Endoplasmic Reticulum Stress Mediated Inflammation may involve in Doxorubicin‐induced Cardiomyopathy
Bibliographic record
Abstract
Many subcellular signaling pathways have been proposed to explain myocardial dysfunction triggered by doxorubicin (Dox). Although endoplasmic reticulum (ER) stress has been suggested to be an important factor in myocardium dysfunction, its role in Dox‐induced cardiomyopathy (DIC) has not been fully understood. Here, we show that ER stress promotes inflammation through iNOS‐regulated Toll‐like receptor 2 (TLR 2) activation in DIC. Cardiomyopathy in male Wistar rats was produced by repeat six equal injections of Dox (each 2.5 mg/kg ip) over three weeks for a cumulative dose of 15 mg/kg body wt. Controls were given only saline. Hearts from these animals were used two weeks after the last treatment. ER stress in the DIC hearts was indicated by an upregulation of binding immunoglobulin proteins (Bip). Furthermore, there was an increased unfolded protein response and dimerization of Bip with ATF6. This increase in ER stress in DIC promoted iNOS activity. The latter was associated with increased expression of TLR2 and TRAF2 together with increased NFκB105/50 expression. This in‐turn promoted pro‐inflammatory cytokines TNF‐ α, and IL‐1α in the myocardium. Overall these data indicate that inflammation, mediated by ER stress, via a direct interaction of Bip and ATF6, upregulates iNOS as well as pro‐inflammatory cytokine production in DIC. Manipulation of this complex signaling pathway may be of therapeutic benefit to prevent cardiomyopathy due to Dox. Support or Funding Information Supported by CIHR and Research Manitoba This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".