RAGE availability lessens the degree of dysfunctional mitochondrial bioenergetics following chronic secondhand smoke exposure
Bibliographic record
Abstract
The receptor for advanced glycation end products (RAGE) is an immunoglobulin-type receptor abundantly expressed by lung parenchyma that coordinates inflammatory responses. We have previously described roles for RAGE following exposure to tobacco smoke (both primary and secondhand) and environmental diesel particulate matter. While inflammatory signaling, tissue remodeling, and pulmonary function have each been investigated, mitochondrial fitness that may underpin cellular health has not been characterized in a chronic exposure model. The current study assessed mitochondrial bioenergetics in RAGE knock out (RKO) and wild type (WT) mice exposed to 3 months of secondhand smoke (SHS) via a nose-only delivery system (Sireq Scientific, Montreal, Canada) or room air (RA). Select mice were also co-administered SHS and semi-synthetic glycosaminoglycan ethers (SAGEs) that inhibit RAGE/ligand interactions. We discovered that mitochondrial respiration was significantly decreased in WT+SHS mice compared to WT+RA following the addition of glutamate/malate, ADP, succinate, and FCCP. Each of these sequential substrates revealed less severe mitochondrial respiration compromise in RKO +SHS compared to WT+SHS mice, suggesting the absence of RAGE was sufficient to blunt waning mitochondrial fitness. Importantly, mitochondrial respiration was significantly improved in WT+SHS+SAGEs mice compared to WT+SHS mice. These results provide a snapshot of mitochondrial fitness following chronic SHS exposure and suggest a role for RAGE signaling in altering cellular bioenergetics during exposure. This work was supported by funding from the National Institutes of Health (NIH 1R15-HL152257, PRR and JAA). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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 | 0.001 |
| 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".