The keys of oxidative stress in acquired immune deficiency syndrome apoptosis.
Apoptosis is the main cause of CD4+ T-lymphocyte depletion in acquired immune deficiency syndrome (AIDS). Various agents appear to be able to trigger apoptosis in CD4+ T cells, including viral proteins (i.e. gp120, Tat), inappropriate secretion of inflammatory cytokines by activated macrophages (i.e. tumor necrosis factor alpha) and toxins produced by opportunistic micro-organisms. Since oxidative stress can also induce apoptosis, it can be hypothesized that such a mechanism could participate in CD4+ T-cell apoptosis observed in AIDS. This correlates strongly with the observation that AIDS patients present low levels of antioxidants (i.e. superoxide dismutase-Mn, vitamin E, selenium and glutathion) most likely due to inappropriate nutrition (i.e. diets poor in antioxidants), alcohol and drug consumption, and digestive problems associated with the disease. Furthermore, the coadministration of the antiviral drug zidovudine with antioxidants increases its therapeutic potential. Finally, the following additional observations support the hypothesis that oxidative stress is involved in cell apoptosis in AIDS: (1) The depletion of the anti-apoptotic/antioxidant protein Bcl-2 in human immunodeficiency virus (HIV)-infected CD4+ cells; (2) a decrease of apoptosis in HIV-infected cells treated with antioxidants and; (3) the presence of the pro-apoptotic/pro-oxidant cytokines secreted by activated macrophages in AIDS patients. Therefore, anti-apoptotic/antioxidant strategies should be considered, alongside antiviral strategies, in order to design a more efficient therapy for AIDS in the near future.
Romero-Alvira
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Servicio de Cardiología, Residencia General de la Seguridad Social, Hospital Miguel Servet, Zaragoza, Spain.
Roche
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D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D018384:Oxidative Stress
D000975:Antioxidants