EGF prevents thallium-induced PC12 cells apoptosis by modulating the activation of p53, JNK and p38

PINO, M. T. L.; VERSTRAETEN, S.V

Mendoza

Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2012

In PC12 cells with or without added EGF, thallium (Tl) increases cyclins D1 and E contents, and arrests cells cycle in G0/G1. EGF also protects cells from Tl-mediated apoptosis. In this study we analyzed the expression of p21 and p53, involved in cell cycle arrest. Tl(I) and Tl(III) increased nuclear p53 content which was prevented by EGF. Tl(I) and Tl(III) increased cytosolic p21 content regardless EGF presence. Even when the activation of Ras/Raf/MEK/ERK pathway by EGF is an early event, p-ERK was still increased after 24 h of Tl treatment. Tl(I) increased the pro-apoptotic MAPK p-p38, which was partially prevented by EGF. Tl(III) increased p-p38 but only at 100 mM concentration. c-jun phosphorylation by JNK1 participates in G1 to S phase transition, while its phosphorylation by JNK2 targets c-jun for degradation. Tl(I) increased p-JNK1, which was prevented by EGF. Tl(III) did not affect JNK1 phosphorylation, and low levels of p-JNK1 were detected in EGF-supplemented cells. Tl(I), but not Tl(III), increased p-JNK2, which was prevented by EGF. Finally, EGF decreased the content of c-jun in Tl(I)- and Tl(III)-treated cells nuclei. Together, results indicate that the protective effect of EGF on Tl-mediated cell apoptosis may proceed by the prevention of the activation of pro-apoptotic MAPKs. Work supported by grants of the University of Buenos Aires and CONICET, Argentina.