title: Autophagic degradation of N-linked glycoproteins is downregulated in differentiated human colon adenocarcinoma cells.
abstract: The aim of the present study was to elucidate the mechanism responsible for the high mannose glycoprotein instability in undifferentiated HT-29 cells (a human colon cancer cell line) reported previously. The results presented here are consistent with lysosomal degradation of these molecular species. In addition inhibitors of the autophagic-lysosomal degradative pathway (3-methyladenine, okadaic acid and asparagine) dramatically block the degradation of proteins and N-linked glycoproteins in undifferentiated HT-29 cells. The main conclusions of this work are: 1- the autophagic-lysosomal pathway is responsible for the high mannose glycoprotein degradation in undifferentiated HT-29 cells; 2- this degradative pathway exists in differentiated cells but is greatly reduced (3.5-4 fold); 3- the HT-29 cell line is a new model to investigate the molecular regulation of autophagy.
authors.affiliation: INSERM U239, Unité de Recherche sur la Biologie et la Physiopathologie des Cellules Digestives, Paris, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Houri
authors.forename: E
authors.initials: E
authors.lastname: Ogier-Denis
authors.forename: G
authors.initials: G
authors.lastname: Trugnan
authors.forename: P
authors.initials: P
authors.lastname: Codogno
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism*; D001216:Asparagine / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D019319:Okadaic Acid; D011134:Polysaccharides / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D002250:Carbon Radioisotopes; D002273:Carcinogens; D004988:Ethers, Cyclic; D006023:Glycoproteins; D011134:Polysaccharides; D014316:Tritium; D019319:Okadaic Acid; C025946:3-methyladenine; D001216:Asparagine; D002738:Chloroquine; D007930:Leucine; D000225:Adenine; D008358:Mannose