Angiotensin II-evoked enhanced expression of RGS2 attenuates Gi-mediated adenylyl cyclase signaling in A10 cells
Bibliographic record
Abstract
OBJECTIVE: We have recently shown that pretreatment of A10 vascular smooth muscle cells (VSMC) with angiotensin II (Ang II) for 24 h enhanced the expression of Gialpha-proteins, however, Gialpha-mediated adenylyl cyclase signaling was attenuated. Since regulators of G-protein signaling (RGS) have been shown to negatively regulate the Galpha-protein, we investigated the role of RGS2, in Ang II-induced attenuation of Gialpha-mediated signaling in A10 vascular smooth muscle cells (VSMC). METHODS: A10 VSMC were incubated with Ang II (10(-7) M) for different periods of time at 37 degrees C. The levels of G-proteins and RGS2 protein were determined by immunoblotting using specific antibodies. Adenylyl cyclase activity stimulated or inhibited by agonists was determined to examine the functions of G-proteins. RESULTS: Ang II treatment of A10 VSMC enhanced the expression of Gialpha and RGS2 proteins in a time-dependent manner, the maximal expression of Gialpha-proteins was observed at 1 h that remained elevated up to 24 h, whereas enhanced expression of RGS2 in these cells was detected at 1 h, peaked at 2 h and returned to base line level by 8 h. The increased expression of RGS2 by Ang II was inhibited by actinomycin D. The increased expression of Gialpha at 30 min when the levels of RGS2 were not augmented was reflected in increased Gi functions as was demonstrated by increased inhibition of adenylyl cyclase by inhibitory hormones (receptor-dependent functions) and increased inhibition of forskolin (FSK)-stimulated adenylyl cyclase by GTPgammaS (receptor-independent functions). However, with increased expression of RGS2, the Gi-mediated functions started declining and were completely abolished at 2 h of treatment when the levels of RGS2 were maximally augmented. Furthermore, prior treatment of cells with RGS2 antibody, that completely attenuated Ang II-induced expression of RGS2, prevented the GTPgammaS-induced attenuation of FSK-stimulated adenylyl cyclase activity. In addition, treatment of the cells with Ang II for 30 min that increased the levels of Gialpha-protein and not of RGS2 protein resulted in the attenuation of Gsalpha-mediated isoproterenol-induced stimulation of adenylyl cyclase and this attenuation was restored to control level at 1 h and remained unchanged thereafter. CONCLUSION: These results suggest that RGS2 may be involved in short-term regulation of Ang II-induced Gi-mediated adenylyl cyclase signalling.
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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) | 0.001 | 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 | 0.001 |
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".