Role of NADPH oxidase in cooperative reactive oxygen species generation in dopaminergic neurons induced by combined treatment with dieldrin and lindane.

Abstract:

:Environmental exposure to the highly persistent chlorinated pesticides including dieldrin and lindane is postulated to be a risk factor to the development of Parkinson's disease, a devastating movement disorder. We have previously reported that the combined treatment with dieldrin and lindane induces a cooperative toxicity in the rat N27 dopaminergic neuronal cells through increased oxidative stress and mitochondrial dysfunction. In this study, we investigated the involvement of NADPH oxidase (NOX) proteins in the combined treatment with dieldrin and lindane-induced dopaminergic neurotoxicity. Immunoblot analysis demonstrated the presence of NADPH Oxidase 1 (Nox1) isoform and p67phox in N27 neurons. Furthermore, treatment with dieldrin and lindane upregulated the cellular expression of Nox1 but not p67phox protein. Functionally, dieldrin and lindane-induced ROS production was attenuated, in a dose-dependent manner, by Nox inhibitors diphenylene iodonium and apocynin. Subcellular localization analysis of Nox1 and p67phox proteins indicated colocalization of both subunits with mitochondria in untreated cells. Treatment with dieldrin and lindane further increased mitochondrial colocalization of Nox1 protein, suggesting a potentially prominent role for mitochondrial Nox1 protein in dieldrin and lindane-induced ROS generation in dopaminergic neurons and its contribution to the combined organochlorinated pesticide-induced neurotoxicity.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Sharma H,Hirko AC,King MA,Liu B

doi

10.1016/j.toxlet.2018.09.006

subject

Has Abstract

pub_date

2018-12-15 00:00:00

pages

47-55

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(18)31899-X

journal_volume

299

pub_type

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