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电化学调节一氧化碳介导的细胞信号转导。

Electrochemical Modulation of Carbon Monoxide-Mediated Cell Signaling.

机构信息

Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Research Laboratory of Electronics and McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

出版信息

Angew Chem Int Ed Engl. 2021 Sep 6;60(37):20325-20330. doi: 10.1002/anie.202103228. Epub 2021 Aug 11.

Abstract

Despite the critical role played by carbon monoxide (CO) in physiological and pathological signaling events, current approaches to deliver this messenger molecule are often accompanied by off-target effects and offer limited control over release kinetics. To address these challenges, we develop an electrochemical approach that affords on-demand release of CO through reduction of carbon dioxide (CO ) dissolved in the extracellular space. Electrocatalytic generation of CO by cobalt phthalocyanine molecular catalysts modulates signaling pathways mediated by a CO receptor soluble guanylyl cyclase. Furthermore, by tuning the applied voltage during electrocatalysis, we explore the effect of the CO release kinetics on CO-dependent neuronal signaling. Finally, we integrate components of our electrochemical platform into microscale fibers to produce CO in a spatially-restricted manner and to activate signaling cascades in the targeted cells. By offering on-demand local synthesis of CO, our approach may facilitate the studies of physiological processes affected by this gaseous molecular messenger.

摘要

尽管一氧化碳(CO)在生理和病理信号事件中起着关键作用,但目前传递这种信使分子的方法往往伴随着脱靶效应,并对释放动力学的控制有限。为了解决这些挑战,我们开发了一种电化学方法,通过还原细胞外空间中溶解的二氧化碳(CO )来按需释放 CO。钴酞菁分子催化剂的电催化生成 CO 调节由 CO 受体可溶性鸟苷酸环化酶介导的信号通路。此外,通过在电催化过程中调节施加的电压,我们研究了 CO 释放动力学对 CO 依赖性神经元信号的影响。最后,我们将电化学平台的组件集成到微尺度纤维中,以局部受限的方式产生 CO 并激活靶细胞中的信号级联。通过按需局部合成 CO,我们的方法可以促进受这种气态分子信使影响的生理过程的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c008/8405587/1db689dff5ce/nihms-1725738-f0002.jpg

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