HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway

Oxid Med Cell Longev. 2016:2016:4196572. doi: 10.1155/2016/4196572. Epub 2016 Aug 2.

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.

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Brain / cytology*
  • Cell Survival / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • HIV-1 / metabolism*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Occludin / metabolism*
  • Signal Transduction* / drug effects
  • rho GTP-Binding Proteins / metabolism
  • rho-Associated Kinases / metabolism
  • tat Gene Products, Human Immunodeficiency Virus / pharmacology*

Substances

  • Antigens, Neoplasm
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Occludin
  • tat Gene Products, Human Immunodeficiency Virus
  • rho-Associated Kinases
  • MOK protein, human
  • Mitogen-Activated Protein Kinases
  • rho GTP-Binding Proteins