期刊
NATURE CHEMISTRY
卷 6, 期 10, 页码 885-892出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.2021
关键词
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资金
- National Creative Research Initiative program in Korea [2010-0018272]
- Office of Basic Energy Sciences, US Department of Energy [DE-FG02-01ER15186]
- Engineering and Physical Sciences Research Council [EP/J009687/1]
- European Union for a Marie Curie Career Integration grant
- Chemical Biology Research Center in Korea Research Institute of Bioscience and Biotechnology
- U.S. Department of Energy (DOE) [DE-FG02-01ER15186] Funding Source: U.S. Department of Energy (DOE)
- EPSRC [EP/J009687/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/J009687/1] Funding Source: researchfish
- National Research Foundation of Korea [21A20131312351] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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