Lysophosphatidylcholine export by human ABCA7
Lysophosphatidylcholine export by human ABCA7
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人 ABCA7 输出溶血磷脂酰胆碱
DOI：
10.1016/j.bbalip.2017.03.012
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
and Kazumitsu Ueda
中科院分区：
文献类型：
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作者：
Maiko Tomioka;Yoshinobu Toda;Noralyn B. Manucat;Hiroyasu Akatsu;Manabu Fukumoto;Nozomu Kono;Hiroyuki Arai;Noriyuki Kioka;and Kazumitsu Ueda
ATP 结合盒转运蛋白 A7 (ABCA7) 在大脑中高表达，与阿尔茨海默病 (AD) 的发病机制有关。然而，ABCA7 及其转运底物的生理功能仍不清楚。对 AD 和非 AD 受试者的人脑切片进行的免疫组织化学分析表明，ABCA7 在大脑皮层的神经元和小胶质细胞中表达。在 BHK/ABCA7 细胞中鉴定了转运底物和受体，并与 ABCA1 细胞进行了比较。与 ABCA1 一样，ABCA7 在 apoA-I 和 apoE 存在的情况下输出胆碱磷脂；然而，与 ABCA1 不同的是，胆固醇流出量很小。 ABCA7 的脂质流出被 5 μg/ml apoA-I 饱和，并且不依赖于 apoE 异构体，而 ABCA1 的流出依赖于高达 20 μg/ml 的 apoA-I 和 apoE 异构体。液相色谱-串联质谱分析显示，这两种蛋白质对磷脂输出具有不同的偏好：ABCA7 优先选择磷脂酰胆碱 (PC) ≥ lysoPC > 鞘磷脂 (SM) = 磷脂酰乙醇胺 (PE)，而 ABCA1 优先选择 PC > > SM > PE = lysoPC。 ABCA7 和 ABCA1 之间脂质峰模式的主要差异是 ABCA7 的高 lysoPC/PC 比率。这些结果表明，lysoPC 是 ABCA7 的主要转运底物之一，并且 lysoPC 输出可能是大脑中 ABCA7 的重要生理功能。
The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1. Like ABCA1, ABCA7 exported choline phospholipids in the presence of apoA-I and apoE; however, unlike ABCA1, cholesterol efflux was marginal. Lipid efflux by ABCA7 was saturated by 5 μg/ml apoA-I and was not dependent on apoE isoforms, whereas efflux by ABCA1 was dependent on apoA-I up to 20 μg/ml and apoE isoforms. Liquid chromatography–tandem mass spectrometry analyses revealed that the two proteins had different preferences for phospholipid export: ABCA7 preferred phosphatidylcholine (PC) ≥ lysoPC > sphingomyelin (SM) = phosphatidylethanolamine (PE), whereas ABCA1 preferred PC > > SM > PE = lysoPC. The major difference in the pattern of lipid peaks between ABCA7 and ABCA1 was the high lysoPC/PC ratio of ABCA7. These results suggest that lysoPC is one of the major transport substrates for ABCA7 and that lysoPC export may be a physiologically important function of ABCA7 in the brain.