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

Takahisa Suzuki; Yoshiaki Suzuki; Kiyofumi Asai; Yuji Imaizumi; Hisao Yamamura

doi:10.1016/j.jphs.2021.03.002

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

J Pharmacol Sci. 2021 May;146(1):65-69. doi: 10.1016/j.jphs.2021.03.002. Epub 2021 Mar 15.

Authors

Takahisa Suzuki¹, Yoshiaki Suzuki¹, Kiyofumi Asai², Yuji Imaizumi¹, Hisao Yamamura³

Affiliations

¹ Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya 467-8603, Japan.
² Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi Mizuhocho Mizuhoku, Nagoya 467-8601, Japan.
³ Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya 467-8603, Japan. Electronic address: yamamura@phar.nagoya-cu.ac.jp.

PMID: 33858657
DOI: 10.1016/j.jphs.2021.03.002

Abstract

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^- (Cl_Ca) channels, TMEM16A, were examined in bovine brain endothelial t-BBEC117 cells and mouse BCECs. The expression of TMEM16A was upregulated by hypoxia. Whole-cell Cl_Ca currents increased under hypoxia. Hypoxia also increased cell proliferation and trans-endothelial permeability, which were attenuated by Cl_Ca channel blockers or TMEM16A siRNA. These findings are useful for elucidating the pathological role of TMEM16A Cl_Ca channels in the BBB during cerebral ischemia.

Keywords: Brain capillary endothelial cell; Hypoxia; TMEM16A.

MeSH terms

Animals
Anoctamin-1 / genetics*
Anoctamin-1 / metabolism*
Blood-Brain Barrier / cytology*
Blood-Brain Barrier / pathology*
Brain / cytology*
Cattle
Cell Line
Cell Proliferation*
Endothelial Cells / metabolism*
Endothelial Cells / pathology*
Gene Expression / genetics*
Hypoxia-Ischemia, Brain / genetics*
Hypoxia-Ischemia, Brain / pathology*
Mice
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Up-Regulation / genetics*

Substances

ANO1 protein, mouse
Anoctamin-1
RNA, Small Interfering