Parkinson-susceptibility gene DJ-1/PARK7 protects the murine heart from oxidative damage in vivo
Bibliographic record
Abstract
Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the ability of an organism to eliminate these toxic intermediates. Although the Parkinson-susceptibility gene, Parkinson protein 7/DJ-1 (DJ-1), has been linked to the regulation of oxidative stress, the exact mechanism by which this occurs and its in vivo relevance have remained elusive. In the heart, oxidative stress is a major contributor to the development of heart failure (HF). Therefore, we hypothesized that DJ-1 inhibits the pathological consequences of ROS production in the heart, the organ with the highest oxidative burden. We report that DJ-1 is highly expressed in normal heart tissue but is markedly reduced in end-stage human HF. DJ-1-deficient mice subjected to oxidative stress by transaortic banding exhibited exaggerated cardiac hypertrophy and susceptibility to developing HF. This was accompanied by a Trp53 (p53)-dependent decrease in capillary density, an excessive oxidation of DNA, and increased cardiomyocyte apoptosis, key events in the development of HF. Impaired mitochondrial biogenesis and progressive respiratory chain deficiency were also evident in cardiomyocytes lacking DJ-1. Our results provide compelling in vivo evidence that DJ-1 is a unique and nonredundant antioxidant that functions independent of other antioxidative pathways in the cellular defense against ROS.
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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 | 0.001 | 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".