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学科主题: 药学
题名:
Gadolinium-induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons
作者: Xia, Qing1; Feng, Xudong; Huang, Haifeng; Du, Lingyan; Yang, Xiaoda; Wang, Kui
关键词: endoplasmic reticulum stress ; gadolinium ; neurotoxicity ; oxidative stress
刊名: JOURNAL OF NEUROCHEMISTRY
发表日期: 2011-04-01
DOI: 10.1111/j.1471-4159.2010.07162.x
卷: 117, 期:1, 页:38-47
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Neurosciences
研究领域[WOS]: Biochemistry & Molecular Biology ; Neurosciences & Neurology
关键词[WOS]: UNFOLDED-PROTEIN RESPONSE ; NEPHROGENIC SYSTEMIC FIBROSIS ; CELL-DEATH ; ER STRESS ; INDUCED APOPTOSIS ; CALCIUM HOMEOSTASIS ; NEUROTROPHIC FACTOR ; IN-VIVO ; ALUMINUM ; BRAIN
英文摘要:

P>Introduction of Gadolinium (Gd) to the nervous system is linked to the development of neurotoxicity involving both oxidative and endoplasmic reticulum (ER) stress. Gd levels (0.2-20 mu m) in the form of gadolinium trichloride (GdCl(3)) cause neurotoxicity in vitro. We investigated the signaling pathways in primary cultured rat cortical neurons and tested whether GdCl(3) induced oxidative and ER stress. Results showed that Gd-induced neural cell death followed a rapid accumulation of intracellular reactive oxygen species. In addition, Gd exposure resulted in spliced X-box binding protein 1 mRNA and increased expression of binding immunoglobulin protein, thus activating transcription factor 4 (ATF4), ATF6, and C/EBP homologous protein mRNA. Up-regulated expression of binding immunoglobulin protein is a hallmark of ER stress and C/EBP homologous protein is an ER stress-related pro-apoptotic transcription factor. Activation of ER stress downstream substrates, inositol-requiring kinase 1 and ATF6, was also observed in Gd-treated cells. The neurotoxic effects of Gd were blocked by the antioxidant N-acetylcysteine. Results demonstrated that Gd-induced cytotoxicity in neurons occurs via oxidative injury and ER stress-related signal transduction, thus offering new insight into the neurotoxicology of gadolinium.

语种: 英语
所属项目编号: 20901005 ; 20637010
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000288264300004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54216
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Biol Chem, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Xia, Qing,Feng, Xudong,Huang, Haifeng,et al. Gadolinium-induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons[J]. JOURNAL OF NEUROCHEMISTRY,2011,117(1):38-47.
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