Inhibition of the post-translational processing of microvillar hydrolases is associated with a specific decreased expression of sucrase-isomaltase and an increased turnover of glucose in Caco-2 cells treated with monensin.
The biosynthesis and post-translational processing of sucrase-isomaltase and dipeptidylpeptidase IV were studied by L-[35S]methionine labeling, immunoisolation with monoclonal antibodies and SDS-PAGE in post-confluent Caco-2 cells treated with monensin (10 microM, 48 h). In addition to its classical effect on the post-translational processing of both hydrolases, i.e. an inhibition of the conversion of the high-mannose to the complex glycosylated form of the enzymes, monensin was found to have two other effects: a marked decrease of sucrase-isomaltase expression, but not of dipeptidylpeptidase IV; an increased turnover of glucose, as substantiated by increased rates of glucose consumption and lactic acid production and a decreased glycogen content. Whether these two effects are related to the particular differentiation and metabolic status of Caco-2 cells is discussed, as well as a possible role for the drug-induced modifications of glucose turnover on the decreased expression of sucrase-isomaltase.
D002460:Cell Line; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology*; D007773:Lactates / Q000096:biosynthesis; D008871:Microvilli / Q000201:enzymology; D008985:Monensin / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000096:biosynthesis*; D010779:Photofluorography; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D013394:Sucrase-Isomaltase Complex / Q000096:biosynthesis* / Q000235:genetics
D007773:Lactates; D009097:Multienzyme Complexes; D006003:Glycogen; D008985:Monensin; D006867:Hydrolases; D013394:Sucrase-Isomaltase Complex; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D005947:Glucose