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Hexachloronaphthalene Induces Mitochondrial-Dependent Neurotoxicity via a Mechanism of Enhanced Production of Reactive Oxygen Species
Joint Authors
Stragierowicz, Joanna
Boczek, Tomasz
Lisek, Malwina
Ferenc, Bozena
Zylinska, Ludmila
Guo, Feng
Prosseda, Philipp P.
Kilanowicz, Anna
Wiktorska, Magdalena
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-06-26
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Hexachloronaphthalene (PCN67) is one of the most toxic among polychlorinated naphthalenes.
Despite the known high bioaccumulation and persistence of PCN67 in the environment, it is still unclear to what extent exposure to these substances may interfere with normal neuronal physiology and lead to neurotoxicity.
Therefore, the primary goal of this study was to assess the effect of PCN67 in neuronal in vitro models.
Neuronal death was assessed upon PCN67 treatment using differentiated PC12 cells and primary hippocampal neurons.
At 72 h postexposure, cell viability assays showed an IC50 value of 0.35 μg/ml and dose-dependent damage of neurites and concomitant downregulation of neurofilaments L and M.
Moreover, we found that younger primary neurons (DIV4) were much more sensitive to PCN67 toxicity than mature cultures (DIV14).
Our comprehensive analysis indicated that the application of PCN67 at the IC50 concentration caused necrosis, which was reflected by an increase in LDH release, HMGB1 protein export to the cytosol, nuclear swelling, and loss of homeostatic control of energy balance.
The blockage of mitochondrial calcium uniporter partially rescued the cell viability, loss of mitochondrial membrane potential (ΔΨm), and the overproduction of reactive oxygen species, suggesting that the underlying mechanism of neurotoxicity involved mitochondrial calcium accumulation.
Increased lipid peroxidation as a consequence of oxidative stress was additionally seen for 0.1 μg/ml of PCN67, while this concentration did not affect ΔΨm and plasma membrane permeability.
Our results show for the first time that neuronal mitochondria act as a target for PCN67 and indicate that exposure to this drug may result in neuron loss via mitochondrial-dependent mechanisms.
American Psychological Association (APA)
Lisek, Malwina& Stragierowicz, Joanna& Guo, Feng& Prosseda, Philipp P.& Wiktorska, Magdalena& Ferenc, Bozena…[et al.]. 2020. Hexachloronaphthalene Induces Mitochondrial-Dependent Neurotoxicity via a Mechanism of Enhanced Production of Reactive Oxygen Species. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1203968
Modern Language Association (MLA)
Lisek, Malwina…[et al.]. Hexachloronaphthalene Induces Mitochondrial-Dependent Neurotoxicity via a Mechanism of Enhanced Production of Reactive Oxygen Species. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1203968
American Medical Association (AMA)
Lisek, Malwina& Stragierowicz, Joanna& Guo, Feng& Prosseda, Philipp P.& Wiktorska, Magdalena& Ferenc, Bozena…[et al.]. Hexachloronaphthalene Induces Mitochondrial-Dependent Neurotoxicity via a Mechanism of Enhanced Production of Reactive Oxygen Species. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1203968
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203968