Effect of altered lipid homeostasis on cytochrome P450 2A5 expression
Bibliographic record
Abstract
Unlike most cytochrome P450 (CYP) enzymes, murine hepatic CYP2A5 and human CYP2A6 are elevated during hepatitis, fasting, and chemically‐induced hepatotoxicity. Since these enzymes metabolize nicotine and can activate pro‐carcinogens, their upregulation could affect tobacco addiction and carcinogenesis. However, the stimulus responsible for their induction remains unclear. Since CYP2A5 upregulation is usually associated with liver dysfunction, we hypothesized that a pathophysiological change associated with hepatotoxicity regulates CYP2A5 expression. This study examined the role of altered lipid homeostasis in CYP2A5 regulation. C57Bl6 mice were treated with saline or the hepatotoxin pyrazole for 24 hours, and hepatic gene transcripts were analyzed by Affymetrix microarray. Differential expression was observed for 109 genes associated with lipid synthesis, metabolism, and transport, confirming pyrazole alters lipid homeostasis. Furthermore, treatment of primary mouse hepatocytes with hepatic lipid extracts significantly increased CYP2A5 mRNA levels three‐fold. Analysis of hepatic fatty acid profiles indicated a significant elevation of linolenic acid in pyrazole‐treated mice that was absent in tetracycline‐treated animals which had no increase in CYP2A5 level. Ongoing work is investigating a role for linolenic acid in the regulation of CYP2A5. Funded by NSERC and CIHR.
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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".