GW24-e3625 Effects of apelin on the phosphodiesterase 1 expression and oxidative stress levels in mouse kidney fibroblast cells
Bibliographic record
Abstract
Objectives Apelin is a recently-discovered cardiovascular bioactive polypeptide with multiple biological effects, which is the endogenous ligand of the orphan G protein-coupled receptor-APJ receptor and may cause vasodilation and lower blood pressure levels. This study focused on the effects of Apelin on the phosphodiesterase 1 (PDE1) expression and oxidative stress levels in mouse kidney fibroblast cells. Methods The mouse kidney fibroblast cells were primary cultured using the routine method. The angiotensin II (Ang II; 100 nmol/L) was used to stimulate the cells for 1 h in the presence and absence of Aplein (100 nmol/L), PDE1 inhibitor vinpocetine (10 μmol/L) and extracellular regulated protein kinase (ERK) inhibitor PD98059 (10 mmol/L). The specific fluorescent probe-dihydropyridinum (DHE) staining and colorimetric method were used for the determination of superoxide generation and malondialdehyde (MDA) content in cells, respectively. Results In the cultured mouse kidney fibroblast cells, exposure to Ang II (100 nmol/L) obviously promoted protein expressions of PDE1A and PDE1B (n = 5-6; P < 0.01, respectively), without having a differential effect on the expression of PDE1C. These changes were associated with marked increases in phosphorylated expression of ERK1/2, superoxide generation and MDA levels (n = 5-6; P < 0.01, respectively). In addition, treatment with Apelin (100 nmol/L) and PDE1 inhibition with vinpocetine (10 μmol/L) significantly prevented expressions of PDE1A and PDE1B mediated by Ang II in cells (n = 5; P < 0.05, respectively). More importantly, intervention with Apelin (100 nmol/L) and vinpocetine (10 μmol/L) strikingly reduced the cellular oxidative stress in response to Ang II, as evidenced by decreases in MDA levels and superoxide production, linked with a marked downregulation in phosphorylated ERK1/2 levels (n = 5-6; P < 0.05 or P < 0.01, respectively). Conclusions Treatment withApelin significantly prevents the oxidative stress formation in cultured mouse kidney fibroblast cells in response to Ang II through the modulation of PDE1-ERK1/2 signalling pathway, suggesting the potential anti-oxidative stress effect of Apelin. The enhanced activities and/or expression of Apelin may have potential therapeutic benefits on renal diseases associated with oxidative stress. This work was supported by National Natural Science Foundation of China (81170246 & 30973522) and Shanghai Pujiang Talents Program (11PJ1408300).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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 teacher head, 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".