Differential regulation of thioredoxin and NAD(P)H oxidase by angiotensin II in male and female mice
Bibliographic record
Abstract
OBJECTIVE: We hypothesized that downregulation of the antioxidant thioredoxin system contributes to oxidative stress in angiotensin II-induced hypertension. As oestrogen may protect against oxidative stress, we also evaluated whether the thioredoxin system, particularly in the heart, is differentially regulated between females and males. RESULTS: C57Bl/6 male and intact or ovariectomized female mice were infused with angiotensin II (400 ng/kg per minute for 2 weeks). Systolic blood pressure (SBP) was increased by angiotensin II in both groups week 1 and increased further in males versus females in week 2. Angiotensin II increased SBP from 112 +/- 6 to 143 +/- 9 mmHg in ovariectomized mice. Basal cardiac thioredoxin expression and reductase activity were significantly higher (two to threefold) in females versus males. Angiotensin II increased thioredoxin expression (approximately threefold), thioredoxin reductase activity, nicotinamide adenine dinucleotide phosphate, reduced form (NAD(P)H) oxidase activity and plasma thiobarbituric acid-reducing substances in males but not in females. Angiotensin II increased thioredoxin expression and NAD(P)H oxidase activity in ovariectomized versus control mice. Apurinic/apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) activation, which interacts with thioredoxin to activate inflammatory transcription factors, was increased by angiotensin II only in males. CONCLUSION: These results demonstrate sex dimorphism with respect to thioredoxin, oxidative stress and inflammation, and suggest the differential regulation of blood pressure, the cardiac thioredoxin system and NAD(P)H oxidase activity by angiotensin II in male and female mice. Whereas angiotensin II increases the activity of thioredoxin reductase and APE/Ref-1, enhances oxidative stress, and amplifies blood pressure elevation in males, it has little effect in females. Such differences may partly relate to the protective actions of oestrogens.
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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 | 0.000 |
| 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) | 0.000 | 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".