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

Wanda Lattanzi, Francesco Misiti, Federica Orsini, Bruno Giardina, Fabrizio Michetti, M. Elisabetta Clementi

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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 24 h, 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 (ΔΨ) in PC12 cells was also determined. After 24 h in culture, a strong loss of mitochondrial membrane potential (ΔΨ) 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.
Original languageEnglish
Pages (from-to)1092-1099
Number of pages8
JournalNeurochemistry International
Publication statusPublished - 2008

Keywords

  • Mitochondria
  • Mitochondrial membrane potential
  • Pheochromocytoma 12
  • Trimethyltin

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