Decreased expression of gamma-glutamyltranspeptidase in the intestinal cell line Caco-2 by inducers of cytochrome P450 1A1.
Our purpose was to investigate whether inducers of cytochrome P450 1A1 (CYP1A1), which cause a decreased expression in Caco-2 cells, at both the mRNA and protein levels, of membrane proteins associated with the uptake and transport of hexoses, would also affect the expression of gamma-glutamyltranspeptidase (gammaGT) (EC 2.3.2.2). In Caco-2 clonal TC7 cells grown under standard conditions (25 mM glucose), exposure to beta-naphthoflavone (beta-NF), 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 3-methylcholanthrene resulted in increased glucose consumption and decreased gammaGT activity in cells grown to confluence, i.e. when the differentiation is optimum. GammaGT activity was further analyzed during the time course of differentiation of TC7 cells treated or not with beta-naphthoflavone: while gammaGT activity in untreated cells showed a 10-fold increase from the exponential phase of growth until late postconfluence, gammaGT activity in beta-NF-treated cells, although increasing by 4-fold, remained at a much lower level (<25%). This decreased activity of gammaGT was associated with a decreased level of gammaGT mRNA. This inhibiting effect was not dependent on the CYP1A1 activity, as it also occurred in the presence of CYP1A1 inhibitors such as alpha-naphthoflavone, 8-methoxypsoralen or ellipticin. It was however dependent on glucose supply as it was not observed when the cells were cultured in low glucose (1 mM). These results raise the question of whether, in Caco-2 cells, CYP1A1 inducers or the signal transduction system which controls CYP1A1 are involved in the regulation of the expression of gammaGT through a mechanism involving glucose metabolism.
Unité de Recherches sur la Différenciation Cellulaire Intestinale, INSERM U178, Villejuif, France.
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Carrière
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Dussaulx
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Rousset
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Zweibaum
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Cambier
D018938:Caco-2 Cells; D002384:Catalysis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005947:Glucose / Q000502:physiology; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology; D013997:Time Factors; D019324:beta-Naphthoflavone / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis* / Q000235:genetics
D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D005723:gamma-Glutamyltransferase; D005947:Glucose