title: HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway.
abstract: 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.
authors: Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors: Yanlan
authors: Y
authors: Chen
authors: Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors: Wen
authors: 0000-0002-9055-9873
authors: W
authors: Huang
authors: Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors: Wenlin
authors: W
authors: Jiang
authors: Department of Vasculocardiology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors: Xianghong
authors: X
authors: Wu
authors: Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors: Biao
authors: B
authors: Ye
authors: Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors: Xiaoting
authors: X
authors: Zhou
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D062793:Occludin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D062793:Occludin; D054322:tat Gene Products, Human Immunodeficiency Virus; D054460:rho-Associated Kinases; C498978:MOK protein, human; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins