Nitration of aldolase: a critical post-translational modification in nitric oxide-mediated regulation of mast cell function (80.6)
Bibliographic record
Abstract
Abstract Nitric oxide (NO) is a short-lived free radical that regulates mast cell (MC) activities including inhibition of MC degranulation. To elucidate the molecular mechanisms underlying the effects of NO in MC, we investigated protein tyrosine nitration in human mast cell lines treated with the NO donor S-Nitrosoglutathione. Using 2D gel western blot analysis with an anti-nitrotyrosine antibody together with mass spectroscopy, we identified aldolase A, an enzyme of the glycolytic pathway as a target for tyrosine nitration in MC. Aldolase A nitration was associated with reduction in the Km and Vmax of aldolase in HMC-1 and LAD-2. Nuclear Magnetic Resonance analysis showed that despite these changes in activity of a critical enzyme in glycolysis, there was no significant change in total cellular ATP content, although the AMP/ATP ratio was increased. Elevated levels of lactate and pyruvate suggested that NO treatment enhanced glycolysis in MC. Reduced MC aldolase activity was associated with increased intracellular levels of its substrate, fructose 1,6 bisphosphate (FBP). Interestingly, FBP inhibited IgE-mediated MC degranulation in LAD-2 cells. Thus for the first time we report evidence of protein tyrosine nitration in two human MC lines and identify aldolase A as a prominent target that may regulate MC phenotype and function. Funded by: Canadian Institutes of Health Research, The Lung Association, Alberta & NWT and 75th Anniversary Award, University of Alberta.
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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".