Regulation of sucrase-isomaltase and hexose transporters in Caco-2 cells: a role for cytochrome P-4501A1?
Involvement of cytochrome P-4501A1 (CYP1A1) in the regulation of sucrase-isomaltase and hexose transporters was analyzed in low (TC7)- and high (PF11)-glucose-consuming Caco-2 clones. CYP1A1 mRNA is elevated in exponentially growing cells concomitantly with high rates of glucose consumption and high levels of GLUT-1 and GLUT-3 mRNA. After confluency, CYP1A1 is not detectable in TC7 cells; this is associated with a decreased glucose consumption, a downregulation of GLUT-1 and GLUT-3, and an upregulation of sucrase-isomaltase, SGLT-1, GLUT-2, and GLUT-5. In PF11 cells CYP1A1 mRNA remains elevated, along with high glucose consumption, high levels of GLUT-1 and GLUT-3, and minimal expression of sucrase-isomaltase, SGLT-1, GLUT-2, and GLUT-5. Exposure of TC7 cells to inducers of CYP1A1 results in high levels of CYP1A1 mRNA, a 10-fold increase of glucose consumption after confluency, an upregulation of GLUT-1 and GLUT-3, and a downregulation of sucrase-isomaltase, GLUT-2, and, to a lesser extent, SGLT-1 and GLUT-5. These results suggest that activation of CYP1A1, whether spontaneous or drug induced, is involved in the variations of glucose utilization and in the associated modifications of expression of sucrase-isomaltase and hexose transporters.
Carrière
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Unité de Recherches sur la Différenciation Cellulaire Intestinale, Institut National de la Santé, Villejuif, France.
Barbat
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A
Rousset
M
M
Brot-Laroche
E
E
Dussaulx
E
E
Cambier
D
D
De Waziers
I D
ID
Beaune
P
P
Zweibaum
A
A
D018938:Caco-2 Cells / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002999:Clone Cells; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism*
D007773:Lactates; D009004:Monosaccharide Transport Proteins; D019344:Lactic Acid; D003577:Cytochrome P-450 Enzyme System; D013394:Sucrase-Isomaltase Complex; D005947:Glucose