Removal of N-glycans from cell surface proteins induces apoptosis by reducing intracellular glutathione levels in the rhabdomyosarcoma cell line S4MH

Biol Cell. 2000 Dec;92(8-9):639-46. doi: 10.1016/s0248-4900(01)01114-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Buthionine Sulfoximine / pharmacology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • DNA Damage / drug effects
  • DNA Damage / physiology
  • Enzyme Inhibitors / pharmacology
  • Glutathione / deficiency*
  • Humans
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism*
  • Membrane Glycoproteins / drug effects*
  • Membrane Glycoproteins / metabolism
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / physiopathology
  • Neoplasm Metastasis / prevention & control
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Polysaccharides / metabolism*
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / metabolism
  • Rhabdomyosarcoma / physiopathology
  • Tumor Cells, Cultured / drug effects*
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Tunicamycin / pharmacology


  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Membrane Glycoproteins
  • Polysaccharides
  • Tunicamycin
  • Buthionine Sulfoximine
  • Amidohydrolases
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Glutathione