RT Journal Article
SR Electronic
T1 Inhibition of Asparagine-linked Glycosylation Participates in Hypoxia-induced Down-regulation of Cell-surface MICA Expression
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1353
OP 1359
VO 38
IS 3
A1 NAOKO YAMADA
A1 NAHOKO KATO-KOGOE
A1 KOJI YAMANEGI
A1 HIROSHI NISHIURA
A1 YUKI FUJIHARA
A1 SHIGEO FUKUNISHI
A1 HARUKI OKAMURA
A1 NOBUYUKI TERADA
A1 KEIJI NAKASHO
YR 2018
UL http://ar.iiarjournals.org/content/38/3/1353.abstract
AB Background/Aim: Hypoxia down-regulates the expression of cell surface major histocompatibility class I-related chain molecule A (MICA) without increasing its shedding. Recently, the inhibition of N-linked glycosylation was also shown to reduce the cell-surface expression of MICA. We investigated the participation of asparagine (Asn)-linked glycosylation in hypoxia-induced down-regulation of cell-surface MICA using osteosarcoma cells. Materials and Methods: The cell-surface expression and Asn-N-glycosylation of MICA were estimated by flow cytometry, and western blot analyses, respectively. Results: Hypoxia reduced the expression of N-linked glycosylated MICA, as well as the ratio of N-linked glycosylated to non-glycosylated MICA. 2-Deoxy-D-glucose, which inhibits N-linked glycosylation, reduced the cell-surface expression of MICA under normoxia, while D-Mannose increased N-glycosylated MICA, increasing cell-surface MICA under hypoxia. Cells transfected with wild-type MICA expression vector expressed cell surface MICA more than those transfected with mutant MICA expression vectors designed for abrogation of N-linked glycosylation. Conclusion: The inhibition of Asn-N-linked glycosylation participates in hypoxia-induced down-regulation of cell-surface expression of MICA.