Secretome Analyses of A尾1鈥?2 Stimulated Hippocampal Astrocytes Reveal that CXCL10 is Involved in Astrocyte Migration
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- 作者：Wenjia Lai ; Jing Wu ; Xiao Zou ; Jian Xie ; Liwei Zhang ; Xuyang Zhao ; Minzhi Zhao ; Qingsong Wang ; Jianguo Ji
- 刊名：Journal of Proteome Research
- 出版年：2013
- 出版时间：February 1, 2013
- 年：2013
- 卷：12
- 期：2
- 页码：832-843
- 全文大小：571K
- 年卷期：v.12,no.2(February 1, 2013)
- ISSN：1535-3907
文摘
Amyloid-beta (A尾) aggregation plays an important role in the development of Alzheimer鈥檚 disease (AD). In the AD brain, amyloid plaques are surrounded by reactive astrocytes, and many essential functions of astrocytes have been reported to be mediated by protein secretion. However, the roles of activated astrocytes in AD progression are under intense debate. To provide an in-depth view of the secretomes of activated astrocytes, we present in this study a quantitative profile of rat hippocampal astrocyte secretomes at multiple time points after both brief and sustained A尾1鈥?2 stimulation. Using SILAC labeling and LC鈥揗S/MS analyses, we identified 19 up-regulated secreted proteins after A尾1鈥?2 treatment. These differentially expressed proteins have been suggested to be involved in key aspects of biological processes, such as cell recruitment, A尾 clearance, and regulation of neurogenesis. Particularly, we validated the role played by CXCL10 in promoting astrocyte aggregation around amyloid plagues through in vitro cell migration analysis. This research provides global, quantitative profiling of astrocyte secretomes produced on A尾 stimulation and hence provides a detailed molecular basis for the relationship between amyloid plaques and astrocyte aggregation; the findings thus have important implications for further investigations into AD development and therapy.