Effects on P-Glycoprotein Expression after Blood-Brain Barrier Disruption Using Focused Ultrasound and Microbubbles.

Effects on P-Glycoprotein Expression after Blood-Brain Barrier Disruption Using Focused Ultrasound and Microbubbles.
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DOI:
10.1371/journal.pone.0166061
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
McDannold N
McDannold N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Aryal M;Fischer K;Gentile C;Gitto S;Zhang YZ;McDannold N

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许多试图通过脑内皮细胞的管腔膜的血液传播的物质被多种代谢酶作用或被嵌入的外排转运蛋白(例如渗透性糖蛋白(Pgp))主动排回毛细血管腔。这种蛋白质的过表达也与癌细胞的多药耐药性有关。以前的研究表明,聚焦超声(FUS),当与微泡剂结合时,有能力暂时破坏血脑屏障(BBBD)。在这项工作中,我们研究了Pgp表达的调制是否是FUS诱导效应的一部分。我们发现,超声可以暂时抑制Pgp表达。当在0.55 MPa下产生BBBD时,Pgp被抑制长达48小时,并在72小时内恢复。在0.81 MPa下,抑制可以持续72小时或更长时间。这些发现支持了微泡增强的FUS通过抑制药物外排破坏血脑屏障功能组分的观点。
Many blood-borne substances attempting to pass through the luminal membrane of brain endothelial cells are acted upon by a variety of metabolizing enzymes or are actively expelled back into the capillary lumen by embedded efflux transporters, such as Permeability-glycoprotein (Pgp). Overexpression of this protein has also been linked to multidrug resistance in cancer cells. Previous studies have shown that focused ultrasound (FUS), when combined with a microbubble agent, has ability to temporarily disrupt blood-brain barrier (BBBD). In this work, we investigated whether modulation of Pgp expression is part of the FUS-induced effects. We found that ultrasound can temporarily suppress Pgp expression. When BBBD was produced at 0.55 MPa, Pgp was suppressed up to 48 hours and restored by 72 hours. At 0.81 MPa, suppression can last 72 hours or longer. These findings support the idea that microbubble-enhanced FUS disrupts the functional components of the BBB through suppression of drug efflux.
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