Functional expression of choline transporter like-protein 1 (CTL1) and CTL2 in human brain microvascular endothelial cells. (February 2016)

• Record Type: Journal Article
• Authors: Iwao, Beniko; Yara, Miki; Hara, Naomi; Kawai, Yuiko; Yamanaka, Tsuyoshi; Nishihara, Hiroshi; Inoue, Takeshi; Inazu, Masato
• Is Part Of: Neurochemistry international. Volume 93(2016)
• Page Start: 40
• Page End: 50
• Publication Date: 2016-02
• Subjects: Choline -- Transporter -- Choline transporter-like protein -- Blood-brain barrier -- Brain microvascular endothelial cells; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2015.12.011
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: 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 [ 3 H]choline transport systems with Km values of 35.0 ± 4.9 μM and 54.1 ± 8.1 μM, 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. Graphical abstract: Highlights: We examined the functional characteristics of choline uptake in human brain microvascular endothelial cells. Choline uptake is mediated by two transport systems. CTL1 and CTL2 are mainly responsible for the uptake of extracellular choline and organic cations. CTL2 mainly participate in choline transport in mitochondria, and may be the major site for the control of choline oxidation.