Resveratrol Alleviates the Inhibitory Effect of Tunicamycin-Induced Endoplasmic Reticulum Stress on Expression of Genes Involved in Thyroid Hormone Synthesis in FRTL-5 Thyrocytes

Abstract

Recently, ER stress induced by tunicamycin (TM) was reported to inhibit the expression of key genes involved in thyroid hormone synthesis, such as sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and their regulators such as thyrotropin receptor (TSHR), thyroid transcription factor-1 (TTF-1), thyroid transcription factor-2 (TTF-2) and paired box gene 8 (PAX-8), in FRTL-5 thyrocytes. The present study tested the hypothesis that resveratrol (RSV) alleviates this effect of TM in FRTL-5 cells. While treatment of FRTL-5 cells with TM alone (0.1 µg/mL) for 48 h strongly induced the ER stress-sensitive genes heat shock protein family A member 5 (HSPA5) and DNA damage inducible transcript 3 (DDIT3) and repressed NIS, TPO, TG, TSHR, TTF-1, TTF-2 and PAX-8, combined treatment with TM (0.1 µg/mL) and RSV (10 µM) for 48 h attenuated this effect of TM. In conclusion, RSV alleviates TM-induced ER stress and attenuates the strong impairment of expression of genes involved in thyroid hormone synthesis and their regulators in FRTL-5 thyrocytes exposed to TM-induced ER stress. Thus, RSV may be useful for the treatment of specific thyroid disorders, provided that strategies with improved oral bioavailability of RSV are applied.

Thyroid Hormone Changes in the Northern Area of Tianjin during the COVID-19 Pandemic

“…Cellular stress [ 22 ] was abolished by treatment of antithyroid drug. Resveratrol (RSV) alleviates tunicamycin (TM)-induced ER stress by attenuating expression of genes involved in thyroid hormone synthesis in FRTL-5 thyrocytes [ 23 ]. Yuan Lili found that the HAMA scores in the thyrotoxic group were significantly higher than those in the subclinical thyrotoxic group and subclinical hypothyroidism group ( p =0.042; p =0.025); HAMA scores were significantly positively related to T3 and T4 ( r = 0.158, p =0.040; r = 0.169, p =0.028) [ 24 ].…”

Association of longitudinal changes in serum lipids with the natural history of subclinical hypothyroidism: A retrospective cohort study using data from the REACTION study

“…TTF-1 is critically involved in the transcriptional regulation of the expression of key thyroid hormone synthesis-related molecules. 28 Due to the relatively small sample size, the relationship between changes in TG levels and the progression to OH did not reach statistical significance, but there was still a correlation trend between them. Therefore, we cannot absolutely conclude that the changes in TG levels were completely unrelated to the progression to OH.…”

“…TTF-1 is critically involved in the transcriptional regulation of the expression of key thyroid hormone synthesis-related molecules. 28 …”

The Association Between Serum Palmitic Acid and Thyroid Function

“…( 23 ) demonstrated that PA could suppress NIS, TPO, and Tg mRNA levels, as well as promote intracellular lipid accumulation. Several studies have illustrated that endoplasmic reticulum (ER) stress could inhibit the expression of the three key molecules and their regulators in the thyrocytes ( 41 , 42 ). In addition, ER stress was also observed in HFD rats and PA-treated thyrocytes, along with the increased degradation rate of Tg, which further indicated that the effect of ER stress on HFD-induced hypothyroidism might contribute to a decrease in the production of Tg ( 35 ).…”