Acute Maneb Exposure Significantly Alters Both Glycolysis and Mitochondrial Function in Neuroblastoma Cells

Toxicological Sciences : an Official Journal of the Society of Toxicology
Colin C AndersonJames R Roede

Abstract

The pesticides paraquat (PQ) and maneb (MB) have been described as environmental risk factors for Parkinson's disease (PD), with mechanisms associated with mitochondrial dysfunction and reactive oxygen species generation. A combined exposure of PQ and MB in murine models and neuroblastoma cells has been utilized to further advance understanding of the PD phenotype. MB acts as a redox modulator through alkylation of protein thiols and has been previously characterized to inhibit complex III of the electron transport chain and uncouple the mitochondrial proton gradient. The purpose of this study was to analyze ATP-linked respiration and glycolysis in human neuroblastoma cells utilizing the Seahorse extracellular flux platform. Employing an acute, subtoxic exposure of MB, this investigation revealed a MB-mediated decrease in mitochondrial oxygen consumption at baseline and maximal respiration, with inhibition of ATP synthesis and coupling efficiency. Additionally, MB-treated cells showed an increase in nonmitochondrial respiration and proton leak. Further investigation into mitochondrial fuel flex revealed an elimination of fuel flexibility across all 3 major substrates, with a decrease in pyruvate capacity as well as glutamine de...Continue Reading

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Citations

Aug 24, 2019·International Journal of Molecular Sciences·Dakota B WardMonica A Valentovic
Apr 10, 2020·Environmental Science and Pollution Research International·Raquel VieiraLuís M Félix
Aug 28, 2020·International Journal of Molecular Sciences·Lars KaiserHans-Peter Deigner
Apr 15, 2020·Pesticide Biochemistry and Physiology·Samreen SalamRiaz Mahmood
Jan 12, 2021·Frontiers in Cellular Neuroscience·Shuheng WenKoichi Uemura
Dec 7, 2020·Free Radical Biology & Medicine·Colin C AndersonJames R Roede
May 6, 2020·Toxicology Reports·Colin C AndersonJames R Roede
Jun 16, 2021·Free Radical Biology & Medicine·Colin C AndersonJames R Roede

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