Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK
Bibliographic record
Abstract
We have earlier shown that the treatment of A10 vascular smooth muscle cells with S-nitroso-N-acetyl-penicillamine (SNAP); nitric oxide donor (NO) for 24 h decreased the expression of natriuretic peptide receptor C (NPR-C) and adenylyl cyclase signaling. The present study was undertaken to examine the implication of different signaling mechanisms in a NO-induced response. The treatment of A10 vascular smooth muscle cells with SNAP decreased the expression of NPR-C and G(i)alpha proteins in a time-dependent manner. The expression of G(i)alpha proteins was decreased at 6 h, whereas the expression of NPR-C was attenuated at 2 h. The NPR-C-mediated inhibition of adenylyl cyclase was attenuated (approximately 50%) after 2 h of treatment and was completely abolished after 6 h of treatment. The decreased expression of NPR-C and NPR-C-mediated attenuation of adenylyl cyclase after 2 h of treatment was reversed to control levels by PD-98059, a MEK inhibitor. SNAP also modulated the ERK1/2 phosphorylation in a time-dependent manner; an increase was observed up to 2 h, and, thereafter, the ERK1/2 phosphorylation was decreased. On the other hand, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823 inhibitor of soluble guanylyl cyclase and protein kinase G, respectively, and Mn(III)tetrakis(4-benzoic acid)porphyrin, a scavenger of peroxynitrite, were unable to restore the SNAP-induced decreased expression of NPR-C protein and increased ERK1/2 phosphorylation to control levels. However, the decreased levels of phosphorylated ERK1/2 and G(i)alpha proteins were restored to control levels by 8-bromo-cAMP. These results indicate that a temporal relationship follows between a NO-induced decreased expression of NPR-C and G(i)alpha proteins. The decreased expression of NPR-C is mediated through cGMP-independent but MAPK-dependent pathway, whereas NO-induced decreased levels of cAMP may contribute to the decreased activation of MAPK and thereby decreased the expression of G(i)alpha proteins.
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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) | 0.001 | 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".