title: The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages.
abstract: Apoptosis of neurons and astrocytes has been found in patients undergoing AIDS dementia complex. We demonstrated that supernatants from human primary macrophages (M/M) infected by HIV-1 lead human astroglial cells to oxidative stress, as shown by elevated levels of malondialdehyde, and then to apoptosis. Electron microscopy of astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic blebbing, cytoplasmic loss, and chromatin condensation. Apoptosis was antagonized by pretreating astrocytes with the nonpeptidic superoxide dismutase (SOD) mimetic M40401 but not with anti-HIV-1 compounds, thus showing that apoptosis of astrocytes driven by HIV-1-infected M/M supernatants is mainly mediated by abnormal production of superoxide anions without relationship to HIV-1 replication in such cells. Overall results support the role of oxidative stress mediated by HIV-1-infected M/M as one of the leading causes of neurodegeneration in patients with HIV-1 and suggest the use of nonpeptidic SOD mimetics to counteract HIV-1-related neurological disorders.
authors.affiliation: Faculty of Pharmacy, University of Catanzaro Magna Graecia, Roccelletta di Borgia, Italy. mollace@libero.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.forename: Daniela
authors.initials: D
authors.lastname: Salvemini
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Riley
authors.forename: Carolina
authors.initials: C
authors.lastname: Muscoli
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Iannone
authors.forename: Teresa
authors.initials: T
authors.lastname: Granato
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.forename: Domenicantonio
authors.initials: D
authors.lastname: Rotiroti
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticó
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Stefano
authors.initials: S
authors.lastname: Aquaro
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D017077:Culture Media, Conditioned