标题:Tert-butylhydroquinone protects PC12 cells against ferrous sulfate-induced oxidative and inflammatory injury via the Nrf2/ARE pathway
作者:Xu, Wenzhe; Li, Feng; Xu, Zhenkuan; Sun, Bin; Cao, Jingwei; Liu, Yuguang
作者机构:[Li, Feng; Liu, Yuguang] Shandong Univ, Dept Neurosurg, Qilu Hosp, Jinan 250012, Shandong, Peoples R China.; Shandong Univ, Brain Sci Res Inst, Jina 更多
通讯作者:Li, F;Liu, YG
通讯作者地址:[Li, F; Liu, YG]Shandong Univ, Dept Neurosurg, Qilu Hosp, Jinan 250012, Shandong, Peoples R China.
来源:CHEMICO-BIOLOGICAL INTERACTIONS
出版年:2017
卷:273
页码:28-36
DOI:10.1016/j.cbi.2017.05.021
关键词:Neurodegenerative diseases; PC12 cells; Tert-butylhydroquinone;; Oxidative stress; Inflammation; Apoptosis
摘要:Increasing evidence had proved the critical role of iron in the pathogenesis of numerous neurodegenerative diseases because of its capacity to promote the formation of reactive oxygen species (ROS). Tertbutylhydroquinone (tBHQ) was a metabolite of butylated hydroxyanisole, a widely used food antioxidant. This study was aimed to investigate the protective effects of tBHQ on a cellular model of neurodegenerative disease, which was established in PC12 cells by exposure to ferrous sulfate (FS), and elucidate the potential protective mechanisms. The results showed that FS exposure increased lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by significant increases in the bax/bcl-2 ratio, cytochrome c release, and caspase-3 cleavage. It also enhanced the ROS production, malondialdehyde (MDA) content (lipid peroxidation), gamma-H2A.X formation (DNA damage), and promoted nuclear factor kappa B (NF-kappa B) activation and expressions of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). tBHQ pretreatment alleviated FS-induced LDH release, cell apoptosis, oxidative stress and inflammatory response by promoting Nrf2 nuclear translocation and the protein levels of Nrf2 downstream target genes heme oxygenase-1 (Hmox-1), nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase-1 (Nqo1) and glutathione peroxidase-1 (Gpx1). tBHQ alleviated the FS-induced LDH release in control siRNA-treated PC12 cells, but failed to alleviate FS-induced LDH release in Nrf2 siRNA-treated cells. These findings suggested that pretreatment with tBHQ protected PC12 cells from FS-induced oxidative and inflammatory injury via the Nrf2/ARE pathway. tBHQ was promising as a potential therapeutic agent for neurodegenerative diseases induced by iron toxicity and should be encouraged for further research. (C) 2017 Elsevier B.V. All rights reserved.
收录类别:SCOPUS;SCIE
WOS核心被引频次:4
Scopus被引频次:4
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020275282&doi=10.1016%2fj.cbi.2017.05.021&partnerID=40&md5=9a81d5de22de1d1563b798d2f1a61054
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