Hypoxia and CYP1A1 induction-dependent regulation of proteins involved in glucose utilization in Caco-2 cells.
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 beta-naphthoflavone (beta-NF) and hypoxia on these parameters and expression of key enzymes of glucose metabolism. Both beta-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 beta-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.
Unité de Recherches sur la Différenciation Cellulaire Intestinale, Institut National de la Santé et de la Recherche Médicale, Villejuif, France.
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D018938:Caco-2 Cells / Q000378:metabolism*; D015687:Cell Hypoxia; D003035:Cobalt / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013394:Sucrase-Isomaltase Complex / Q000235:genetics / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D019344:Lactic Acid; D003035:Cobalt; D019324:beta-Naphthoflavone; D006003:Glycogen; D019363:Cytochrome P-450 CYP1A1; D013394:Sucrase-Isomaltase Complex; C018021:cobaltous chloride; D005947:Glucose