Apoptosis of NOD.H2 <sup>h4</sup> Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress
Bibliographic record
Abstract
BACKGROUND: Enhanced iodide intake in NOD.H2(h4) mice accelerates the incidence and severity of spontaneous autoimmune thyroiditis (SAT) via an unknown mechanism. A plausible hypothesis is that iodide-induced apoptosis of thyrocytes can create imbalances in antigenic load and/or disruption of immunoregulatory mechanisms that facilitate activation of autoreactive T cells in cervical lymph nodes draining the thyroid. METHODS: We examined whether NOD.H2(h4) thyrocytes, exposed to low NaI concentrations in vitro, are more susceptible to apoptosis compared to thyrocytes from CBA/J mice, which are resistant to iodide-accelerated SAT (ISAT). We also looked, at the transcriptional level, for differential activation of genes involved in apoptosis or oxidative stress pathways that may account for potential differences in iodide-mediated apoptosis between NOD.H2(h4) and CBA/J thyrocytes. RESULTS: We report that NOD.H2(h4) thyrocytes, cultured for 24 h at very low (4-8 μM) concentrations of NaI, exhibit high levels (40-55%) of apoptosis, as assessed microscopically following staining with fluorescent caspase inhibitors. Similar treatment of thyrocytes from CBA/J mice, which are resistant to ISAT, yielded significantly lower (10-20%) apoptotic rates. Expression analysis by real-time polymerase chain reaction using arrays of apoptosis- and oxidative stress-related genes showed that NaI intake upregulates the expression of 22 genes involved in ROS metabolism and/or antioxidant function in CBA/J thyrocytes, whereas only two of these genes were upregulated in NOD.H2(h4) thyrocytes. Among the set of overexpressed genes were those encoding thyroid peroxidase (Tpo; 5.77-fold), glutathione peroxidases (Gpx2, Gpx4, Gpx7; 2.03-3.14-fold), peroxiredoxins (Prdx1, Prdx2, Prdx5; 2.27-2.97-fold), superoxide dismutase 1 (Sod1; 3.57-fold), thioredoxin 1 (Txn1; 2.13-fold), and the uncoupling proteins 2 and 3 (Ucp2, Ucp3; 2.01-2.15-fold). CONCLUSIONS: The results demonstrate that an impaired control of oxidative stress mechanisms is associated with the observed high susceptibility of NOD.H2(h4) thyrocytes to NaI-mediated apoptosis, and suggest a contributing factor for the development of ISAT in this strain.
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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 | 0.001 |
| 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".