HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway.
HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway.
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HIV-1 Tat 通过 Rho/ROCK 信号通路调节脑内皮细胞中的 Occludin 和 Aβ 转移受体表达
DOI：
10.1155/2016/4196572
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发表时间：
2016
影响因子：
--
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Chen Y;Huang W;Jiang W;Wu X;Ye B;Zhou X
HIV-1反式激活蛋白（达特）在HIV相关的神经认知障碍中起重要作用。本研究的目的是评估在HIV-1相关病理学背景下，人脑微血管内皮细胞（hCMEC/D3）中闭合蛋白和淀粉样β（Aβ）转移受体之间的关系。采用免疫印迹法和免疫荧光染色法检测hCMEC/D3细胞中occludin、晚期糖基化终产物受体（receptor for advanced glycation end products，RECEPTOR）和低密度脂蛋白受体相关蛋白1（low-density lipoprotein receptor related protein 1，LRP 1）的蛋白表达。使用定量实时聚合酶链反应测定occludin、clopidin和LRP 1的mRNA水平。1 µg/mL的HIV-1达特和30 µmol/L的Rho抑制剂羟基法舒地尔（HF）暴露24 h，对hCMEC/D3细胞活力无显著影响。用HIV-1达特蛋白处理降低了occludin和LRP 1的mRNA和蛋白水平，上调了ccludin的表达;然而，HF减弱了这些作用。这些数据表明，Rho/ROCK信号通路参与了hCMEC/D3细胞中HIV-1 Tat介导的occludin、LRP和LRP 1的变化。HF可能通过保护血脑屏障的完整性和Aβ转移受体的表达而产生有益的影响。
HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aβ) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining. The mRNA levels of occludin, RAGE, and LRP1 were measured using quantitative real-time polymerase chain reaction. HIV-1 Tat at 1 µg/mL and the Rho inhibitor hydroxyfasudil (HF) at 30 µmol/L, with 24 h exposure, had no significant effect on hCMEC/D3 cell viability. Treatment with HIV-1 Tat protein decreased mRNA and protein levels of occludin and LRP1 and upregulated the expression of RAGE; however, these effects were attenuated by HF. These data suggest that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-mediated changes in occludin, RAGE, and LRP1 in hCMEC/D3 cells. HF may have a beneficial influence by protecting the integrity of the blood-brain barrier and the expression of Aβ transfer receptors.