Open AccessA Helical Polypeptide‐Based Potassium Ionophore Induces Endoplasmic Reticulum Stress‐Mediated Apoptosis by Perturbing Ion Homeostasis
Author(s) -
Lee DaeYong,
Lee SooHwan,
Noh Ilkoo,
Oh Eonju,
Ryu Hyunil,
Ha JongHoon,
Jeong SeongDong,
Yoo Jisang,
Jeon TaeJoon,
Yun ChaeOk,
Kim YeuChun
Publication year - 2019
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201801995
Subject(s) - endoplasmic reticulum , homeostasis , unfolded protein response , apoptosis , microbiology and biotechnology , programmed cell death , chemistry , potassium , mitochondrion , biophysics , biochemistry , biology , organic chemistry
Perturbation of potassium homeostasis can affect various cell functions and lead to the onset of programmed cell death. Although ionophores have been intensively used as an ion homeostasis disturber, the mechanisms of cell death are unclear and the bioapplicability is limited. In this study, helical polypeptide‐based potassium ionophores are developed to induce endoplasmic reticulum (ER) stress‐mediated apoptosis. The polypeptide‐based potassium ionophores disturb ion homeostasis and then induce prolonged ER stress in the cells. The ER stress results in oxidative environments that accelerate the activation of mitochondria‐dependent apoptosis. Moreover, ER stress‐mediated apoptosis is triggered in a tumor‐bearing mouse model that suppresses tumor proliferation. This study provides the first evidence showing that helical polypeptide‐based potassium ionophores trigger ER stress‐mediated apoptosis by perturbation of potassium homeostasis.