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dc.contributor.authorMapa, Mapa S.T.
dc.contributor.authorLe, Viet Q.
dc.contributor.authorWimalasena, Kandatege
dc.date.accessioned2018-09-26T21:27:17Z
dc.date.available2018-09-26T21:27:17Z
dc.date.issued2018-08-23
dc.identifier.citationMapa MST, Le VQ, Wimalasena K (2018) Characteristics of the mitochondrial and cellular uptake of MPP+ , as probed by the fluorescent mimic, 4’I-MPP+ . PLoS ONE 13(8): e0197946. https://doi.org/10.1371/journal.pone.0197946en_US
dc.identifier.urihttp://dx.doi.org/10.1101/321687
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0197946
dc.identifier.urihttp://hdl.handle.net/10057/15514
dc.descriptionCopyright: © 2018 Mapa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.description.abstractThe discovery that 1-methyl-4-phenylpyridinium (MPP+ ) selectively destroys dopaminergic neurons and causes Parkinson’s disease (PD) symptoms in mammals has strengthened the environmental hypothesis of PD. The current model for the dopaminergic toxicity of MPP+ is centered on the uptake into dopaminergic neurons, accumulation into the mitochondria, inhibition of the complex-I leading to ATP depletion, increased reactive oxygen species (ROS) production, and apoptotic cell death. However, some aspects of this mechanism and the details of the cellular and mitochondrial accumulation of MPP+ are still poorly understood. The aim of this study was to characterize a structural and functional MPP+ mimic which is suitable to study the cellular distribution and mitochondrial uptake of MPP+ in live cells and use it to identify the molecular details of these processes to advance the understanding of the mechanism of the selective dopaminergic toxicity of MPP+ . Here we report the characterization of the fluorescent MPP+ derivative, 1-methyl-4-(4'-iodophenyl)pyridinium (4'I-MPP+ ), as a suitable candidate for this purpose. Using this novel probe, we show that cytosolic/mitochondrial Ca2+ play a critical role through sodium-calcium exchanger (NCX) in the mitochondrial and cellular accumulation of MPP+ suggesting for the first time that MPP+ and related mitochondrial toxins may also exert their toxic effects through the perturbation of Ca2+ homeostasis in dopaminergic cells. We also found that the specific mitochondrial NCX (mNCX) inhibitors protect dopaminergic cells from the MPP+ and 4'I-MPP+ toxicity, most likely through the inhibition of the mitochondrial uptake, which could potentially be exploited for the development of pharmacological agents to protect the central nervous system (CNS) dopaminergic neurons from PD-causing environmental toxinsen_US
dc.language.isoen_USen_US
dc.subjectResearch Subject Categories::NATURAL SCIENCES::Chemistry::Biochemistry::Toxicologyen_US
dc.titleCharacteristics of the mitochondrial and cellular uptake of MPP+ , as probed by the fluorescent mimic, 4'I-MPP+en_US
dc.typeArticleen_US
dc.rights.holderOpen Access articleen_US


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