Human erythrocytes as early targets of thallium toxicity

VERSTRAETEN SV; DUARTE EM

Cordoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.

Thallium (Tl) is a toxicheavy metal that promotes apoptosis in cultured cells, without causing necrosis.Since the highest concentrations of Tl in intoxicated patients were found inblood, where erythrocytes (RBC) constitute the most abundant cell population,we hypothesize that these cells may be early targets of Tl toxicity. In thisstudy we investigated the effects of Tl(I) or Tl(III) exposure (5-180 min) on RBCmorphology, integrity, membrane fluidity, and the activation state of cellsignals involved in the promotion of eryptosis (RBC apoptosis). No alterationsin RBC morphology were observed. Tl(III) promoted RBC osmotic fragility and hemoglobinrelease, reaching a maximum after 120 min of incubation. In intact cells, Tl(III)decreased the fluidity of the exofacial side and hydrophobic core of RBCmembrane, without affecting the fluidity of the cytoplasmic side of themembrane. In addition, Tl(III) promoted the activation of calcium-dependentcytosolic PLA2 (cPLA2), an effect that reached a maximum after 15 min ofincubation, and that returned to baseline values at prolonged times. Together,obtained results suggest that Tl(III) ?but not Tl(I)? interact with the outerside of RBC membrane, altering their biophysical properties and promoting theactivation of signals that lead to hemolysis and/or to the promotion oferyptosis. Supported by a grant of UBA (20020130100195BA).