title: Lipid rafts and functional caveolae regulate HIV-induced amyloid beta accumulation in brain endothelial cells.
abstract: Amyloid beta (Aβ) levels are increased in HIV-1 infected brains due to not yet fully understood mechanisms. In the present study, we investigate the role of lipid rafts, functional caveolae, and caveolae-associated signaling in HIV-1-induced Aβ accumulation in HBMEC. Both silencing of caveolin-1 (cav-1) and disruption of lipid rafts by pretreatment with beta-methyl-cyclodextrin (MCD) protected against Aβ accumulation in HBMEC. Exposure to HIV-1 and Aβ activated caveolae-associated Ras and p38. While inhibition of Ras by farnesylthiosalicylic acid (FTS) effectively protected against HIV-1-induced accumulation of Aβ, blocking of p38 did not have such an effect. We also evaluated the role of caveolae in HIV-1-induced upregulation of the receptor for advanced glycation end products (RAGE), which regulates Aβ transfer from the blood stream into the central nervous system. HIV-1-induced RAGE expression was prevented by infecting HBMEC with cav-1 specific shRNA lentiviral particles or by pretreatment of cells with FTS. Overall, the present results indicate that Aβ accumulation in HBMEC is lipid raft and caveolae dependent and involves the caveolae-associated Ras signaling.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33136-1019, USA. IAndras@med.miami.edu
authors.forename: Ibolya E
authors.initials: IE
authors.lastname: András
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Eum
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000821:virology; D021941:Caveolae / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005204:Farnesol / Q000031:analogs & derivatives / Q000494:pharmacology; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D018631:ras Proteins