HIV-1 Transactivator Protein Induces ZO-1 and Neprilysin Dysfunction in Brain Endothelial Cells via the Ras Signaling Pathway. (2nd May 2017)

• Record Type: Journal Article
• Authors: Jiang, Wenlin; Huang, Wen; Chen, Yanlan; Zou, Min; Peng, Dingyue; Chen, Debing
• Other Names: Giudetti Anna M. Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2017(2017)
• Publication Date: 2017-05-02
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2017/3160360
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Amyloid beta (A β ) 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 A β accumulation in human cerebral microvascular endothelial cells (HBEC-5i). Cell viability assay showed that 1 μ g/mL Tat and 20 μ mol/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 A β -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 A β 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 A β deposition in HBEC-5i cells. FTS partially protects blood-brain barrier (BBB) integrity and inhibits A β accumulation.