Tl(I) and Tl(III) differentially affect the metabolism of extracellular ATP in PC12 cells

SALVATIERRA FRÉCHOU DM; ALVAREZ CL; SCHWARZBAUM PJ; VERSTRAETEN SV

Rosario

Congreso; L Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

We previously demonstrated that Tl(I) and Tl(III) (100 mM) induced PC12 cell apoptosis. In this study, we investigated the hypothesis that a misbalanced homeostasis of extracellular ATP (eATP) may participate in the initial steps of Tl-mediated apoptosis. Homeostasis of eATP depends on the balance between the rates of ATP release and extracellular ATP hydrolysis (i.e. ectoATPase activity). Signaling of eATP is effected through activation of purinergic receptors. Release of ATP was negligible with Tl(I) and amounted to 10.6±2.2 pmol ATP/min/106 cells with Tl(III). This release was inhibited 70% by carbenoxolone (pannexin 1 inhibitor) and 50% by brefeldin A (exocytosis inhibitor). EctoATPase activity was increased 65% by Tl(I) and reduced 68% by Tl(III). Together, results suggest that even when Tl(I) does not promote per se the release of ATP, it accelerates eATP hydrolysis which would limit the duration of eATP-mediated cell signaling. In contrast, Tl(III) promotes ATP release and inhibits eATP hydrolysis by ectoATPases, which would increase the duration of eATP cell signaling. Supported by grants of UBA (20020100100112) and CONICET (PIP112-201101-00639).