Involvement of Choline Transporter-Like Proteins, CTL1 and CTL2, in Glucocorticoid-Induced Acceleration of Phosphatidylcholine Synthesis via Increased Choline Uptake
Involvement of Choline Transporter-Like Proteins, CTL1 and CTL2, in Glucocorticoid-Induced Acceleration of Phosphatidylcholine Synthesis via Increased Choline Uptake
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DOI：
10.1248/bpb.33.691
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发表时间：
2010-04-01
影响因子：
2
通讯作者：
Tamai, Ikumi
中科院分区：
文献类型：
--
作者：
Nakamura, Toshimichi;Fujiwara, Ryohei;Tamai, Ikumi
磷脂酰胆碱（PC）的产生被糖皮质激素（例如地塞米松（DEX））加速，糖皮质激素增强胎儿肺成熟，促进肺泡II型（ATII）细胞的分化，并增加肺表面活性物质的脂质和蛋白质组分的产生。我们以前证明，抑制ATII细胞的胆碱摄取导致PC合成减少。由于胆碱摄取可能在正常呼吸的PC产生和肺表面活性物质稳态中起关键作用，因此感兴趣的是表征ATII细胞中控制胆碱处置的转运蛋白。因此，我们研究了胆碱转运蛋白在A549细胞，一个人ATII细胞系的基因调控和活性。将A549细胞暴露于DEX 24 h，并使用实时逆转录聚合酶链反应测量胆碱转运体样蛋白1（CTL 1）和CTL 2的mRNA表达水平。DEX处理A549细胞强烈诱导CTL 1和CTL 2 mRNA，并且DEX处理的细胞显示[H-3]胆碱的初始摄取率显着增加，在ATP耗尽的条件下评估了这一点，以阻断胆碱消耗的影响。通过胆碱激酶。转染A549细胞的CTL 1-或CTL 2-小干扰RNA显着降低[H-3]胆碱摄取。总之，A549细胞中的胆碱转运通过DEX处理而增加，并且这种增加是通过诱导功能性胆碱转运蛋白CTL 1和CTL 2介导的。
Phosphatidylcholine (PC) production is accelerated by glucocorticoid, such as dexamethasone (DEX), which enhances fetal lung maturation, promotes differentiation of alveolar type II (ATII) cells, and increases production of both lipid and protein components of lung surfactant. We previously demonstrated that inhibition of choline uptake by ATII cells leads to a decrease of PC synthesis. Since choline uptake may play a critical role in PC production and lung surfactant homeostasis for normal breathing, it is of interest to characterize transporters controlling the disposition of choline in ATII cells. Therefore, we studied the gene regulation and activity of choline transporters in A549 cells, a human ATII cell line. A549 cells were exposed to DEX for 24 h, and mRNA expression levels of choline transporters-like protein 1, (CTL1) and CTL2, were measured using real-time reverse transcription polymerase chain reaction. CTL1 and CTL2 mRNAs were strongly induced by DEX treatment of A549 cells, and the DEX-treated cells showed a significant increase in initial uptake rate of [H-3]choline, which was assessed under ATP-depleted conditions to block the influence of consumption of choline by choline kinase. Transfection of A549 cells with either CTL1- or CTL2-small interfering RNAs significantly decreased [H-3]choline uptake. In conclusion, choline transport in A549 cells is increased by treatment with DEX, and the increase is mediated by induction of functional choline transporters CTL1 and CTL2.