Decrease of mRNA levels and biosynthesis of sucrase-isomaltase but not dipeptidylpeptidase IV in forskolin or monensin-treated Caco-2 cells.
Treatment for 48 h of differentiated, confluent Caco-2 cells with 2.5 10(-5) M forskolin or 10(-6) M monensin, which produces a significant decrease of the de novo biosynthesis of sucrase-isomaltase, does not change quantitatively the de novo biosynthesis of dipeptidylpeptidase IV. Western blot analysis and silver nitrate staining indicate that neither drug induces any modification in the steady state expression of these two brush border hydrolases. Northern blot analysis shows that the level of dipeptidylpeptidase IV mRNA does not change in treated as compared to control Caco-2 cells. In contrast, forskolin and monensin dramatically decrease the level of sucrase-isomaltase mRNA. These observations suggest a separate regulation of biosynthesis for sucrase-isomaltase and dipeptidylpeptidase IV in intestinal cells. The mechanisms responsible for such a difference are discussed. Among them, the role of glucose metabolism, which is perturbed by both drugs, appears to be of crucial importance.
Darmoul
D
D
Unité de Recherches sur la différenciation cellulaire intestinale, Institut National de la Santé et de la Recherche Médicale, U178, Villejuif, France.
Baricault
L
L
Sapin
C
C
Chantret
I
I
Trugnan
G
G
Rousset
M
M
D000230:Adenocarcinoma / Q000201:enzymology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013394:Sucrase-Isomaltase Complex / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D005576:Colforsin; D008985:Monensin; D000242:Cyclic AMP; D013394:Sucrase-Isomaltase Complex; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D005947:Glucose