BNIP3 Regulation of Intracellular Calcium
Bibliographic record
Abstract
Necrotizing enterocolitis is the most common gastrointestinal emergency affecting low‐birth weight premature infants, with an incidence between 3% and 10% in infants less than 1500 grams, and mortality ranging from 15% to 30%. The pathogenesis of NEC is not clearly defined, but is likely a multifactorial disease wherein intestinal ischemia and hypoxia play fundamental roles. The hypoxia‐inducible death gene Bnip3 has been recently identified as a key regulator of NEC, yet the molecular mechanisms surrounding Bnip3‐induced enterocyte necrosis are not fully defined. Calcium‐mediated opening of the mitochondrial permeability transition pore (mPTP) has been identified as an important precursor event to necrotic cell death. Therefore, we tested the hypothesis that Bnip3 initiates calcium‐dependent PTP opening in cultured cells. We demonstrate that expression of Bnip3 increases mitochondrial calcium content, determined by Rhod2 staining, and that this effect is attenuated by expression of the inhibitory alternative splice variant Bnip3ΔEx3. Consistent with these findings, Bnip3 expression opens the mPTP, which was also prevented by Bnip3ΔEx3. Using organelle‐targeted calcium indicators, we found that Bnip3ΔEx3 did not inhibit Bnip3‐induced calcium release from the endoplasmic reticulum. However, Bnip3ΔEx3 expression re‐directed calcium release and promoted nuclear accumulation of calcium. These novel findings indicate that Bnip3ΔEx3 may protect cells from necrosis by promoting calcium‐dependent signaling pathways that converge on the nucleus, and provide a novel mechanism that may serve to protect enterocytes from hypoxic injury during NEC. Support or Funding Information Athabasca University Children's Hospital Research Institute of Manitoba Natural Sciences and Engineering Research Council of Canada
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
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".