Functional expression of choline transporter like-protein 1 (CTL1) and CTL2 in human brain microvascular endothelial cells

被引：41

作者：

Iwao, Beniko ^{[1
]}

Yara, Miki ^{[2
]}

Hara, Naomi ^{[2
]}

Kawai, Yuiko ^{[3
]}

Yamanaka, Tsuyoshi ^{[4
]}

Nishihara, Hiroshi ^{[5
]}

Inoue, Takeshi ^{[1
]}

Inazu, Masato ^{[3
,4
]}

机构：

[1] Tokyo Med Univ, Dept Psychiat, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[2] Tokyo Med Univ, Dept Anesthesiol, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[3] Tokyo Med Univ, Inst Med Sci, Shinjuku Ku, 6-1-1 Shinjuku, Tokyo 1608402, Japan

[4] Tokyo Med Univ, Dept Mol Prevent Med, Shinjuku Ku, 6-1-1 Shinjuku, Tokyo 1608402, Japan

[5] Hokkaido Univ, Dept Translat Pathol, Grad Sch Med, Kita Ku, N15 W7, Sapporo, Hokkaido 0608638, Japan

来源：

NEUROCHEMISTRY INTERNATIONAL | 2016年 / 93卷

关键词：

Choline; Transporter; Choline transporter-like protein; Blood-brain barrier; Brain microvascular endothelial cells; ORGANIC CATION TRANSPORTERS; CANCER-THERAPY; RAT-BRAIN; NEURONS; BARRIER; SYSTEM; FAMILY; TARGET; IDENTIFICATION; DRUGS;

D O I：

10.1016/j.neuint.2015.12.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this study, we examined the molecular and functional characterization of choline transporter in human brain microvascular endothelial cells (hBMECs). Choline uptake into hBMECs was a saturable process that was mediated by a Na+-independent, membrane potential and pH-dependent transport system. The cells have two different [H-3]choline transport systems with K-m values of 35.0 +/- 4.9 mu M and 54.1 +/- 8.1 mu M, respectively. Choline uptake was inhibited by choline, acetylcholine (ACh) and the choline analog hemicholinium-3 (HC-3). Various organic cations also interacted with the choline transport system. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed, while mRNA for high-affinity choline transporter 1 (CHT1) and organic cation transporters (OCTs) were not expressed in hBMECs. CTL1 and CTL2 proteins were localized to brain microvascular endothelial cells in human brain cortical sections. Both CTL1 and CTL2 proteins were expressed on the plasma membrane and mitochondria. CTL1 and CTL2 proteins are mainly expressed in plasma membrane and mitochondria, respectively. We conclude that choline is mainly transported via an intermediate-affinity choline transport system, CTL1 and CTL2, in hBMECs. These transporters are responsible for the uptake of extracellular choline and organic cations. CTL2 participate in choline transport mainly in mitochondria, and may be the major site for the control of choline oxidation. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：40 / 50

页数：11

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