title: Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human brain microvascular endothelial cells.
abstract: Ethanol may have significant effects on human immunodeficiency virus type I (HIV-1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied on the proapoptotic potential of various HIV-1 proteins in primary isolated human brain microvascular endothelial cells (MVECs), a major cellular component of the blood-brain barrier. Low-passage primary brain MVECs were treated with recombinant HIV-1 proteins Nef, Vpr, Tat and gp120 proteins from X4, R5, and X4R5 viral strains, with and without ethanol at various relevant concentrations. The apoptotic potential of each HIV-1 protein with and without ethanol was compared with cells treated with ethanol alone or GST protein as a control, under similar conditions. Specific HIV-1 proteins induced apoptosis in primary isolated human brain MVECs, which was potentiated on treatment with 0.1 and 0.3% (v/v) ethanol. Cotreatment with ethanol and specific HIV-1 proteins showed enhanced lactate dehydrogenase release, compared with MVECs treated with ethanol alone. The presence of ethanol in in vitro culture medium also enhanced HIV-1 protein-mediated tumor necrosis factor-alpha production, compared with cells treated with ethanol alone or GST protein. Thus, these studies demonstrate ethanol's potential for inducing apoptosis of human MVECs with relevant HIV-1-specific proteins and suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and neuropathogenesis in vivo.
authors.affiliation: The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferdon University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Acheampong
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mukhtar
authors.forename: Zahida
authors.initials: Z
authors.lastname: Parveen
authors.forename: Noel
authors.initials: N
authors.lastname: Ngoubilly
authors.forename: Navid
authors.initials: N
authors.lastname: Ahmad
authors.forename: Charvi
authors.initials: C
authors.lastname: Patel
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D015693:Gene Products, nef / Q000633:toxicity; D015696:Gene Products, tat / Q000633:toxicity; D016336:Gene Products, vpr / Q000633:toxicity; D015699:HIV Envelope Protein gp120 / Q000633:toxicity; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014764:Viral Proteins / Q000633:toxicity*; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D015696:Gene Products, tat; D016336:Gene Products, vpr; D015699:HIV Envelope Protein gp120; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000431:Ethanol; D007770:L-Lactate Dehydrogenase