Tl(I) and Tl(III) induce reticulum stress in MDCK cells

MOREL GOMEZ, EMANUEL; CASALI, CECILIA IRENE; FERNANDEZ , MARIA DEL CARMEN; VERSTRAETEN, SANDRA

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2023

1382-6689

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 LC3b 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 b-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.