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

被引:12
作者
Sharma, Heera [1 ]
Hirko, Aaron C. [2 ]
King, Michael A. [2 ]
Liu, Bin [1 ]
机构
[1] Univ Florida, Dept Pharmacodynam, Coll Pharm, Gainesville, FL 32610 USA
[2] Univ Florida, Dept Pharmacol & Therapeut, Coll Med, Gainesville, FL 32610 USA
关键词
Dopamine; ROS; NADPH oxidase; Pesticide; Combination; Neurotoxicity; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-C; PARKINSONS-DISEASE; MITOCHONDRIAL DYSFUNCTION; SUBSTANTIA-NIGRA; OXIDATIVE DAMAGE; ANGIOTENSIN-II; CROSS-TALK; PHARMACOLOGICAL INHIBITION; MICROGLIAL ACTIVATION;
D O I
10.1016/j.toxlet.2018.09.006
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 p67(Phox )in N27 neurons. Furthermore, treatment with dieldrin and lindane upregulated the cellular expression of Nox1 but not p67(Phox) 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 p67(Phox )proteins indicated colocalization of both subunits with mitochondria in untreated cells. Treatment with dieldrin and lindane further increased mitochondrial colocalization of Noxl 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.
引用
收藏
页码:47 / 55
页数:9
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