Role of ATP synthase alpha subunit in low-dose endothelial monocyte-activating polypeptide-II-induced opening of the blood-tumor barrier
Role of ATP synthase alpha subunit in low-dose endothelial monocyte-activating polypeptide-II-induced opening of the blood-tumor barrier
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ATP合酶α亚基在低剂量内皮单核细胞激活多肽-II诱导的血肿瘤屏障开放中的作用
DOI：
10.1016/j.jns.2010.09.034
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发表时间：
2011-01-15
影响因子：
4.4
通讯作者：
Liu, Li-bo
中科院分区：
文献类型：
--
作者：
Li, Zhen;Liu, Yun-hui;Liu, Li-bo
本研究旨在确定脑微血管内皮细胞（BMEC）上ATP合酶（α-ATP合酶）的α亚基是否作为内皮单核细胞激活多肽-II（EMAP-II）诱导的血肿瘤屏障（BIB）通透性增加的功能靶点。使用大鼠CO胶质瘤模型，我们发现低剂量（80 ng/kg）EMAP-11显著降低BMEC上紧密连接（TJ）相关蛋白claudin-5、occludin和ZO-1的mRNA和蛋白表达水平。同时放射免疫和Western blot检测显示肿瘤组织cAMP和蛋白激酶A催化亚单位（PKAcs）的表达水平明显降低。此外，用特异性α-ATP合酶抗体预处理显著阻断EMAP-II对TJ相关蛋白、cAMP和PKAcs的作用。此外，免疫荧光双标法证实EMAP-Ⅱ与α-ATP合酶共定位于BMEC上。本研究表明BMEC上ATP合酶的一个亚基是EMAP-Ⅱ选择性开放BTB的功能靶点，cAMP/PKA信号转导通路可能参与了这一调节过程。(c)2010 Elsevier B. V.保留所有权利。
This study was performed to determine whether the a subunit of ATP synthase (alpha-ATP synthase) on brain microvascular endothelial cells (BMECs) serves as the functional target for endothelial monocyte-activating polypeptide-II (EMAP-II)-induced increase in blood-tumor barrier (BIB) permeability. Using a rat CO glioma model, we found that low-dose (80 ng/kg) EMAP-Il significantly decreased the mRNA and protein expression levels of tight junction (TJ)-related proteins claudin-5, occludin, and ZO-1 on BMECs. Meantime. radioimmunity and Western blot assay she-red a significant decrease in the expression levels of cAMP and catalytic subunit of protein kinase A (PKAcs) of tumor tissues. Also, pretreatment with specific a-ATP synthase antibody significantly blocked the effects of EMAP-II on TJ-related proteins, cAMP, and PKAcs. In addition, double immunofluorescence assay identified that EMAP-II was co-localized with a-ATP synthase on BMECs. This in vivo study demonstrated that a subunit of ATP synthase on BMECs serves as the functional target for EMAP-Il selective opening of the BTB, and that cAMP/PKA signaling transduction pathway might be involved in the modulating process. (c) 2010 Elsevier B.V. All rights reserved.