Role of iPLA₂ in complement (C5b-9) mediated GEC injury
Bibliographic record
Abstract
There are a number of isoforms in the PLA2 superfamily, including secretory PLA2s (sPLA2) cytosolic PLA2s (cPLA 2), and calcium independent PLAS (iPLA2beta-short, beta-long, and gamma). In membranous nephropathy, glomerular epithelial cell (GEC) injury by complement C5b-9 leads to morphological changes in GEC and proteinuria, in association with cPLA2alpha activation. The present study addresses the role of iPLA2 in GEC injury. Complement-mediated release of [3H] arachidonic acid was most significantly augmented in GEC overexpressing iPLA2gamma (GEC-iPLA2gamma) as compared with GEC-Neo control. The accelerated AA release was inhibited by the iPLA2-directed catalytic inhibitor bromoenol lactone (BEL). For comparison, GEC-iPLA2gamma also amplified [3H]AA release after incubation of GEC with H2O2, or chemical anoxia followed by re-exposure to glucose, whereas stable clones overexpressing iPLA2gamma only amplified [3H]AA release after incubation with H2O2. Complement-mediated cytotoxicity (measured by release of lactate dehydrogenase) was attenuated significantly in GEC-iPLA2gamma, as compared with GEC-Neo, and the cytoprotective effect of iPLA2gamma was reversed by BEL and partially by Indomethacin. In keeping with previous results, incubation of GEC-cPLA2alpha with complement increased free [3H]AA. This increase in [ 3H]AA was blocked by BEL, although BEL did not block cPLA2alpha activity in cell extracts in vitro. Thus, in addition to cPLA2alpha, iPLA2gamma may be involved in complement-mediated release of AA. Moreover, activation of cPLA2alpha by complement appears to be, at least in part, dependent on iPLA2gamma. Modulation of iPLA2gamma activity may provide a new approach to reducing GEC injury.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".