Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Ciencias Biológicas, Cátedra de Biología Celular y Molecular, Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Ciencias Biológicas, Cátedra de Biología Celular y Molecular, Buenos Aires, Argentina; Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini (IQUIFIB)-Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Environ Toxicol Pharmacol. 2023 Aug;101:104192. doi: 10.1016/j.etap.2023.104192. Epub 2023 Jun 20.
The effects of the exposure of proliferating MDCK cells to thallium [Tl(I) or Tl(III)] on cell viability and proliferation were investigated. Although Tl stopped cell proliferation, the viability was > 95%. After 3 h, two autophagy markers (SQSTM-1 expression and LC3β localization) were altered, and at 48 h increased expression of SQSTM-1 (60%) and beclin-1 (50-100%) were found. At 24 h, the expression of endoplasmic reticulum (ER) stress markers ATF-6 and IRE-1 were increased in 100% and 150%, respectively, accompanied by XBP-1 splicing and nuclear translocation. At 48 h, major ultrastructure abnormalities were found, including ER enlargement and cytoplasmic vacuolation which was not prevented by protein synthesis inhibition. Increased PHB (85% and 40% for Tl(I) and Tl(III), respectively) and decreased β-tubulin (45%) expression were found which may be related to the promotion of paraptosis. In summary, Tl(I) and Tl(III) promoted ER stress and probably paraptosis in MDCK cells, impairing their proliferation.
研究了增殖的 MDCK 细胞暴露于铊（Tl（I）或 Tl（III））对细胞活力和增殖的影响。尽管 Tl 停止了细胞增殖，但细胞活力>95%。3 小时后，两种自噬标记物（SQSTM-1 表达和 LC3β定位）发生改变，48 小时时发现 SQSTM-1（60%）和 beclin-1（50-100%）表达增加。24 小时时，内质网（ER）应激标志物 ATF-6 和 IRE-1 的表达分别增加了 100%和 150%，同时伴随着 XBP-1 剪接和核转位。48 小时时，发现了主要的超微结构异常，包括 ER 扩大和细胞质空泡化，而蛋白质合成抑制并不能预防这种情况。发现 PHB（Tl（I）和 Tl（III）分别增加了 85%和 40%）和 β-微管蛋白（减少了 45%）表达降低，这可能与促进 Paraptosis 有关。综上所述，Tl（I）和 Tl（III）促进了 MDCK 细胞的 ER 应激，可能还促进了 Paraptosis，从而损害了它们的增殖。
