Effect of hydrogen peroxide and high glucose concentration on the calcium regulatory system of the human vascular endothelial cells in vitro
Bibliographic record
Abstract
Many studies have demonstrated that there is a strong relationship between endothelial dysfunction and oxidative stress and have demonstrated also that hyperglycemia is associated with increased generation of oxidative stress and atherosclerotic vascular diseases, but we do not know how hydrogen peroxide (H2O2) and high glucose (HG) could affect calcium regulatory proteins of human vascular endothelial cells (HUVECs) in vitro. In the present study, we have examined the acute effect of H2O2 (100 M) and the effect of chronic exposure to HG concentration (35 mM) on the calcium regulatory system of human vascular endothelial cells using fluorescence imaging microscopy (fura-2). In this study, we tested the hypothesis that calcium regulatory proteins (SERCA-ATPase and PMCA-ATPase pumps and the NCX exchanger) of ECs have different sensitivities to H2O2 and high glucose concentration. We also tested the hypothesis that calcium regulatory proteins could be potential targets of ROS at the early stage of vascular disease. The results of this study showed that both H2O2 and high glucose induced significant delay in calcium removal time (CRT). The study of H2O2 showed that the delay in CRT was due to partial inhibition of SERCA-ATPase and the sodium calcium exchanger (NCX) activity and the effect of H2O2 on CRT was reversible. In contrast, the PMCA-ATPase pump was resistant to inhibition by H2O2. Furthermore, H2O2 induced a 40 ± 6.5 % reduction in endoplasmic reticulum refilling. The second part of the study showed that exposure of ECs to HG concentration for 10 days induced a significant delay in CRT and this delay was due to partial blockade of the SERCA-ATPase pump. Blockade of PMCA-ATPase pump with vanadate showed a further delay in CRT. We conclude that: 1- Both H2O2 and HG affected components of the calcium removal system with different sensitivities; 2- H2O2 and HG did not show any inhibitory effects on the PMCA-ATPase pump; 3- The effect of H2O2 on CRT was reversible; 4- The effect of HG on CRT could be due to increased production of H2O2; 5- The calcium regulatory proteins of ECs could be potential targets for ROS during the early stage of a cardio-vascular disease such as diabetes mellitus.
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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 | 0.001 | 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".