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凋亡小体:形成机制、分离方法及其功能相关性。

Apoptotic Bodies: Mechanism of Formation, Isolation and Functional Relevance.

机构信息

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.

Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

出版信息

Subcell Biochem. 2021;97:61-88. doi: 10.1007/978-3-030-67171-6_4.

DOI:10.1007/978-3-030-67171-6_4
PMID:33779914
Abstract

In the final stages of apoptosis, apoptotic cells can generate a variety of membrane-bound vesicles known as apoptotic extracellular vesicles (ApoEVs). Apoptotic bodies (ApoBDs), a major subset of ApoEVs, are formed through a process termed apoptotic cell disassembly characterised by a series of tightly regulated morphological steps including plasma membrane blebbing, apoptotic membrane protrusion formation and fragmentation into ApoBDs. To better characterise the properties of ApoBDs and elucidate their function, a number of methods including differential centrifugation, filtration and fluorescence-activated cell sorting were developed to isolate ApoBDs. Furthermore, it has become increasingly clear that ApoBD formation can contribute to various biological processes such as apoptotic cell clearance and intercellular communication. Together, recent literature demonstrates that apoptotic cell disassembly and thus, ApoBD formation, is an important process downstream of apoptotic cell death. In this chapter, we discuss the current understandings of the molecular mechanisms involved in regulating apoptotic cell disassembly, techniques for ApoBD isolation, and the functional roles of ApoBDs in physiological and pathological settings.

摘要

在细胞凋亡的最后阶段,凋亡细胞可以产生多种膜结合囊泡,称为凋亡细胞外囊泡(ApoEVs)。凋亡小体(ApoBDs)是 ApoEVs 的主要亚群,通过称为凋亡细胞解体的过程形成,该过程的特征是一系列紧密调控的形态步骤,包括质膜起泡、凋亡膜突起形成和碎裂成 ApoBDs。为了更好地描述 ApoBDs 的特性并阐明其功能,已经开发了包括差速离心、过滤和荧光激活细胞分选在内的多种方法来分离 ApoBDs。此外,越来越明显的是,ApoBD 的形成可以促进各种生物学过程,如凋亡细胞清除和细胞间通讯。总之,最近的文献表明,凋亡细胞解体,从而 ApoBD 的形成,是凋亡细胞死亡下游的一个重要过程。在本章中,我们讨论了调节凋亡细胞解体的分子机制、ApoBD 分离技术以及 ApoBD 在生理和病理环境中的功能作用的当前认识。

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本文引用的文献

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Metabolites released from apoptotic cells act as tissue messengers.凋亡细胞释放的代谢物作为组织信使发挥作用。
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Emerging technologies towards extracellular vesicles large-scale production.用于细胞外囊泡大规模生产的新兴技术。
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Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis.定义细胞骨架成分在细胞凋亡过程中凋亡足和凋亡小体形成中的作用。
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Mature osteoclast-derived apoptotic bodies promote osteogenic differentiation via RANKL-mediated reverse signaling.成熟破骨细胞来源的凋亡小体通过 RANKL 介导的逆向信号促进成骨分化。
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Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs.凋亡的内皮细胞释放装载有免疫刺激性病毒样 RNA 的小型细胞外囊泡。
Sci Rep. 2019 May 10;9(1):7203. doi: 10.1038/s41598-019-43591-y.
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ROCK1 but not LIMK1 or PAK2 is a key regulator of apoptotic membrane blebbing and cell disassembly.ROCK1 而非 LIMK1 或 PAK2 是调控凋亡细胞膜泡形成和细胞解体的关键调节因子。
Cell Death Differ. 2020 Jan;27(1):102-116. doi: 10.1038/s41418-019-0342-5. Epub 2019 May 1.
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Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance.干细胞增殖是由上皮组织维持过程中死亡细胞的凋亡小体诱导的。
Nat Commun. 2019 Mar 5;10(1):1044. doi: 10.1038/s41467-019-09010-6.
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Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes.Gasdermin E 并未通过促进 Jurkat T 细胞和 THP-1 单核细胞早期发生继发性坏死来限制细胞凋亡解体。
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