title: Removal of N-glycans from cell surface proteins induces apoptosis by reducing intracellular glutathione levels in the rhabdomyosarcoma cell line S4MH.
abstract: Expression of determined Asn-bound glycans (N-glycans) in cell surface glycoproteins regulates different processes in tumour cell biology. Specific patterns of N-glycosylation are displayed by highly metastatic cells and it has been shown that inhibition of N-glycan processing restrains cell proliferation and induces cell death via apoptosis. However, the mechanisms by which different N-glycosylation states may regulate cell viability and growth are not understood. Since malignant cells express high levels of intracellular glutathione (GSH) and a reduction of intracellular GSH induces cell death via apoptosis, we investigated whether GSH was involved in the induction of apoptosis by removal of cell surface N-glycans. We found that removal of N-glycans from cell surface proteins by treating the rhabdomyosarcoma cell line S4MH with tunicamycin or N-glycosidase resulted in a reduction in intracellular GSH content and cell death via apoptosis. Moreover, GSH depletion caused by the specific inhibitor of GSH synthesis BSO induced apoptosis in S4MH cells. This data indicates that adequate N-glycosylation of cell surface glycoproteins is required for maintenance of intracellular GSH levels that are necessary for cell survival and proliferation.
authors.affiliation: Department of Cell Biology and Morphological Sciences, School of Medicine and Odontology, University of the Basque Country, Leioa, Vizcaya, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Calle
authors.forename: T
authors.initials: T
authors.lastname: Palomares
authors.forename: B
authors.initials: B
authors.lastname: Castro
authors.forename: M
authors.initials: M
authors.lastname: del Olmo
authors.forename: A
authors.initials: A
authors.lastname: Alonso-Varona
mesh_terms: D000581:Amidohydrolases / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000172:deficiency*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011134:Polysaccharides / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D014415:Tunicamycin; D019328:Buthionine Sulfoximine; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D005978:Glutathione