A functional link between N-linked glycosylation and apoptosis in Chinese hamster ovary cells.
Seven different Chinese hamster ovary (CHO) cell mutants, isolated in different ways and having biochemical defects that were expressed at 34 degrees C, were found to be temperature sensitive for growth at 40.5 degrees C. Six of the mutants had five different lesions in N-linked glycosylation; two mutants were in the same complementation group. The temperature-sensitive phenotype in three mutants appeared by cell fusion studies to be linked to the glycosylation phenotype. In some of the glycosylation mutants [B4-2-1 (Lec15.1), Lec9, Lec1, and Lec24], but not in all of them (MI5-4 and MI8-5), incubation at 40.5 degrees C induced apoptosis, as determined by appearance of DNA fragmentation. Tunicamycin (TM) also induced apoptosis in both parental and Lec9 cells. There was a direct correlation between inhibition of glycosylation by TM treatment and induction of apoptosis. Induction of apoptosis by TM was inhibited by cycloheximide. These studies suggest that specific alterations in N-linked glycosylation in CHO cells are endogenous inducers of apoptosis.
Walker
B K
BK
Department of Biochemistry, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 20205, USA.
Lei
H
H
Krag
S S
SS
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016466:CHO Cells / Q000378:metabolism / Q000473:pathology*; D006224:Cricetinae; D006031:Glycosylation; D009154:Mutation