원문정보
초록
영어
In general the extent of protein O-GlcNAc modification (O-GlcNAcylation) decreases when cellular glucose concentrations fall below normal levels. However, recent reports demonstrated that O-GlcNAcylation was increased by glucose deprivation in HepG2 and Neuro-2a cells. Here, we report increased O-GlcNAcylation in non-small cell lung carcinoma A549 cells and various cells in response to glucose deprivation. Although the level of O-GlcNAc transferase was not changed, it contained less O-GlcNAc and the activity was increased. Also, the activity of O-GlcNAcase was reduced. The studied glycogen containing cells, and we show that its degradation by glucose deprivation provides a source for UDP-GlcNAc required for increased O-GlcNAcylation under this condition. This required active glycogen phosphorylase and resulted in increased glutamine:fructose-6-phosphate amidotransferase, the first and rate-limiting enzyme in the hexosamine biosynthetic pathway. Interestingly, glucose deprivation reduced the amount of phosphofructokinase 1, a regulatory glycolytic enzyme, and blocked ATP synthesis. These findings suggest that glycogen is the source for increased O-GlcNAcylation but not for generating ATP in response to glucose deprivation and it may be useful for cancer cells to survive.