Mitochondrial oxygen consumption inhibition importance for TMT-dependent cell death in undifferentiated PC12 cells.

Abstract:

:The evolving role of mitochondria as a target for different death-inducing noxae prompted us to investigate trimethyltin (TMT)-dependent effects on mitochondrial functionality. For this purpose, we used a homogeneous cell culture model represented by undifferentiated PC12 cells. Mitochondria isolated from PC12 cells treated with TMT for 6, 12 and 24h, showed a time-dependent inhibition of ADP-stimulated oxygen consumption using succinate or glutamate/malate as substrate. Using a fluorescent assay, the effect of TMT on mitochondrial membrane potential (delta Psi) in PC12 cells was also determined. After 24h in culture, a strong loss of mitochondrial membrane potential (delta Psi) was observed in TMT-treated cells. Collapse of mitochondrial membrane potential correlated with an increased expression of bax/bcl-2 ratio, as evaluated by polymerase chain reaction. Western blotting and spectrophotometric analysis showed that cytochrome c release and activation of caspase 3 were concurrently induced. Our findings suggest that inhibition of mitochondrial respiration represents the early toxic event for cell death in PC12 due to trimethyltin.

journal_name

Neurochem Int

authors

Misiti F,Orsini F,Clementi ME,Lattanzi W,Giardina B,Michetti F

doi

10.1016/j.neuint.2007.11.008

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

1092-9

issue

6

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(07)00314-2

journal_volume

52

pub_type

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