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 patientsundergoing AIDS dementia complex. We demonstrated that supernatantsfrom human primary macrophages (M/M) infected by HIV‐1 lead humanastroglial cells to oxidative stress, as shown by elevated levels ofmalondialdehyde, and then to apoptosis. Electron microscopy ofastrocytes shortly incubated with HIV‐1‐infected M/M supernatantsshowed apoptotic blebbing, cytoplasmic loss, and chromatincondensation. Apoptosis was antagonized by pretreating astrocytes withthe nonpeptidic superoxide dismutase (SOD) mimetic M40401 but notwith anti‐HIV‐1 compounds, thus showing that apoptosis of astrocytesdriven by HIV‐1‐infected M/M supernatants is mainly mediated byabnormal production of superoxide anions without relationship to HIV‐1replication in such cells. Overall results support the role ofoxidative stress mediated by HIV‐1‐infected M/M as one of the leadingcauses of neurodegeneration in patients with HIV‐1 and suggest the useof nonpeptidic SOD mimetics to counteract HIV‐1‐related neurologicaldisorders.