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鉴定非凋亡程序性细胞死亡中的新型调节剂和蛋白改变。

Identification of new modulators and protein alterations in non-apoptotic programmed cell death.

机构信息

Buck Institute for Age Research, Novato, California 94945, USA.

出版信息

J Cell Biochem. 2010 Dec 15;111(6):1401-12. doi: 10.1002/jcb.22870.

Abstract

This study describes the first proteomic analysis of paraptosis--a non-apoptotic form of programmed cell death. As with apoptosis, the first description of paraptosis was based on morphological criteria. Since there are no known markers for paraptosis, the purpose of this study was to dissect changes in the proteome profile occurring during paraptosis. Using one- and two-dimensional SDS-PAGE, Western analysis, and mass spectrometry, we show that during paraptosis, alterations occur mainly in cytoskeletal proteins, signal transduction proteins, mitochondrial proteins, and some metabolic proteins. We also report the identification of: (1) a paraptosis inhibitor, phosphatidylethanolamine binding protein (PEBP-1), and (2) a candidate mediator of paraptosis, prohibitin. Identification of specific paraptotic changes will ultimately lead to tools to detect this type of programmed cell death in in vivo systems and allow for its further characterization.

摘要

这项研究描述了细胞程序性死亡的非细胞凋亡形式——细胞自噬的首次蛋白质组学分析。与细胞凋亡一样,细胞自噬的首次描述也是基于形态学标准。由于目前还没有细胞自噬的已知标志物,因此本研究的目的是剖析细胞自噬过程中蛋白质组图谱的变化。通过使用一维和二维 SDS-PAGE、Western 分析和质谱分析,我们表明,在细胞自噬过程中,主要发生在细胞骨架蛋白、信号转导蛋白、线粒体蛋白和一些代谢蛋白中的变化。我们还报告了以下内容的鉴定:(1)细胞自噬抑制剂,磷脂酰乙醇胺结合蛋白(PEBP-1)和(2)细胞自噬的候选介质,抑素。鉴定特定的细胞自噬变化最终将导致在体内系统中检测这种类型的细胞程序性死亡的工具,并允许进一步对其进行表征。

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