The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages

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Abstract
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 of malondialdehyde, 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.
Funding Information
  • Ministry of University and Scientific Research
  • MURST
  • COFIN (2000)
  • Italian National Council for Researc
  • European Found for Regional Development (POP 94/99)
  • AIDS Project
  • ricerca corrente of the italian ministry of health