Autophagic degradation of N-linked glycoproteins is downregulated in differentiated human colon adenocarcinoma cells.
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.
Houri
J J
JJ
INSERM U239, Unité de Recherche sur la Biologie et la Physiopathologie des Cellules Digestives, Paris, France.
Ogier-Denis
E
E
Trugnan
G
G
Codogno
P
P
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
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