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Title 

Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells

 

인공 염소이온 운반체를 이용한 세포 자살 물질 개발

Authors 

Sung-Kyun KoS K KimA ShareV M LynchJ ParkW NamkungW V RossomN BusschaertP A GaleJ L SesslerI Shin

Publisher 

Nature Publishing Group

Issue Date 

2014

Citation 

Nature Chemistry, vol. 6, no. 10, pp. 885-892

Abstract 

Anion transporters based on small molecules have received attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis. However, a direct correlation between a change in cellular chloride anion concentration and cytotoxicity has not been established for synthetic ion carriers. Here we show that two pyridine diamide-strapped calix[4]pyrroles induce coupled chloride anion and sodium cation transport in both liposomal models and cells, and promote cell death by increasing intracellular chloride and sodium ion concentrations. Removing either ion from the extracellular media or blocking natural sodium channels with amiloride prevents this effect. Cell experiments show that the ion transporters induce the sodium chloride influx, which leads to an increased concentration of reactive oxygen species, release of cytochrome c from the mitochondria and apoptosis via caspase activation. However, they do not activate the caspase-independent apoptotic pathway associated with the apoptosis-inducing factor. Ion transporters, therefore, represent an attractive approach for regulating cellular processes that are normally controlled tightly by homeostasis.

ISSN 

1755-4330

Link 

http://dx.doi.org/10.1038/nchem.2021

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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