title: N-acetylcysteine prevents TNF-induced mitochondrial damage, apoptosis and viral particle production in HIV-infected U937 cells.
abstract: It has been hypothesized that reactive oxygen intermediates (ROI) can activate human immunodeficiency virus (HIV) replication and that HIV can trigger programmed cell death (PCD). In this work, we studied PCD in U937 cultured cells chronically infected with HIV and exposed to tumor necrosis factor alpha (TNFα). 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 that HIV-induced PCD observable in U937 infected cells can be favored by TNF exposure. In one of our recent works, evidence was presented that the thiol supplier N-acetylcysteine (NAC) can 'protect', at least partially, HIV-infected cells from PCD and determine a significant decrease in viral progeny. In the present work, we demonstrate (a) that apoptosis can be easily induced by TNF only in infected U937 cells and not in control wild-type cells, (b) that daily treatment of TNF-exposed cells with low concentrations of NAC is able to impair viral progeny formation as early as 24 h, (c) that the mitochondrial damage induced by TNF is counteracted by preexposure to NAC, and (d) that NAC alone exerts changes in mitochondria which may be responsible for the protective effects exerted by this compound. Because of the radical producing capacity of TNF, these results seem to indicate that the protective effects of NAC may be due to the specific antioxidant nature of this substance which appears to be capable of impairing both the apoptotic machinery and viral replication by an intracellular mechanism involving mitochondrial integrity and function.
authors.affiliation: a Department of Ultrastructures , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: W
authors.initials: W
authors.lastname: Malorni
authors.affiliation: a Department of Ultrastructures , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rivabene
authors.affiliation: a Department of Ultrastructures , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Santini
authors.affiliation: a Department of Ultrastructures , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rainaldi
authors.affiliation: a Department of Ultrastructures , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Donelli