A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations.
A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations.
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DOI：
10.1038/nchem.2706
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发表时间：
2017-07
期刊：
影响因子：
21.8
通讯作者：
Shin I
中科院分区：
文献类型：
--
作者：
Busschaert N;Park SH;Baek KH;Choi YP;Park J;Howe ENW;Hiscock JR;Karagiannidis LE;Marques I;Félix V;Namkung W;Sessler JL;Gale PA;Shin I
细胞氯浓度的扰动会影响细胞pH值和自噬并导致细胞凋亡的发生。考虑到这一点，合成离子转运蛋白已被用于干扰细胞离子稳态，从而诱导细胞死亡;然而，尚不清楚合成离子转运蛋白是否也可以用于破坏自噬。在这里，我们表明，方酰胺为基础的离子转运增强脂质体模型中的氯阴离子的运输，并促进氯化钠流入胞质溶胶。方酰胺的脂质体和细胞转运活性显示与细胞死亡活性相关，这归因于半胱天冬酶依赖性细胞凋亡。一种离子转运蛋白还显示引起溶酶体pH的额外变化，这导致溶酶体酶活性受损和自噬过程中断。这种破坏与离子转运蛋白启动细胞凋亡无关。这项研究提供了第一个实验证据，合成离子转运蛋白可以破坏自噬和诱导凋亡。
Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.
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影响因子：
15
作者：
Busschaert, Nathalie;Wenzel, Marco;Light, Mark E.;Iglesias-Hernandez, Paulina;Perez-Tomas, Ricardo;Gale, Philip A.
通讯作者：
Gale, Philip A.
影响因子：
8.4
作者：
Busschaert N;Elmes RB;Czech DD;Wu X;Kirby IL;Peck EM;Hendzel KD;Shaw SK;Chan B;Smith BD;Jolliffe KA;Gale PA
通讯作者：
Gale PA
DOI：
10.1085/jgp.201110596
发表时间：
2011-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
DiCiccio JE;Steinberg BE
通讯作者：
Steinberg BE
影响因子：
3.7
作者：
Creasy, Blaine M.;Hartmann, Constance B.;McCoy, Kathleen L.
通讯作者：
McCoy, Kathleen L.
影响因子：
64.8
作者：
Graves, Austin R.;Curran, Patricia K.;Mindell, Joseph A.
通讯作者：
Mindell, Joseph A.