An Argonaute 2 switch regulates circulating miR-210 to coordinate hypoxic adaptation across cells.
An Argonaute 2 switch regulates circulating miR-210 to coordinate hypoxic adaptation across cells.
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DOI：
10.1016/j.bbamcr.2014.06.012
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发表时间：
2014-11
影响因子：
5.1
通讯作者：
Chan, Stephen Y.
中科院分区：
文献类型：
--
作者：
Hale, Andrew;Lee, Changjin;Annis, Sofia;Min, Pil-Ki;Pande, Reena;Creager, Mark A.;Julian, Colleen G.;Moore, Lorna G.;Mitsialis, S. Alex;Hwang, Sarah J.;Kourembanas, Stella;Chan, Stephen Y.
复杂生物体可能通过跨多个组织的特殊通信途径协调对缺氧的分子反应，但这些机制尚不清楚。基于血浆的细胞外microrna已经被描述，然而，它们在缺氧中的调节和生物学功能仍然是谜。我们发现了缺氧和再氧细胞中缺氧诱导的microRNA-210 （miR-210）释放的独特模式。在生理和病理条件下，这种microRNA在人血浆中的需氧量和输送量也会升高。释放的miR-210可以传递到受体细胞，其对直接靶细胞ISCU和线粒体代谢的直接抑制主要表现在缺氧中。为了调节这些缺氧特异性作用，Argonaute 2的脯氨酸羟基化作为一个分子开关，在miR-210递送后，在源细胞中相互调节miR-210的释放和细胞内活性，并调节受体细胞的细胞内活性。因此，Argonaute 2依赖性控制释放的miR-210代表了一种独特的通信系统，该系统整合了解剖学上不同细胞的缺氧反应，防止了正常氧下递送的miR-210的不必要活性，同时仍为受体组织准备早期缺氧应激并加速适应。
Complex organisms may coordinate molecular responses to hypoxia by specialized avenues of communication across multiple tissues, but these mechanisms are poorly understood. Plasma-based, extracellular microRNAs have been described, yet, their regulation and biological functions in hypoxia remain enigmatic. We found a unique pattern of release of the hypoxia-inducible microRNA-210 (miR-210) from hypoxic and reoxygenated cells. This microRNA is also elevated in human plasma in physiologic and pathologic conditions of altered oxygen demand and delivery. Released miR-210 can be delivered to recipient cells, and its direct suppression of its direct target ISCU and mitochondrial metabolism is primarily evident in hypoxia. To regulate these hypoxia-specific actions, prolyl-hydroxylation of Argonaute 2 acts as a molecular switch that reciprocally modulates miR-210 release and intracellular activity in source cells as well as regulates intracellular activity in recipient cells after miR-210 delivery. Therefore, Argonaute 2-dependent control of released miR-210 represents a unique communication system that integrates the hypoxic response across anatomically distinct cells, preventing unnecessary activity of delivered miR-210 in normoxia while still preparing recipient tissues for incipient hypoxic stress and accelerating adaptation.
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影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
DOI：
10.4161/cc.9.6.11006
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Chan SY;Loscalzo J
通讯作者：
Loscalzo J
DOI：
10.2174/187153007781662585
发表时间：
2007-09-01
影响因子：
1.9
作者：
Bolte, Craig S.;Liao, Siyun;Schultz, Jo El J.
通讯作者：
Schultz, Jo El J.
影响因子：
4
作者：
Heneghan, Helen M.;Miller, Nicola;Kerin, Michael J.
通讯作者：
Kerin, Michael J.
影响因子：
20.3
作者：
Laffont, Benoit;Corduan, Aurelie;Provost, Patrick
通讯作者：
Provost, Patrick