期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 452, 期 1-2, 页码 95-104出版社
SPRINGER
DOI: 10.1007/s11010-018-3415-8
关键词
Zinc; Nigrostriatal dopaminergic neurodegeneration; Oxidative stress; Glutathione S-transferase-pi
类别
资金
- Council of Scientific and Industrial Research (CSIR), New Delhi
- Department of Science and Technology (DST), New Delhi
- University Grants Commission (UGC), New Delhi
- CSIR through CSIR-network programme 'Integrated NextGen Approaches in Health, Disease and Environmental Toxicity' [INDEPTH (BSC-0111)]
Oxidative stress is recognized as one of the major wrongdoers in Parkinson's disease (PD) while glutathione S-transferase (GST), an endogenous antioxidant, protects from oxidative stress-induced neurodegeneration. Despite GST-pi (GST-) encounters the toxic manifestations in PD, its role in zinc (Zn)-induced nigrostriatal dopaminergic neurodegeneration remains elusive. The study aimed to explore the role of GST- in Zn-induced Parkinsonism and its underlying molecular mechanism. Male Wistar rats were treated intraperitoneally with zinc (zinc sulfate), twice a week, for 2-12 weeks. GST- inducer, benzyl isothiocyanate (BITC) was also administered in a few sets of experiments along with respective vehicle. Catalytic activity and expression of GST- protein, total GST activity, neurobehavioral indexes, striatal dopamine and its metabolites, nigral tyrosine hydroxylase (TH)-positive neurons and expression of TH and B-cell lymphoma-2 (Bcl-2) proteins were reduced in Zn-treated rats. Conversely, oxidative stress indicators, c-jun N-terminal kinase (JNK) activation, c-jun phosphorylation, cytochrome c release, Bcl-2-associated X protein (Bax) translocation, and procaspase 3/9 to caspase 3/9 conversion were significantly increased in Zn-exposed rats. BITC ameliorated GST- activity/expression and normalized Zn-induced changes in neurodegenerative indicators, oxidative stress, JNK activation, c-jun phosphorylation and apoptotic indexes. The results demonstrate that Zn inhibits GST- expression leading to increased oxidative stress and JNK activation, which induce apoptosis thereby degeneration of the nigrostriatal dopaminergic neurons.
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