The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages.
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.
Mollace
Vincenzo
V
Faculty of Pharmacy, University of Catanzaro Magna Graecia, Roccelletta di Borgia, Italy. mollace@libero.it
Salvemini
Daniela
D
Riley
Dennis P
DP
Muscoli
Carolina
C
Iannone
Michelangelo
M
Granato
Teresa
T
Masuelli
Laura
L
Modesti
Andrea
A
Rotiroti
Domenicantonio
D
Nisticó
Robert
R
Bertoli
Ada
A
Perno
Carlo-Federico
CF
Aquaro
Stefano
S
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*
D017077:Culture Media, Conditioned