N-ACETYLCYSTEINE PREVENTS TNF-INDUCED MITOCHONDRIAL DAMAGE, APOPTOSISAND VIRAL PARTICLE-PRODUCTION IN HIV-INFECTED U937 CELLS

It has been hypothesized that reactive oxygen intermediates (ROI) can activate human immunodeficiency virus (HIV) replication and that HIV c an trigger programmed cell death (PCD), In this work, we studied PCD i n U937 cultured cells chronically infected with HIV and exposed to tum or necrosis factor alpha (TNF alpha). This cytokine has been shown to induce apoptosis in some cell types and to produce intracellular free radical species including ROI. In addition, it was also demonstrated t hat HIV-induced PCD observable in U937 infected cells can be favored b y TNF exposure, In one of our recent works, evidence was presented tha t the thiol supplier N-acetylcysteine (NAG) can 'protect', at least pa rtially, HIV-infected cells from PCD and determine a significant decre ase in viral progeny, In the present work, we demonstrate (a) that apo ptosis can be easily induced by TNF only in infected U937 cells and no t in control wild-type cells, (b) that daily treatment of TNF-exposed cells with low concentrations of NAC is able to impair viral progeny f ormation as early as 24 h, (c) that the mitochondrial damage induced b y TNF is counteracted by preexposure to NAG, and (d) that NAC alone ex erts changes in mitochondria which may be responsible for the protecti ve effects exerted by this compound, Because of the radical producing capacity of TNF, these results seem to indicate that the protective ef fects of NAC may be due to the specific antioxidant nature of this sub stance which appears to be capable of impairing both the apoptotic mac hinery and viral replication by an intracellular mechanism involving m itochondrial integrity and function.