Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells = 인공 염소이온 운반체를 이용한 세포 자살 물질 개발

Cited 241 time in scopus
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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
Author(s)
Sung-Kyun Ko; S K Kim; A Share; V M Lynch; J Park; W Namkung; W V Rossom; N Busschaert; P A Gale; J L Sessler; I Shin
Bibliographic Citation
Nature Chemistry, vol. 6, no. 10, pp. 885-892
Publication Year
2014
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
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/nchem.2021
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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