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Previous Article | Next Article
The Journal of Neuroscience, September 1, 2002, 22(17):7408-7416
In Vitro Neurotoxicity of Methylisothiazolinone, a Commonly Used Industrial and Household Biocide, Proceeds via a Zinc and Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent Pathway
Shen Du, BethAnn McLaughlin, Sumon Pal, and Elias Aizenman Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Neurodegenerative disorders in humans may be triggered or exacerbated by exposure to occupational or environmental agents. Here, we show that a brief exposure to methylisothiazolinone, a widely used industrial and household biocide, is highly toxic to cultured neurons but not to glia. We also show that the toxic actions of this biocide are zinc dependent and require the activation of p44/42 extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated pathway. The cell death process also involves activation of NADPH oxidase, generation of reactive oxygen species, DNA damage, and overactivation of poly(ADP-ribose) polymerase, all occurring downstream from ERK phosphorylation. The toxic effects of methylisothiazolinone and related biocides on neurons have not been reported previously. Because of their widespread use, the neurotoxic consequences of both acute and chronic human exposure to these toxins need to be evaluated.
Key words: neurotoxicity; isothiazolone; biocide; oxidation; necrosis; zinc; glutathione; ERK; lipoxygenase; NADPH oxidase; PARP
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177408-09$05.00/0
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