小柯机器人

凋亡细胞代谢物可充当组织信使
2020-03-19 13:03

美国弗吉尼亚大学Kodi S. Ravichandran及其课题组的最新研究发现凋亡细胞释放的代谢物可充当组织信使。相关论文在线发表在2020年3月18日出版的《自然》杂志上。

研究人员分析了凋亡细胞的代谢产物分泌组,并确定了其对相邻组织的影响。研究显示凋亡的淋巴细胞和巨噬细胞释放特定的代谢产物,同时保留了膜完整性。利用不同刺激诱导细胞凋亡后,这些代谢物子集也在不同的原代细胞和细胞系中共享。从机制上讲,细胞凋亡的代谢物分泌物组不仅是细胞内容物的被动排空,还是受调控的过程。

含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)介导的pannexin 1通道在细胞质膜上开放促进了部分代谢物的释放。另外,某些代谢途径在凋亡过程中仍保持活性,并且从给定途径中仅释放选择的代谢物。从功能上讲,细胞凋亡的代谢物分泌组在健康邻近细胞中诱导了特定的基因程序,包括抑制炎症、细胞增殖和伤口愈合。

此外,在炎症性关节炎和肺移植排斥反应的小鼠模型中,凋亡代谢混合物降低了疾病严重程度。该研究提出了一个新概念:凋亡细胞不是等待清除的无用细胞,而是通过释放代谢产物作为“再见”信号来主动调节组织输出。

据介绍,在体内Caspase依赖的细胞凋亡约占稳态细胞更新的90%并调节炎症、细胞增殖和组织再生。凋亡细胞如何调控这些多样的功能亟待阐明。

附:英文原文

Title: Metabolites released from apoptotic cells act as tissue messengers

Author: Christopher B. Medina, Parul Mehrotra, Sanja Arandjelovic, Justin S. A. Perry, Yizhan Guo, Sho Morioka, Brady Barron, Scott F. Walk, Bart Ghesquire, Alexander S. Krupnick, Ulrike Lorenz, Kodi S. Ravichandran

Issue&Volume: 2020-03-18

Abstract: Caspase-dependent apoptosis accounts for approximately 90% of homeostatic cell turnover in the body1, and regulates inflammation, cell proliferation, and tissue regeneration2,3,4. How apoptotic cells mediate such diverse effects is not fully understood. Here we profiled the apoptotic metabolite secretome and determined its effects on the tissue neighbourhood. We show that apoptotic lymphocytes and macrophages release specific metabolites, while retaining their membrane integrity. A subset of these metabolites is also shared across different primary cells and cell lines after the induction of apoptosis by different stimuli. Mechanistically, the apoptotic metabolite secretome is not simply due to passive emptying of cellular contents and instead is a regulated process. Caspase-mediated opening of pannexin 1 channels at the plasma membrane facilitated the release of a select subset of metabolites. In addition, certain metabolic pathways continued to remain active during apoptosis, with the release of only select metabolites from a given pathway. Functionally, the apoptotic metabolite secretome induced specific gene programs in healthy neighbouring cells, including suppression of inflammation, cell proliferation, and wound healing. Furthermore, a cocktail of apoptotic metabolites reduced disease severity in mouse models of inflammatory arthritis and lung-graft rejection. These data advance the concept that apoptotic cells are not inert cells waiting for removal, but instead release metabolites as ‘good-bye’ signals to actively modulate outcomes in tissues.

DOI: 10.1038/s41586-020-2121-3

Source: https://www.nature.com/articles/s41586-020-2121-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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