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学科主题: 临床医学
题名:
Aluminum maltolate induces primary rat astrocyte apoptosis via overactivation of the class III PI3K/Beclin 1-dependent autophagy signal
作者: Zeng, Ke-Wu; Fu, Hong; Liu, Geng-Xin; Wang, Xue-Mei
关键词: Astrocyte ; Aluminum ; Autophagy ; Apoptosis
刊名: TOXICOLOGY IN VITRO
发表日期: 2012-03-01
DOI: 10.1016/j.tiv.2011.11.010
卷: 26, 期:2, 页:215-220
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Toxicology
研究领域[WOS]: Toxicology
关键词[WOS]: ALZHEIMERS-DISEASE ; CELL-LINES ; NEURODEGENERATIVE DISORDERS ; CULTURED ASTROCYTES ; NEURAL ORIGIN ; NEUROBLASTOMA ; NEURONS ; DEATH ; NEUROTOXICITY ; TOXICITY
英文摘要:

Aluminum-induced neuronal cell apoptosis has been implicated in various neurodegenerative disorders. However, whether autophagy, a vital lysosomal degradation pathway, is involved in this pathogenesis still remains unknown. Our present findings demonstrated that aluminum significantly increased rat astrocyte apoptosis and autophagy levels in a dose-dependent manner. Examination of the associated mechanisms revealed that aluminum at low levels (400 MM) did not increase apoptosis protein expressions (cleaved caspase-3 and cleaved PARP), but markedly up-regulated autophagy-related protein Beclin 1 expression. This indicates that the autophagy process occurs earlier than neuronal apoptosis. Moreover, aluminum at high levels (1600 MM) significantly induced autophagy-related protein (Beclin 1 and LC3II) and apoptosis-related protein expressions, showing that both autophagy and apoptosis processes are activated under high levels of aluminum exposure. We used 3-methyladenine, an inhibitor of class Ill phosphatidylinositol-3 kinase, to treat astrocytes and found that the apoptosis rate in the 3-MA/aluminum co-treated group was markedly down-regulated compared with aluminum alone-treated astrocytes. The apoptosis protein and autophagy-related protein expressions were also decreased. These observations showed that the mild autophagy process may precede apoptosis in low dose aluminum-insulted astrocytes, and high dose aluminum-induced serious autophagy may result in cell apoptosis via the Beclin 1-dependent autophagy signal pathway. (C) 2011 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 30973813 ; 30672760 ; 20070001707
项目资助者: National Natural Science Foundation of China ; Ministry of Education, China
WOS记录号: WOS:000301019600004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65959
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: Peking Univ, Hosp 1, Res Studio Integrat Tradit & Western Med, Beijing 100034, Peoples R China

Recommended Citation:
Zeng, Ke-Wu,Fu, Hong,Liu, Geng-Xin,et al. Aluminum maltolate induces primary rat astrocyte apoptosis via overactivation of the class III PI3K/Beclin 1-dependent autophagy signal[J]. TOXICOLOGY IN VITRO,2012,26(2):215-220.
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