Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity
Bibliographic record
Abstract
Under endoplasmic reticulum (ER) stress (ERS), cells initiate the unfolded protein response (UPR) to maintain ER homeostasis. Recent studies revealed ERS transmission between cells and tissues, by activating the cell-nonautonomous UPR in cells that do not experience ERS directly. Here, we report that ERS triggers a rapid release of ceramide independent of the UPR, but requiring the acid sphingomyelinase activity. Carried by lipoproteins, ceramide is delivered to receiving cells to induce the UPR and regulate cell functions at multiple aspects, including lipid accumulation, cell death, and cytokine production. Mechanistically, extracellular ceramide stimulates ceramide synthesis at the transcription level in receiving cells, leading to ceramide accumulation in the ER so as to reduce membrane fluidity to disrupt ER calcium homeostasis, thus activating the UPR. Sphingomyelin counterbalanced the effect of ceramide. UPR induction is the frontline response to protect cells from ceramide insult. Our study suggests ceramide-mediated ERS transmission as a universal cell-cell communication model regulating a wide range of physiological events.
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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 | 0.001 |
| Open science | 0.000 | 0.001 |
| 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".