A Helical Polypeptide-Based Potassium Ionophore Induces Endoplasmic Reticulum Stress-Mediated Apoptosis by Perturbing Ion Homeostasis

Dae Yong Lee, Soo Hwan Lee, Ilkoo Noh, Eonju Oh, Hyunil Ryu, Jong Hoon Ha, Seong Dong Jeong, Jisang Yoo, Tae Joon Jeon, Chae Ok Yun, Yeu Chun Kim

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number1801995
JournalAdvanced Science
Volume6
Issue number14
DOIs
StatePublished - 2019 Jul 17

Fingerprint

Potassium Ionophores
Ionophores
endoplasmic reticulum
homeostasis
Endoplasmic Reticulum Stress
Polypeptides
polypeptides
apoptosis
Cell death
Potassium
potassium
Homeostasis
Ions
Apoptosis
Peptides
ions
Tumors
Cell Death
Bearings (structural)
tumors

Keywords

  • ER stress
  • apoptosis
  • cancer therapy
  • perturbed potassium homeostasis
  • potassium ionophore

Cite this

Lee, Dae Yong ; Lee, Soo Hwan ; Noh, Ilkoo ; Oh, Eonju ; Ryu, Hyunil ; Ha, Jong Hoon ; Jeong, Seong Dong ; Yoo, Jisang ; Jeon, Tae Joon ; Yun, Chae Ok ; Kim, Yeu Chun. / A Helical Polypeptide-Based Potassium Ionophore Induces Endoplasmic Reticulum Stress-Mediated Apoptosis by Perturbing Ion Homeostasis. In: Advanced Science. 2019 ; Vol. 6, No. 14.
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abstract = "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.",
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A Helical Polypeptide-Based Potassium Ionophore Induces Endoplasmic Reticulum Stress-Mediated Apoptosis by Perturbing Ion Homeostasis. / Lee, Dae Yong; Lee, Soo Hwan; Noh, Ilkoo; Oh, Eonju; Ryu, Hyunil; Ha, Jong Hoon; Jeong, Seong Dong; Yoo, Jisang; Jeon, Tae Joon; Yun, Chae Ok; Kim, Yeu Chun.

In: Advanced Science, Vol. 6, No. 14, 1801995, 17.07.2019.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lee, Soo Hwan

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AU - Oh, Eonju

AU - Ryu, Hyunil

AU - Ha, Jong Hoon

AU - Jeong, Seong Dong

AU - Yoo, Jisang

AU - Jeon, Tae Joon

AU - Yun, Chae Ok

AU - Kim, Yeu Chun

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