Mass spectrometry-based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin.

Mass spectrometry-based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin.
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DOI:
10.1002/1873-3468.13982
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发表时间:
2020-12
期刊:
影响因子:
3.5
通讯作者:
Barber J
Barber J
中科院分区:
生物学3区
文献类型:
--
作者:
Al-Majdoub ZM;Achour B;Couto N;Howard M;Elmorsi Y;Scotcher D;Alrubia S;El-Khateeb E;Vasilogianni AM;Alohali N;Neuhoff S;Schmitt L;Rostami-Hodjegan A;Barber J

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ABC转运蛋白(ATP结合盒转运蛋白)将药物及其代谢产物转运穿过细胞膜,使ABC转运蛋白表达水平成为调节不同组织和个体中局部药物浓度的关键因素。然而,ABC转运蛋白的定量仍然具有挑战性,因为它们是大而低丰度的跨膜蛋白。在这里,我们通过无标记定量质谱法分析了200份来自人类肝脏、肾脏、肠、脑微血管和皮肤的粗品和膜富集组分样品。我们确定了32个(48个)ABC转运蛋白:ABCD 3在肝脏中最丰富,而ABCA 8,ABCB 2/TAP 1和ABCE 1在所有组织中检测到。有趣的是,该图谱揭示了ABCB 2/TAP 1可能在大脑中具有TAP 2独立的功能,并且胆道闭锁(BA)和对照肝脏具有完全不同的ABC转运蛋白谱。我们建议,有意义的生物信息可以从这些数据集的直接比较。
ABC transporters (ATP‐binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low‐abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane‐enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by label‐free quantitative mass spectrometry. We identified 32 (out of 48) ABC transporters: ABCD3 was the most abundant in liver, whereas ABCA8, ABCB2/TAP1 and ABCE1 were detected in all tissues. Interestingly, this atlas unveiled that ABCB2/TAP1 may have TAP2‐independent functions in the brain and that biliary atresia (BA) and control livers have quite different ABC transporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these data sets.
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