Novel 5‐lipoxygenase isoforms affect the biosynthesis of 5‐lipoxygenase products
Bibliographic record
Abstract
5-Lipoxygenase (5-LO) is the essential enzyme for the biosynthesis of leukotrienes, important mediators of inflammation. This study investigated whether variants of 5-LO exist in human leukocytes. 5-LO mRNA isoforms that are consistent with alternative splicing were identified by RT-PCR in a cell line or cell type-specific pattern. All evaluated cells expressed mRNA containing all 14 exons of 5-LO with the expected splicing sites. Individual isoforms that retained intron 10 (α-10), lacked exon 13 (Δ-13), and lacked exons 10 and 13 (Δ-10,13) or that lacked the first 96 base pairs of exon 10 (Δ-p10) were identified. Immunoreactive bands coeluting with the cloned α-10 and Δ-13 isoforms were measured in primary neutrophils and in Raji cells. When expressed in HEK293 cells, alternative proteins were without catalytic activity. However, when coexpressed with the active full-length 5-LO, alternative isoforms significantly decreased the biosynthesis of 5-LO products by up to 44%, as assessed by reverse-phase HPLC analysis. Additionally, in stimulated neutrophils the full-length active 5-LO was detected by immunoblot in both nuclear and non-nuclear compartments, while the Δ-13 isoform was only detected in the nuclear fraction. These alternative 5-LO isoforms may represent a new mechanism for the regulation of the 5-LO pathway and lipid mediator biosynthesis.
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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".