Radiation‐induced apoptosis of oligodendrocytes and its association with increased ceramide and down‐regulated protein kinase B/Akt activity
Bibliographic record
Abstract
PURPOSE: Oligodendrocytes are cells responsible for myelination in the central nervous system and have been shown to undergo radiation-induced apoptosis. The roles of ceramide and protein kinase B/Akt (PKB/Akt) were assessed in radiation-induced apoptosis of oligodendrocytes in vitro. MATERIALS AND METHODS: Primary cultures of oligodendrocytes were established from neonatal rat brains and cell identity was assessed by immunohistochemistry. Apoptosis was assessed histologically according to its specific morphologic features using 4',6-diaminido-2-phenylindole, and by transferase-mediated deoxynucleotidyl transferase nick end-labelling staining. The ceramide level was measured using a diacyglycerol kinase assay, and PKB/Akt activity was determined using immunoblotting and a protein kinase assay. RESULTS: Ionizing radiation, C2-ceramide or wortmannin induced apoptosis in oligodendrocytes but not astrocytes. A rapid increase in ceramide was observed in oligodendrocytes after ionizing radiation. Monensin, an inhibitor of acid sphingomyelinase, reduced the apoptotic response in oligodendrocytes after ionizing radiation. Fumonisin B1, an inhibitor of ceramide synthase, showed no such effect in the cells. Radiation-induced apoptosis of oligodendrocytes was associated with a decrease in PKB activity, similar to that observed after treatment with C2-ceramide or wortmannin, but not after dihydro-C2-ceramide. Confocal microscopy revealed a loss of phosphorylated PKB immunostaining in the nucleus of apoptotic oligodendrocytes after ionizing radiation or C2-ceramide treatment. The level of phosphorylated FKHRL1, a transcription factor phosphorylated by PKB, decreased in irradiated oligodendrocytes. CONCLUSIONS: A ceramide-PKB-mediated signalling pathway might play a role in radiation-induced apoptosis of oligodendrocytes.
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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) | 0.001 | 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".