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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 3160360, 10 pages
https://doi.org/10.1155/2017/3160360
Research Article

HIV-1 Transactivator Protein Induces ZO-1 and Neprilysin Dysfunction in Brain Endothelial Cells via the Ras Signaling Pathway

1Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China
2Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541000, China

Correspondence should be addressed to Wen Huang; moc.361@9221newh

Received 29 November 2016; Revised 9 February 2017; Accepted 1 March 2017; Published 2 May 2017

Academic Editor: Anna M. Giudetti

Copyright © 2017 Wenlin Jiang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Amyloid beta (Aβ) deposition is increased in human immunodeficiency virus-1- (HIV-1-) infected brain, but the mechanisms are not fully understood. The aim of the present study was to evaluate the role of Ras signaling in HIV-1 transactivator protein- (Tat-) induced Aβ accumulation in human cerebral microvascular endothelial cells (HBEC-5i). Cell viability assay showed that 1 μg/mL Tat and 20 μmol/L of the Ras inhibitor farnesylthiosalicylic acid (FTS) had no significant effect on HBEC-5i cell viability after 24 h exposure. Exposure to Tat decreased protein and mRNA levels of zonula occludens- (ZO-) 1 and Aβ-degrading enzyme neprilysin (NEP) in HBEC-5i cells as determined by western blotting and quantitative real-time polymerase chain reaction. Exposure to Tat also increased transendothelial transfer of Aβ and intracellular reactive oxygen species (ROS) levels; however, these effects were attenuated by FTS. Collectively, these results suggest that the Ras signaling pathway is involved in HIV-1 Tat-induced changes in ZO-1 and NEP, as well as Aβ deposition in HBEC-5i cells. FTS partially protects blood-brain barrier (BBB) integrity and inhibits Aβ accumulation.