Roles of endoplasmic reticulum stress in 2,2?,4,4?-tetrabromodiphenylether-induced thyroid cell apoptosis and autophagy

Polybrominated diphenyl ethers are known to be toxic and impair thyroid function. However, the underlying molecular mechanisms are not well understood. We constructed a female Sprague-Dawley rat model to evaluate the role of endoplasmic reticulum stress, apoptosis and autophagy in 2,2?,4,4?-tetrabromodiphenylether (PBDE47) induced thyroid toxicity. In the brain development spurt period (postnatal day 10), rats were treated with PBDE-47 (0, 1, 5, 10 mg/kg bw, i.g). Two addition groups were administered with 4-Phenylbutyric acid, an endoplasmic reticulum stress modulator, to reverse PBDE-47-induced thyroid toxicity. Our results demonstrated that PBDE-47 significantly decreased serum thyroid stimulating hormone levels, induced histologic changes in thyroid tissues, increased the percentage of cell apoptosis and expression levels of C/EBP-homologous protein, caspase 3, glucose-regulated protein 78, inositol-requiring enzyme 1, and autophagy-related proteins Beclin1 and 1A/1B-light chain 3. Besides of decreased serum thyroid stimulating hormone levels, all these changes were reversed by 4-Phenylbutyric acid. Taken together, these data indicate that, PBDE-47 damages the thyroid tissues by triggering endoplasmic reticulum stress, apoptosis and autophagy.

Automated summary

Research indicates that PBDE-47 damages thyroid tissues by triggering endoplasmic reticulum stress, apoptosis, and autophagy, and these changes can be reversed by 4-Phenylbutyric acid.