Abstract 647: Histone Deacetylase 1 Reduces No Production In Endothelial Cells Via Lysine Deacetylation Of No Synthase 3
Bibliographic record
Abstract
The lysine acetylation state of non-histone proteins may be regulated through histone deacetylases (HDACs). Evidence suggests that NO synthase 3 (NOS3; eNOS) is post-translationally lysine acetylated leading to increased NO production in the endothelium. The purpose of this study was to test the hypothesis that NOS3 is lysine-acetylated and that upregulated HDAC1-mediated deacetylation leads to reduced NO production in endothelial cells. We determined that NOS3 is basally lysine acetylated in cultured bovine aortic endothelial cells (BAECs). In BAECs, HDAC1 is expressed in the nucleus and cytosol, and forms a novel protein-protein interaction with NOS3. Overexpression of HDAC1 in BAECs resulted in a significant reduction in NOS3 lysine acetylation (control = 1.0 ± 0.1, HDAC1 = 0.59 ± 0.08 A.U., P < 0.01), while HDAC1 knockdown with siRNA resulted in no significant change in NOS3 acetylation level. Moreover, overexpression or knockdown of HDAC1 resulted in no significant effect on NOS3 protein expression or on expression levels of NOS3 phosphorylation sites T497, S635, S1179. HDAC1 overexpression in BAECs significantly blunted basal nitrite production (an index of nitric oxide production; control 287.7 ± 29.1 pmol/mg p/h, HDAC1 172.4 ± 31.7 pmol/mg p/h, P < 0.05) as well as attenuating endothelin-1 stimulated nitrite production (control 481.8 ± 50.3 pmol/mg/h, HDAC1 243.1 ± 48.2 pmol/mg/h, P< 0.05). On the contrary, HDAC1 knockdown increased basal nitrite production (730.6 ± 99.1 pmol/mg/h), and further exaggerated increases in endothelin-1 stimulated nitrite production (1276.9 ± 288.2 pmol/mg/h). Thus, these data indicate that up-regulated HDAC1 decreases NOS3 activity, most likely, through direct lysine deacetylation of NOS3. We propose that HDAC1-mediated deacetylation of NOS3 may represent a novel target for endothelial dysfunction.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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) | 0.006 | 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".