Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels

The blood–brain barrier (BBB) is mainly formed by brain capillary endothelial cells (BCECs) and is exposed to hypoxic environments under pathological conditions. The effects of hypoxia on the expression and activity of Ca2+-activated Cl− (ClCa) channels, TMEM16A, were examined in bovine brain endoth...

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Main Authors: Takahisa Suzuki, Yoshiaki Suzuki, Kiyofumi Asai, Yuji Imaizumi, Hisao Yamamura
Format: Article
Language:English
Published: Elsevier 2021-05-01
Series:Journal of Pharmacological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861321000220
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spelling doaj-4968c6615d40456fad391e34b64d3d942021-04-14T04:15:09ZengElsevierJournal of Pharmacological Sciences1347-86132021-05-0114616569Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channelsTakahisa Suzuki0Yoshiaki Suzuki1Kiyofumi Asai2Yuji Imaizumi3Hisao Yamamura4Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya 467-8603, JapanDepartment of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya 467-8603, JapanDepartment of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi Mizuhocho Mizuhoku, Nagoya 467-8601, JapanDepartment of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya 467-8603, JapanDepartment of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya 467-8603, Japan; Corresponding author. Fax: +81 52 836 3431.The blood–brain barrier (BBB) is mainly formed by brain capillary endothelial cells (BCECs) and is exposed to hypoxic environments under pathological conditions. The effects of hypoxia on the expression and activity of Ca2+-activated Cl− (ClCa) channels, TMEM16A, were examined in bovine brain endothelial t-BBEC117 cells and mouse BCECs. The expression of TMEM16A was upregulated by hypoxia. Whole-cell ClCa currents increased under hypoxia. Hypoxia also increased cell proliferation and trans-endothelial permeability, which were attenuated by ClCa channel blockers or TMEM16A siRNA. These findings are useful for elucidating the pathological role of TMEM16A ClCa channels in the BBB during cerebral ischemia.http://www.sciencedirect.com/science/article/pii/S1347861321000220Brain capillary endothelial cellHypoxiaTMEM16A
collection DOAJ
language English
format Article
sources DOAJ
author Takahisa Suzuki
Yoshiaki Suzuki
Kiyofumi Asai
Yuji Imaizumi
Hisao Yamamura
spellingShingle Takahisa Suzuki
Yoshiaki Suzuki
Kiyofumi Asai
Yuji Imaizumi
Hisao Yamamura
Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels
Journal of Pharmacological Sciences
Brain capillary endothelial cell
Hypoxia
TMEM16A
author_facet Takahisa Suzuki
Yoshiaki Suzuki
Kiyofumi Asai
Yuji Imaizumi
Hisao Yamamura
author_sort Takahisa Suzuki
title Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels
title_short Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels
title_full Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels
title_fullStr Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels
title_full_unstemmed Hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of TMEM16A Ca2+-activated Cl− channels
title_sort hypoxia increases the proliferation of brain capillary endothelial cells via upregulation of tmem16a ca2+-activated cl− channels
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2021-05-01
description The blood–brain barrier (BBB) is mainly formed by brain capillary endothelial cells (BCECs) and is exposed to hypoxic environments under pathological conditions. The effects of hypoxia on the expression and activity of Ca2+-activated Cl− (ClCa) channels, TMEM16A, were examined in bovine brain endothelial t-BBEC117 cells and mouse BCECs. The expression of TMEM16A was upregulated by hypoxia. Whole-cell ClCa currents increased under hypoxia. Hypoxia also increased cell proliferation and trans-endothelial permeability, which were attenuated by ClCa channel blockers or TMEM16A siRNA. These findings are useful for elucidating the pathological role of TMEM16A ClCa channels in the BBB during cerebral ischemia.
topic Brain capillary endothelial cell
Hypoxia
TMEM16A
url http://www.sciencedirect.com/science/article/pii/S1347861321000220
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