Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
Horm Metab Res. 2011 May;43(5):331-6. doi: 10.1055/s-0030-1269907. Epub 2011 Jan 10.
In thyroid cells, the effects of all- TRANS retinoic acid (ATRA) on sodium/iodide symporter (NIS) and CCAAT/enhancer-binding protein-homologous protein (CHOP) under condition of endoplasmic reticulum (ER) stress have not been evaluated. In the present study, the relationships between NIS, CHOP, and p38 MAPK, and the effects of ATRA on NIS and CHOP expression as well as on p38 MAPK activation under condition of ER stress in thyroid cells were investigated. In FRTL5 thyroid cells, NIS mRNA and protein levels decreased following tunicamycin (TN) treatment, while CHOP mRNA and protein levels increased. In addition, while CHOP mRNA levels decreased after administration of tauro-UDCA and siCHOP, NIS mRNA levels were not altered. After pretreatment with SB203580, NIS mRNA levels decreased in non-TN-treated cells but increased in TN-treated cells. In contrast, CHOP mRNA levels decreased in both non-TN-treated and TN-treated cells. Exposure to ATRA decreased NIS mRNA levels in non-TN-treated cells but increased NIS mRNA levels in TN-treated cells. ATRA decreased CHOP mRNA levels in both non-TN-treated and TN-treated cells although the response was significant only in TN-treated cells. Phospho-p38 MAPK protein levels but not total p38 MAPK protein levels increased in TN-treated cells. ATRA attenuated this increase in phopho-p38 MAPK protein levels. In conclusion, our results demonstrate that ER stress may induce reciprocal changes in NIS and CHOP expression via p38 MAPK in FRTL5 thyroid cells, and that ATRA may attenuate ER stress-induced alterations in NIS and CHOP expression by modulating the phosphorylation of p38 MAPK in FRTL5 thyroid cells.
在甲状腺细胞中，全反式视黄酸（ATRA）在内质网（ER）应激条件下对钠/碘同向转运体（NIS）和 CCAAT/增强子结合蛋白同源蛋白（CHOP）的影响尚未得到评估。本研究旨在探讨 NIS、CHOP 与 p38MAPK 的关系，以及 ATRA 在甲状腺细胞 ER 应激条件下对 NIS 和 CHOP 表达以及 p38MAPK 激活的影响。在 FRTL5 甲状腺细胞中，经衣霉素（TN）处理后 NIS mRNA 和蛋白水平降低，而 CHOP mRNA 和蛋白水平升高。此外，牛磺熊去氧胆酸（tauro-UDCA）和 siCHOP 给药后 CHOP mRNA 水平降低，但 NIS mRNA 水平不变。SB203580 预处理后，非 TN 处理细胞中 NIS mRNA 水平降低，但 TN 处理细胞中 NIS mRNA 水平升高。相反，CHOP mRNA 水平在非 TN 处理和 TN 处理细胞中均降低。ATRA 降低非 TN 处理细胞中 NIS mRNA 水平，但增加 TN 处理细胞中 NIS mRNA 水平。ATRA 降低非 TN 处理和 TN 处理细胞中 CHOP mRNA 水平，但仅在 TN 处理细胞中反应显著。TN 处理细胞中磷酸化 p38MAPK 蛋白水平而非总 p38MAPK 蛋白水平升高。ATRA 减弱了磷酸化 p38MAPK 蛋白水平的这种增加。综上所述，本研究结果表明，在 FRTL5 甲状腺细胞中，内质网应激可能通过 p38MAPK 诱导 NIS 和 CHOP 表达的相互变化，而 ATRA 可能通过调节 FRTL5 甲状腺细胞中 p38MAPK 的磷酸化来减轻内质网应激诱导的 NIS 和 CHOP 表达改变。
