Specificity of ABCA7-mediated cell lipid efflux.
Specificity of ABCA7-mediated cell lipid efflux.
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ABCA 7介导的细胞脂质流出的特异性。
DOI：
10.1016/j.bbalip.2022.159157
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发表时间：
2022-07
期刊：
影响因子：
--
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中科院分区：
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--
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腺苷三磷酸结合盒转运子亚家族A成员7（ABCA 7）执行不完全理解的生化功能，影响阿尔茨海默病的发病机制。ABCA 7在一级结构上与ABCA 1最相似，ABCA 1是介导细胞脂质流出和高密度脂蛋白（HDL）形成的蛋白质。采用脂质代谢标记/示踪剂流出测定来研究BHK-ABCA 7（低表达）、BHK-ABCA 7（高表达）和BHK-ABCA 1细胞中的脂质流出。鸟枪脂质质谱法用于测定由BHK-ABCA 7和BHK-ABCA 1细胞合成的HDL的脂质组成。BHK-ABCA 7（低）细胞表现出显着的流出，只有胆碱磷脂和磷脂酰肌醇。BHK-ABCA 7（高）细胞具有显著的胆固醇和胆碱-磷脂流出至载脂蛋白（apo）A-I、apo E、18 A肽、HDL、血浆和脑脊液，以及鞘氨醇-脂质、丝氨酸-脂质（在BHK细胞中由磷脂酰丝氨酸和磷脂酰乙醇胺组成）和磷脂酰肌醇流出至apo A-I。在apo A-I的外排试验中，调整胆碱磷脂后，ABCA 7介导的外排清除的丝氨酸脂质和磷脂酰肌醇比ABCA 1介导的外排多约4倍，而ABCA 1介导的外排清除的胆固醇比ABCA 7介导的外排多约3倍。鸟枪式脂质组学分析显示，ABCA 7-HDL具有比ABCA 1-HDL少约20 mol%的磷脂酰胆碱和多3-5倍的丝氨酸-脂质和磷脂酰肌醇，而ABCA 1-HDL仅含有比ABCA 7-HDL多约6 mol%（或约1.1倍）的胆固醇。示踪剂流出测定和鸟枪脂质组学之间关于胆固醇的差异可以通过低估ABCA 7介导的胆固醇流出来解释。总体而言，这些结果表明，与ABCA 1相比，ABCA 7缺乏对磷脂酰胆碱的特异性，并且释放的胆固醇显着但并非显着减少。
Adenosine triphosphate-binding cassette transporter subfamily A member 7 (ABCA7) performs incompletely understood biochemical functions that affect pathogenesis of Alzheimer’s disease. ABCA7 is most similar in primary structure to ABCA1, the protein that mediates cell lipid efflux and formation of high-density lipoprotein (HDL). Lipid metabolic labeling/tracer efflux assays were employed to investigate lipid efflux in BHK-ABCA7(low expression), BHK-ABCA7(high expression) and BHK-ABCA1 cells. Shotgun lipid mass spectrometry was used to determine lipid composition of HDL synthesized by BHK-ABCA7 and BHK-ABCA1 cells. BHK-ABCA7(low) cells exhibited significant efflux only of choline-phospholipid and phosphatidylinositol. BHK-ABCA7(high) cells had significant cholesterol and choline-phospholipid efflux to apolipoprotein (apo) A-I, apo E, the 18A peptide, HDL, plasma and cerebrospinal fluid and significant efflux of sphingosine-lipid, serine-lipid (which is composed of phosphatidylserine and phosphatidylethanolamine in BHK cells) and phosphatidylinositol to apo A-I. In efflux assays to apo A-I, after adjustment to choline-phospholipid, ABCA7-mediated efflux removed ~4 times more serine-lipid and phosphatidylinositol than ABCA1-mediated efflux, while ABCA1-mediated efflux removed ~3 times more cholesterol than ABCA7-mediated efflux. Shotgun lipidomic analysis revealed that ABCA7-HDL had ~20 mol% less phosphatidylcholine and 3–5 times more serine-lipid and phosphatidylinositol than ABCA1-HDL, while ABCA1-HDL contained only ~6 mol% (or ~1.1 times) more cholesterol than ABCA7-HDL. The discrepancy between the tracer efflux assays and shotgun lipidomics with respect to cholesterol may be explained by an underestimate of ABCA7-mediated cholesterol efflux in the former approach. Overall, these results suggest that ABCA7 lacks specificity for phosphatidylcholine and releases significantly but not dramatically less cholesterol in comparison with ABCA1.
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影响因子：
4.8
作者：
Landry, Yves D.;Denis, Maxime;Zha, Xiaohui
通讯作者：
Zha, Xiaohui
影响因子：
6.5
作者：
Abe-Dohmae, Sumiko;Kato, Koichi H.;Yokoyama, Shinji
通讯作者：
Yokoyama, Shinji
DOI：
10.1212/nxg.0000000000000079
发表时间：
2016-06
期刊：
Neurology. Genetics
影响因子：
--
作者：
Cukier HN;Kunkle BW;Vardarajan BN;Rolati S;Hamilton-Nelson KL;Kohli MA;Whitehead PL;Dombroski BA;Van Booven D;Lang R;Dykxhoorn DM;Farrer LA;Cuccaro ML;Vance JM;Gilbert JR;Beecham GW;Martin ER;Carney RM;Mayeux R;Schellenberg GD;Byrd GS;Haines JL;Pericak-Vance MA;Alzheimer's Disease Genetics Consortium
通讯作者：
Alzheimer's Disease Genetics Consortium
DOI：
10.1073/pnas.1309273110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Das, Akash;Goldstein, Joseph L.;Radhakrishnan, Arun
通讯作者：
Radhakrishnan, Arun
影响因子：
3.4
作者：
Hotta, Noriko;Abe-Dohmae, Sumiko;Yokoyama, Shinji
通讯作者：
Yokoyama, Shinji