ABCA1
丹吉尔病
溶血磷脂酰胆碱
ATP结合盒传送带1
磷脂酰乙醇胺
磷脂酰胆碱
化学
胆固醇
流出
ATP结合盒运输机
生物化学
生物
磷脂
运输机
膜
基因
作者
Maiko Tomioka,Yoshinobu Toda,Noralyn B. Mañucat,Hiroyasu Akatsu,Manabu Fukumoto,Nozomu Kono,Hiroyuki Arai,Noriyuki Kioka,Kazumitsu Ueda
标识
DOI:10.1016/j.bbalip.2017.03.012
摘要
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.
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