skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

Abstract

Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell deathmore » in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.« less

Authors:
 [1];  [1];  [2];  [2]; ;  [1];  [3];  [1]
  1. Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)
  2. (Japan)
  3. Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan)
Publication Date:
OSTI Identifier:
22207423
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 411; Journal Issue: 2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BLOOD-BRAIN BARRIER; BRAIN; CALCIUM IONS; CAPILLARIES; CATTLE; CELL PROLIFERATION; ENDOPLASMIC RETICULUM; GENE REGULATION; HOMEOSTASIS; MEMBRANES; RECTIFIERS

Citation Formats

Kito, Hiroaki, Yamazaki, Daiju, Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto, Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Ohya, Susumu, Yamamura, Hisao, Asai, Kiyofumi, and Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp. Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.06.128.
Kito, Hiroaki, Yamazaki, Daiju, Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto, Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Ohya, Susumu, Yamamura, Hisao, Asai, Kiyofumi, & Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp. Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells. United States. doi:10.1016/J.BBRC.2011.06.128.
Kito, Hiroaki, Yamazaki, Daiju, Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto, Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Ohya, Susumu, Yamamura, Hisao, Asai, Kiyofumi, and Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp. Fri . "Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells". United States. doi:10.1016/J.BBRC.2011.06.128.
@article{osti_22207423,
title = {Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells},
author = {Kito, Hiroaki and Yamazaki, Daiju and Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto and Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya and Ohya, Susumu and Yamamura, Hisao and Asai, Kiyofumi and Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp},
abstractNote = {Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.},
doi = {10.1016/J.BBRC.2011.06.128},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 411,
place = {United States},
year = {2011},
month = {7}
}