The modulation of abcb4 and cyp3a65 gene expression and multidrug/multixenobiotic resistance (MDR/MXR) functional activity in the model teleost, Danio rerio (zebrafish)
Bibliographic record
Abstract
The multidrug/multixenobiotic resistance (MDR/MXR) mechanism is a cellular response involving the induction and coordinated action of the ATP-binding cassette (ABC) transporter, P-glycoprotein (P-gp), and the phase I metabolizing enzyme, cytochrome P450 3A (CYP3A), which confers protection against potentially cytotoxic exposures of various drugs and environmental contaminants.In mammals, ligandmediated pregnane X receptor (PXR) transcriptional activity regulates the induction of Pgp and CYP3A but this mechanism is not well characterized in fish species.In this study, zebrafish treated with the Pxr (PXR) agonist PCN co-modulated P-gp (Abcb4) and CYP3A (Cyp3a65) mRNA expression and this co-modulation was associated with increased hepatic MDR/MXR functional activity in vivo.Consistent with a mammalianlike MDR/MXR mechanism regulated by PXR, zebrafish co-treated with PCN and the mammalian PXR antagonist, ketoconazole (KTC) attenuated the PCN-mediated modulation of hepatic abcb4 and cyp3a mRNA levels, as well as attenuated the PCNmediated modulation of MDR/MXR functional activity.These results suggest abcb4 may be involved with the MDR/MXR response in the adult zebrafish liver, and that Pxr (PXR) may regulate this dynamic process.Finally, the lack of Cyp3c1 mRNA modulation by PCN suggests that Cyp3c1 and Cyp3a65 may be regulated by separate transcriptional pathways.
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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 | 0.000 |
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".