Thallium induces PC12 cells apoptosis through the activation of multiple molecular pathways

HANZEL, C. E.; VERSTRAETEN, S. V.

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Reunión Annual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

SAIB

Thallium (Tl) is a non-essential heavy metal, with two oxidation states (Tl and Tl ). Tl is highly neurotoxic through still poorly understood mechanisms.We previously demonstrated in PC12 cells that Tl and Tl altered cells redox state and increased the number of apoptotic nuclei (~26% at 100 M Tl or Tl ). To elucidate the molecular pathways of cells death, PC12 cells were incubated with Tl or Tl (10-100 M) for 24h. We found higher PARP cleavage (~70% at 100 MTl orTl ), cytochrome c release (~60% at 100 M Tl ), and AIF translocation (~70% at 100 M Tl ). Total Bcl-2 content remained unaffected. Accordingly to the higher PARP cleavage, a significant increase in caspase 3 activity was found (100 M Tl or Tl ). Phosphatidylserine exposure was only found when PC12 cells were treated with 100 M Tl . Besides, an increase in caspase 8 activity was observed when the cells were incubated in the presence of 50 M Tl . Significant lysosomal labilization as determined by catepsin D activity in cytosol was observed in cells treated with Tl or Tl (50-100 M). Together, present results indicate that Tl or Tl induce apoptosis in PC12 cells through the activation of multiple cellular pathways, effect that depends on metal speciation and concentration. This work was supported by grants of UBA (B072) and CONICET (PIP 5536), Argentina.