B6,129 Mice

Hyalinosis and Ym1/Ym2 Gene Expression in the Stomach and Respiratory Tract of 129S4/SvJae and Wild-Type and CYP1A2-Null B6,129 Mice

2‐(4′‐Chlorophenyl)benzothiazole is a potent inducer of cytochrome P450IA1 in a human and a mouse cell line

Complementary DNA sequence of 3-methylcholanthrene-inducible P-450 from the rat lung.

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