Up-regulation of O-GlcNAc Transferase with Glucose Deprivation in HepG2 Cells Is Mediated by Decreased Hexosamine Pathway Flux
Bibliographic record
Abstract
O-Linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of proteins that functions as a nutrient sensing mechanism. We have previously shown a significant induction of O-GlcNAc modification under conditions of glucose deprivation. Increased O-GlcNAc modification was mediated by increased mRNA for nucleocytoplasmic O-linked N-acetylglucosaminyltransferase (ncOGT). We have investigated the mechanism mediating ncOGT induction with glucose deprivation. The signal does not appear to be general energy depletion because no differences in AMP-dependent kinase protein levels or phosphorylation were observed between glucose-deprived and normal glucose-treated cells. However, treatment of glucose-deprived cells with a small dose (1 mm) of glucosamine blocked the induction of ncOGT mRNA and subsequent increase in O-GlcNAc protein modification, suggesting that decreased hexosamine flux is the signal for ncOGT up-regulation. Consistent with this, treatment of glucose-deprived cells with an inhibitor of O-GlcNAcase (O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamat) completely prevented the subsequent up-regulation of ncOGT. Glucosamine treatment also resulted in a 40% rescue of the down-regulation of glycogen synthase activity normally seen after glucose deprivation. We conclude that deglycosylation of proteins within the first few hours of glucose deprivation promotes ncOGT induction. These findings suggest a novel negative feedback regulatory loop for OGT and O-GlcNAc regulation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".