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 3 4 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 fus ion studies to be linked to the glycosylation phenotype. In some of th e 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 in duced apoptosis, as determined by appearance of DNA fragmentation. Tun icamycin (TRI) also induced apoptosis in both parental and Lec9 cells. There was a direct correlation between inhibition of glycosylation by TRI treatment and induction of apoptosis. Induction of apoptosis by T M was inhibited by cycloheximide. These studies suggest that specific alterations in N-linked glycosylation in CHO cells are endogenous indu cers of apoptosis. (C) 1998 Academic Press.