Is the metabolism of extracellular ATP involved in thallium-mediated cytotoxicity?

VERSTRAETEN SV; SALVATIERRA FRÉCHOU DM; SCHWARZBAUM PJ

Cordoba

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

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.

We demonstrated previously that Tl(III) -butno Tl(I)- promotes rapid release of ATP (eATP) from adherent PC12 cells viapannexin channels and exocytosis. Tl(III) also inhibits irreversibly theactivity of ectoATPases that act in the micromolar range of eATP concentration.In this work we investigated the effects of Tl on cell viability and ifthose effects could be related to altered eATP metabolism. Cell incubation inthe presence of 100 µM Tl(I) or Tl(III) for 1-72 h caused time-dependentdecrease of cell viability evaluated from MTT reduction. This effect was accompanied by decreased amounts ofadhered cells, with no viable cells detected in the culture media. Todiscriminate the causes of Tl-mediated cell death, samples wereanalyzed by flow cytometry to evaluate the content of hypodiploid cells, andthe supernatants were tested for lactate dehydrogenase activity to assessnecrosis. While necrosis was negligible, the amount of hypodiploid cells wassignificantly increased after 72 h of Tl(III) exposure. To investigate if alterations ineATP metabolism may be involved in the early steps of cell response to Tl(III),eATP was removed by adding apyrase to the culture media. The removal of eATPenhanced the noxious effect of Tl on cell viability, suggesting that eATP may playa protective role in Tl-mediated cell death. Supported by UBA (20020130100195BA) and ANPCyT(PICT2013-1018).