Autophagy and Heat Shock Protein 70 Expression During Acute Heat Stress in Isosmotic and Hyperosmotic Conditions in Peripheral Blood Mononuclear Cells from Young Adults: Preliminary Data
Bibliographic record
Abstract
Heat‐stress induced dehydration is associated with elevations in extracellular osmolality. To counteract the resultant osmotic stress, cells employ several stress response systems including the heat shock protein (HSP) and autophagy pathways. HSPs refold damaged proteins, whereas autophagy acts to degrade damaged cellular components, thereby promoting cellular survival. Accumulating evidence indicates a coordinated response between the HSP and autophagy systems, whereby both systems are activated under conditions of heat stress. However, it remains unknown whether elevated extracellular osmolality augments the HSP and autophagic response to whole‐body heat stress in humans. Thus, the purpose of this study was to examine changes in HSP (HSP70) and autophagy resulting from elevated intravascular osmolality during acute heat exposure. We hypothesized that both autophagy and HSP70 protein expression would be greater under hyperosmotic stress compared to isosmotic conditions. On separate days (separated by ~1 week), six young men (mean [SD]; 27 [5] years) received a 90‐min intravenous infusion with either isosmotic (ISO; 0.9% NaCl; 0.200 mL·kg −1 ·min −1 ) or hyperosmotic (HYP; 3.0% NaCl; 0.125 mL·kg −1 ·min −1 ) saline, followed by passive whole‐body heating to ~0.8°C above baseline esopha‐‐‐geal temperature using a water perfused suit. Serum osmolality was determined via freeze‐point depression from blood samples at baseline and at the end of passive heating. Peripheral blood mononuclear harvested at these time‐points were analyzed via Western blotting to assess changes in HSP70 protein and proteins indicative of autophagic activity including microtubule associated protein 1 light chain 3 beta‐II (LC3‐II) and p62/sequesterome‐1 (p62). All values were normalized to β‐actin and reported as fold changes relative to baseline. Data are presented as means and standard deviations (SD) and were compared between‐conditions at the end of passive heating using paired (2‐tailed) t‐tests (α=0.05). At the end of heating, serum osmolality was higher during HYP when compared to ISO (298 [SD 3] vs. 291 [SD 3]; p<0.001). During passive heating, LC3‐II was increased (2.20 [SD 2.12] vs. 1.62 [SD 1.47]; p=0.04) and p62 protein was reduced (0.47 [SD 0.33] vs. 1.20 [SD 0.56]; p=0.01) in HYP compared to ISO, indicating greater autophagic activation during HYP. Despite this, HSP70 protein was lower under HYP conditions following heating than ISO (0.72 [SD 0.24] vs. 1.20 [SD 0.19]; p=0.04). Contrary to our hypothesis, these preliminary findings indicate greater reliance on the autophagic response rather than simultaneous activation of HSP70 during acute heat exposure with super‐imposed hyperosmotic stress. Support or Funding Information National Science and Engineering Research Council of Canada
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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".