Tl(I) and Tl(III) induce alterations in MDCK cell lipid metabolism

MOREL GOMEZ E; VERSTRAETEN SV; FERNANDEZ MC

Chicago

Congreso; Experimental Biology 2017; 2017

Federation of American Societies for Experimental Biology

Thallium(Tl) is a toxic heavy metal that contaminates the environment and causes severalhuman health-related problems. Tl can be found as monovalent (Tl(I)) or trivalent(Tl(III)) cations, the latter being a strong oxidant. Tl intoxication alters tissularfunctioning by altering the progression of cell cycle and/or by promoting programmedcell death. Tl intoxication affects several organs and tissues, being thekidney a main target of its toxicity. The mechanisms involved in such pathologicalconditions are still poorly understood. It has been reported that other heavymetals can disturb cell lipid homeostasis. Thus, in the present work weinvestigated the effects of Tl on renal lipid metabolism, which could bepartially responsible for the toxic effects of this metal. For thispurpose, we used as a model the Madin Darby Canine Kidney (MDCK) renal epithelialcells, either in their proliferative or differentiated states. For theexperiments using proliferative MDCK cells, confluent cell cultures were incubatedfor either 24 or 48 h in the absence or presence of Tl(I) or Tl(III) (10 or 100μM). For theexperiments using differentiated cells, confluent cultures were differentiatedin hypertonic medium (NaCl, 125 mOsm) for 72 h and further were incubated for48 h in the absence or presence of Tl(I) or Tl(III) (10 or 100 μM). After treatment, cells werecollected, counted, and lipids were extracted by the Bligh-Dyer method.Chloroformic extracts were resolved by thin layer chromatography (TLC) indifferent solvent systems to evaluate the profile of phospholipids (PLs),cholesterol (Cho), and triacylglycerides (TAG). ProliferativeMDCK cells. Obtained results indicate that Tl(III) not only causes TAGaccumulation, but also increases the content of lipid membrane components (PLand Cho) and alters membrane properties. Supporting that, Tl(III) inducedalterations in the overall morphology of the cells and of the inner membranousstructures, such as mitochondria and the endoplasmatic reticulum. In addition,we observed that the alteration of lipid profile in this experimental model wasmostly caused by the enhancement of lipid biosynthesis.DifferentiatedMDCK cells. In this experimental model, both Tl(I) and Tl(III) increasedsignificantly the content of PL, Cho and TAG. Accordingly, microscopy imagesshowed morphological alterations in cells and increased the size and number oflipid droplets (LD). Also, Tl(I) and Tl(III) increased the endogenousbiosynthesis of lipids.Takentogether, obtained results using the proliferative and differentiated states ofMDCK cells indicate that Tl-mediated damage would involve severe alterations inlipid metabolism. Considering that Tl causes several human health-relatedproblems, the findings presented in this work will contribute to a clearerunderstanding of the mechanisms underlying such pathological conditions.Support orFunding Information UBACyT código 20020130100195BA PRESTAMO BID-PICT 2013-1132