IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Tl(I) and Tl(III) induce a novel type of cell death (paraptosis) in proliferating MDCK cells
Autor/es:
MOREL GÓMEZ ED; VERSTRAETEN SV; FERNANDEZ MC
Reunión:
Congreso; LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2018
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
Thallium (Tl) is a toxic heavy metal that contaminates the environment and affects human health. Tl intoxication affects several organs and tissues through still poorly understood mechanisms, the kidney being a main target of Tl toxicity. Tl has two oxidation states, the monovalent (Tl(I)) and trivalent (Tl(III)) cations. We demonstrated previously that both Tl(I) and Tl(III) alter lipid metabolism in proliferating renal epithelial (MDCK) cells, increasing the content of phospholipids, cholesterol and triglycerides, as well as the number of lipid droplets. In this work we investigated further the possible mechanisms underlying those alterations. Confluent MDCK cells were incubated for 24 or 48 h in the absence orpresence of Tl(I) or Tl(III) (10 or 100 μM). Phase-contrast and transmission electron  microscopy evidenced cytoplasmic vacuolation that could be related to non-apoptotic death. RT-PCR analysis indicated that both Tl(I) and Tl(III) increased prohibitin (positive paraptosis modulator) expression without changing phosphatidylethanolamine-binding protein (negative paraptosis modulator) expression. Expression levels of proteins involved in autophagy and ER stress were analyzed by Western blot. Tl(I) and Tl(III) increased the expression of IRE-1, ATF-6, beclin-1 and sequestrin-1. Together, obtained results indicate that morphological and lipid metabolism alterations could be mediated by autophagy, ERstress and paraptosis, the latter explaining the increased contents of phospholipid and cholesterol in Tl-exposed MDCK cells.