Regulation of Redox-Sensitive Signaling Pathways in Rat Primary Astrocytes Following Acrolein Exposure
Bibliographic record
Abstract
Lipid peroxidation leads to the formation of a number of by-products including acrolein. In brain from patients with Alzheimer's disease (AD), acrolein was found to be elevated in vulnerable regions. Astrocytes contribute to a variety of neuronal functions but the toxicity of acrolein in astroglial cells remains unknown. Using the rat primary astroglial cells, our results show that acrolein is toxic from 15 μM. Acrolein induced a biphasic effect on glutathione (GSH) levels with a depletion after 30 min of treatment followed by a progressive increase 24 hrs after exposure while the expression of γ-glutamyl-cysteine-synthase (γ-GCS) was induced. Protein carbonyls levels were significantly higher with all tested concentrations of acrolein. We have further investigated the effect of acrolein on the regulation of different redox-sensitive signaling pathways. A treatment with 20 μM of acrolein for 30 min activated NF-κB, Nrf2, and heme oxygenase-1 while after 24 hrs of exposure, their induction was observed with the subtoxic and toxic concentrations of acrolein except for NF-κB. Sirt-1 was also up-regulated after 24 hrs of exposure with acrolein. Acrolein also induced the phosphorylation of p66shc and of ERK1/2 after 30 min of treatment. Our results provide evidence that acrolein is a potent inducer of redox-sensitive pathways in astrocytes with a differential regulation after a short or a long term period of exposure to overcome cell death. Considering the crucial role of astrocytes in the brain, these results demonstrated that acrolein could disrupt neuronal functions and synaptic homeostasis by provoking dysfunctional or loss of astrocytes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".