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(Journal of Leukocyte Biology. 2002;71:65-72.)
© 2002 by Society for Leukocyte Biology

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

Vincenzo Mollace*, Daniela Salvemini{dagger}, Dennis P. Riley{dagger}, Carolina Muscoli*, Michelangelo Iannone{ddagger}, Teresa Granato{ddagger}, Laura Masuelli§, Andrea Modesti§, Domenicantonio Rotiroti*, Robert Nisticó§, Ada Bertoli||, Carlo-Federico Perno§,|| and Stefano Aquaro§

* Faculty of Pharmacy, University of Catanzaro "Magna Graecia", Roccelletta di Borgia, Italy;
{dagger} MetaPhore Pharmaceuticals, St. Louis, Missouri;
{ddagger} IBAF CNR, Roccelletta di Borgia, Catanzaro, Italy;
§ Department of Experimental Medicine and Biochemical Sciences, University of Rome ‘Tor Vergata’, Italy; and
|| IRCCS "L. Spallanzani", Rome, Italy

Correspondence: Vincenzo Mollace, M.D., Faculty of Pharmacy, University of Catanzaro "Magna Graecia", Roccelletta di Borgia, 88100 Catanzaro, Italy. E-mail: mollace{at}libero.it

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.

Key Words: SOD-mimetic • monocytes • reservoirs • therapy • AIDS dementia complex • M40401




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