Evidence against a role of P-glycoprotein in the clearance of the Alzheimer's disease Aβ1-42 peptides
Evidence against a role of P-glycoprotein in the clearance of the Alzheimer's disease Aβ1-42 peptides
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DOI：
10.1007/s12192-014-0566-8
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发表时间：
2015-05-01
影响因子：
3.8
通讯作者：
Salerno, Milena
中科院分区：
文献类型：
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作者：
Bello, Ivan;Salerno, Milena
有人提出，β-淀粉样肽（Aβ）会导致阿尔茨海默氏病大脑中的神经元变性。神经元水平的肽生成与穿过血脑屏障 (BBB) 的消除之间的不平衡导致肽在大脑内积聚。血脑屏障中具有运输 A β 能力的运输系统的识别和功能表征对于理解 A β 肽从大脑到血液的运输至关重要。在这种情况下，有人提出，在 BBB 内皮细胞中表达的 P-糖蛋白 (P-gp) 在 Aβ 的消除中发挥着作用。然而，几乎没有实验证据支持这一点。因此，本研究的目的是确定 P-gp 是否能够转运 Aβ 肽。我们的结果表明，在过表达 P-gp 的 K562 细胞质膜囊泡中测量的 ATP 酶活性不会因 A beta(42) 的存在而增加，表明 A beta(42) 不是 P-gp 底物。同样，吡柔比星的 P-gp 也不受 A beta(42) 的影响。此外，P-gp 的过度表达并不能保护细胞免受 A beta(42) 毒性。综上所述，我们的结果支持 A beta(42) 不由 P-gp 转运的结论。
It has been proposed that the amyloid-beta peptides (A beta) cause the neuronal degeneration in the Alzheimer's disease brain. An imbalance between peptide production at the neuronal level and their elimination across the blood-brain-barrier (BBB) results in peptide accumulation inside the brain. The identification and functional characterization of the transport systems in the BBB with the capacity to transport A beta is crucial for the understanding of A beta peptide traffic from the brain to the blood. In this context, it has been suggested that the P-glycoprotein (P-gp), expressed in endothelial cells of the BBB, plays a role in the elimination of A beta. However, there is little, if any, experimental evidence to support this; therefore, the aim of this investigation was to determine whether P-gp is capable of transporting A beta peptides. Our results show that ATPase activity measured in plasma membrane vesicles of K562 cells overexpressing P-gp is not increased by the presence of A beta(42), suggesting that A beta(42) is not a P-gp substrate. Similarly, P-gp of pirarubicin was unaffected by A beta(42). Moreover, the overexpression of P-gp does not protect cells against A beta(42) toxicity. Taken together, our results support the conclusion that A beta(42) is not transported by P-gp.