Overexpression of Protein Tyrosine Phosphatase 1B in HepG2 Cells Ameliorates Insulin-mediated Suppression of Apolipoprotein B mRNA Translation Via Its Untranslated Regions
Bibliographic record
Abstract
Background: The hepatic secretion of apolipoprotein B (apoB), containing lipoproteins, is known to be regulated by insulin, and the overproduction of these atherogenic lipoproteins occurs in insulin-resistant states. Protein tyrosine phosphatase 1B (PTP-1B) is a key regulator of hepatic insulin signaling and is also upregulated in insulin resistance. We aimed to investigate the role of PTP-1B in regulating apoB mRNA translational efficiency mediated by 5’/3’ untranslated regions (UTRs) under conditions of insulin stimulation. Methods: Human hepatoma HepG2 cells were transfected with a vector carrying the firefly luciferase reporter gene and either a chimeric apoB mRNA encoding the 5’/3’ untranslated region (5’LUC3’-pGL3) or a null sequence of length equivalent to apoB 5’ UTR (LUC-pGL3). The transfected cells were then infected with adenovirus carrying the mouse PTP-1B gene (AdPTP1B) in the absence or presence of insulin, and the cellular luciferase activity was determined. The RNA extracts from cells were transfected with constructs carrying 5’/3’ apoB UTR, or a null sequence was also translated in vitro in a rabbit reticulocyte translation system. Results: The luciferase activity of the cells transfected with constructs containing the apoB UTR sequences (5’LUC3’) was significantly higher than that of the control constructs carrying a null sequence (p<0.01, n=12). Similar results were observed following in vitro translation studies showing a significantly higher expression of the 5’/3’ UTR constructs (p<0.001, n=6). Treatment with 100 nM insulin led to a significant reduction in the luciferase activity of the constructs carrying apoB 5’/3’ UTR (p<0.0001, n=12). The down regulation of the apoB mRNA translation mediated by insulin was mediated by the apoB 5’/3’ UTR sequences since insulin did not affect the control constructs containing a null sequence. The infection of HepG2 cells expressing 5’LUC3’ or control constructs with AdPTP-1B attenuated the inhibitory effect of insulin and led to higher levels of luciferase activity compared to the Ad-gal infected control cells (p< 0.05, n=12). However, the activity was lower than that in the control cells infected with 5’LUC3’-pGL3 but not treated with insulin (p<0.05, n=12). Conclusion: Our data suggest that PTP-1B can potentially modulate apoB synthesis by blocking insulin-mediated inhibition of the apoB mRNA translation via its 5’/3’ UTR sequences. We hypothesize that the PTP-1B-mediated attenuation of the insulin action can lead to the upregulation of the apoB mRNA translation and contribute to a lipoprotein overproduction in conditions such as insulin resistance.
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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 | 0.001 |
| 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".