Hypoxia and CYP 1 A 1 induction-dependent regulation of proteins involved in glucose utilization in Caco-2 cells

Carrière, Véronique,Annie Rodolosse, Michel Lacasa, Danièle Cambier, Alain Zweibaum, and Monique Rousset. Hypoxia and CYP1A1 induction-dependent regulation of proteins involved in glucose utilization in Caco-2 cells. Am. J. Physiol. 274 (Gastrointest. Liver Physiol. 37): G1101–G1108, 1998.—Although induction of cytochrome P-450 1A1 (CYP1A1) in the Caco-2 clone TC7 alters glucose utilization and modifies the expression of sucrase-isomaltase (SI) and hexose transporters, nothing is known of the events that control these effects. In this study, we analyzed the effects of b-naphthoflavone (b-NF) and hypoxia on these parameters and expression of key enzymes of glucose metabolism. Both b-NF and hypoxia induce similar changes: 1) induction of CYP1A1 mRNA; 2) increased glucose consumption and lactic acid production and lower glycogen content; 3) downregulation of SI and upregulation of GLUT1 mRNAs; 4) downregulation of fructose-1,6-bisphosphatase and pyruvate kinase mRNAs and upregulation of phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase, lactate dehydrogenase, and phosphofructokinase mRNAs; and 5) upregulation of c-fos and c-jun mRNAs. Although addition of inhibitors of CYP1A1 catalytic activity to b-NF-treated cells totally inhibits the enzyme activity, it does not modify CYP1A1 mRNA response and associated effects, thus excluding a direct role for the enzyme per se. These results point to a possible physiological implication of the signal-transduction pathway responsible for CYP1A1 induction.