Hexachloronaphthalene Induces Mitochondrial-Dependent Neurotoxicity via a Mechanism of Enhanced Production of Reactive Oxygen Species

Oxidative Medicine and Cellular Longevity
Malwina LisekTomasz Boczek

Abstract

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 over...Continue Reading

References

Jul 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·L A Greene, A S Tischler
May 19, 1995·Neuroscience Letters·W G Angus, M L Contreras
Oct 1, 1997·American Journal of Industrial Medicine·W PoppJ Theisen
Mar 7, 1998·Journal of Toxicology and Environmental Health. Part a·C Weistrand, K Norén
Apr 16, 1998·Archives of Environmental Contamination and Toxicology·A Lundén, K Norén
Aug 19, 2000·Archives of Environmental Contamination and Toxicology·D L VilleneuveJ P Giesy
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 12, 2002·Nature·Paola ScaffidiMarco E Bianchi
Oct 3, 2002·Journal of Neurochemistry·Anatoly A StarkovGary Fiskum
Apr 2, 2004·Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering·Y HoriiN Yamashita
Apr 20, 2004·Environmental Pollution·J Falandysz
May 12, 2004·Developmental Biology·Hongtao Qin, Jo Anne Powell-Coffman
Mar 17, 2006·Human & Experimental Toxicology·A GalochA Kilanowicz
Aug 22, 2006·Developmental Neuroscience·C P TurnerZ C Berry
Dec 5, 2006·Trends in Biochemical Sciences·Pierre Golstein, Guido Kroemer
May 31, 2007·Environmental Science & Technology·Sum Chi LeeKevin C Jones
Oct 30, 2007·Cerebral Cortex·Nicolas HeckHeiko J Luhmann
Jul 24, 2008·Dose-response : a Publication of International Hormesis Society·John F ReichardAlvaro Puga
Aug 30, 2008·Ecotoxicology and Environmental Safety·Anna KilanowiczAdam Daragó
Jan 6, 2009·Environmental Toxicology and Pharmacology·Howard P GlauertBrett T Spear
Mar 17, 2009·Chemosphere·Anna OrlikowskaJerzy Falandysz
Sep 29, 2009·Ecotoxicology and Environmental Safety·Anna Kilanowicz, Malgorzata Skrzypinska-Gawrysiak
Feb 4, 2010·PloS One·Jaehoon ChungShinya Kuroda
Jan 1, 2009·International Journal of Alzheimer's Disease·M MancusoG Siciliano
Nov 3, 2010·Ecotoxicology and Environmental Safety·Anna KilanowiczAndrzej Sapota
Nov 1, 2005·Environmental Toxicology and Pharmacology·Hanna VinitskayaLudmila Zylinska
Jan 25, 2012·TheScientificWorldJournal·Kandaswamy SelvakumarJagadeesan Arunakaran
Mar 6, 2012·Neurotoxicology·Anna KilanowiczWieslaw Szymczak

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