Exposure to cigarette smoke disrupts the molecular regulation of mitochondrial metabolism in epithelial cells of the human airways
Bibliographic record
Abstract
Exposure of the human airways to cigarette smoke (CS) is the major etiological risk factor for developing devastating lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). Although previous studies demonstrated aberrant mitochondrial morphology and impaired mitochondrial function in response to exposure of human airway epithelial cells to CS, to what extent the pathways regulating mitochondrial content and quality control are impacted is unknown. Therefore, we assessed the activity and abundance of key constituents of mitochondrial metabolic pathways, as well as transcript and protein levels of critical molecules regulating mitochondrial biogenesis and mitophagy in undifferentiated human primary bronchial epithelial cells (PBECs; provided by PLUC facility MUMC+, Maastricht) of COPD (n=5) and non-COPD (n=7) subjects, in undifferentiated PBECs of non-COPD subjects (n=4) exposed to CS extract (CSE) (0-1-2%), and in air-liquid interface differentiated PBECs of non-COPD subjects (n=4) exposed to CS (1 Marlboro Red cigarette) by machine smoking according to the Health Canadian Intense Regime. Evaluation of the abundance of prominent regulators controlling mitochondrial metabolic pathways revealed no outstanding differences at gene and protein level in PBECs of COPD versus non-COPD subjects. Although mitochondrial DNA copy number was unaltered, CSE exposure, dose- and time-dependently, downregulated mRNA levels of mitochondrial biogenesis markers and upregulated protein and transcript abundance of autophagy regulators in undifferentiated PBECs. Moreover, we observed increased metabolic enzyme activity in response to CSE exposure, respectively of hydroxyacyl-coenzyme A dehydrogenase and phosphofructokinase. These alterations were, at least in part, recapitulated in CS exposed differentiated PBECs. Collectively, these data show that CS(E) exposure disrupts the molecular regulation of mitochondrial metabolism in cells of the human airways.
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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) | 0.001 | 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".