Selective killing induced by an inhibitor of N-linked glycosylation.
Treatment with a low dose (0.5 microgram/ml) of tunicamycin (an inhibitor of N-linked glycosylation) blocked the cell cycle progression of both normal Balb/c 3T3 cells (A31) and their SV40-transformed derivatives (SVA31) specifically in early G1 (0-3 h after mitosis). Upon release after an 8-h treatment the A31 cells returned to the cell cycle via a 9-h recovery phase, indicating that they were arrested in G0. The A31 cells were fully viable after this treatment. In contrast, the postmitotic SVA31 cells, which were unable to arrest in G0, did not divide after the removal of tunicamycin. Instead, these cells died but this did not occur until 22-34 h after release from the treatment. SVA31 cells that had passed the postmitotic phase of G1 survived during the parental generation and divided normally. However, a large portion of these cells died during the next cycle, and in total during a 48-h period approximately 50% of the cells were killed as a consequence of an 8-h exposure to tunicamycin. In contrast, treatment with inhibitors of protein synthesis and HMG CoA reductase activity as well as inhibitors of modification of N-linked oligosaccharide chains did not result in cell death.
Larsson
O
O
Department of Tumor Pathology, Karolinska Hospital, Stockholm, Sweden.
Carlberg
M
M
Zetterberg
A
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis*; D006031:Glycosylation / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007212:Indolizines / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013539:Simian virus 40; D017026:Swainsonine / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology*; D054836:Indolizidines
D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007212:Indolizines; D009844:Oligosaccharides; D011500:Protein Synthesis Inhibitors; D017026:Swainsonine; D014415:Tunicamycin; C037806:castanospermine; D054836:Indolizidines