STIMULATION OF GLUTATHIONE-PEROXIDASE ACTIVITY DECREASES HIV TYPE-1 ACTIVATION AFTER OXIDATIVE STRESS

Am important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kapp a B) by redox-controlled signal transduction pathways. In this study, we demonstrate that selenium supplementation can effectively increase glutathione peroxidase (GPx) activity in latently infected T lymphocyt es. The Se-supplemented cells exhibited an important protection agains t the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). Concomitantly, NF-kappa B activation by H2O2 was also decreased in Se- supplemented cells. Selenium stimulation of GPx activity also induces a protective effect against cell activation by tumor necrosis factor a lpha (TNF-alpha) but less significantly by phorbol esters such as PMA. These Se-mediated effects were specific because they were not found w hen AP-1 DNA-binding activity was studied after H2O2-induced stress. H yperthermia was also studied because it could promote intracellular el ectron leakage in electron transport chains. Elevating the temperature to 42 degrees C did not induce NF-kappa B directly. Rather, it sensit ized infected cells to subsequent oxidative stress by H2O2, demonstrat ing the importance of hyperthermia, often associated with opportunisti c infections in the development of immunodeficiency. In this case, Se induced partial protection against the sensitizing effect of hyperther mia.