Monensin inhibits the expression of sucrase-isomaltase in Caco-2 cells at the mRNA level.
Using L-[35S]methionine labeling, SDS-PAGE and Northern blot analysis of sucrase-isomaltase mRNA, two different concentrations of monensin were used to delineate in Caco-2 cells the effect of the drug on the conversion of the high mannose to the complex form of sucrase-isomaltase from its dual effect on the biosynthesis of the enzyme and on the rate of glucose consumption. At 0.1 microM the drug has no effect on the rate of glucose consumption and, although it inhibits the conversion of the high mannose to the complex form of the enzyme, it has no effect on the level of sucrase-isomaltase mRNA and on the amount of neosynthesized enzyme. At 1 microM, in addition to its inhibiting effect on the maturation of the enzyme, monensin provokes concomitantly an increase in the rate of glucose consumption and a decrease in the level of sucrase-isomaltase mRNA and in the amount of neosynthesized enzyme. All these effects are reversible within 48 h after removal of the drug.
Chantret
I
I
Unité de Recherches sur la Différenciation et la Neuroendocrinologie de Cellules Digestives, INSERM U178, Villejuif, France.
Trugnan
G
G
Dussaulx
E
E
Zweibaum
A
A
Rousset
M
M
D003110:Colonic Neoplasms / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008358:Mannose / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D013394:Sucrase-Isomaltase Complex / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D008985:Monensin; D013394:Sucrase-Isomaltase Complex; D005947:Glucose; D008358:Mannose