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

Neurochemistry International
Francesco MisitiFabrizio Michetti

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.

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Citations

Oct 16, 2015·Neurotoxicology·Cinzia FabriziLorenzo Fumagalli
Mar 19, 2011·Neurochemistry International·Maria Concetta GelosoFabrizio Michetti
Jul 6, 2015·European Journal of Pharmacology·Yoon Jeong NamChung Soo Lee
May 10, 2015·Neurotoxicity Research·Jintao YuJerome A Roth
Feb 25, 2014·International Journal of Cell Biology·Cinzia FabriziLorenzo Fumagalli
May 27, 2020·Journal of Neural Transmission·Elena PompiliFrancesco Fornai
Oct 17, 2017·Acta Parasitologica·Mohamed Abdo RizkSabry El-Khodery
Dec 29, 2019·International Journal of Molecular Sciences·Sabrina CeccarigliaCarlo Gangitano
Aug 8, 2021·International Journal of Molecular Sciences·Soon-Ae KimEun-Hye Jang

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