title: Neuroprotective effects of tert-butylhydroquinone on paraquat-induced dopaminergic cell degeneration in C57BL/6 mice and in PC12 cells.
abstract: The present study was aimed at determining the role of paraquat (PQ) in the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway and the possible neuroprotective effects of tert-butylhydroquinone (tBHQ) pretreatment on PQ-induced neurodegeneration in vivo and in vitro. 7 mg/kg PQ treatment of male C57BL/6 mice caused decreased spontaneous locomotor activity, decreased tyrosine hydroxylase (TH)-positive neurons, increased terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL)-positive cells in the substantia nigra, as well as increased protein levels of both nuclear Nrf2 and HO-1. In PQ-treated mice, pretreatment with 1 % tBHQ (w/w) significantly attenuated impairments in behavioral performance, decreased TH-positive neurons, and increased TUNEL-positive cells in the substantia nigra, as well as increased protein expression of both nuclear Nrf2 and HO-1. Pretreatment with 40 μM tBHQ protected PC12 cells against 100 and 300 μM PQ-mediated cytotoxicity. The dual-luciferase reporter gene also revealed that the transcriptional activation of HO-1 gene expression of the antioxidant responsive element via Nrf2 occurred as a consequence of 100 and 300 μM PQ exposure. Collectively, these results clearly indicated for the first time that the Nrf2/HO-1 pathway in the substantia nigra was activated by PQ, and pretreatment with tBHQ conferred neuroprotection against PQ-induced Parkinsonism presumably by increasing Nrf2 and HO-1 expression.
authors.affiliation: Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, Fuzhou, China. fmulhy@163.com
authors.forename: Huangyuan
authors.initials: H
authors.lastname: Li
authors.forename: Siying
authors.initials: S
authors.lastname: Wu
authors.forename: Zhangjing
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Chenzi
authors.initials: C
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D006873:Hydroquinones; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; C018855:2-tert-butylhydroquinone; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D010269:Paraquat