title: Combined effect of 3-aminobenzamide and N-acetylcysteine on HIV replication in chronically infected U937 cells.
abstract: The existence of a close relationship between apoptosis associated with oxidative stress and the increase of viral progeny in chronically HIV-infected cells has been previously reported. The possibility of modulating both phenomena by using an antioxidant such as N-acetylcysteine (NAC) has also been demonstrated. The present investigation was designed to study the role of the nuclear enzyme poly-(ADP-ribose)-polymerase (PARP) when HIV- infected cells are treated with tumour necrosis factor alpha (TNFα), a cytokine capable of inducing both apoptosis and intracellular oxygen free radical production. PARP overexpression may result in a rapid drop of intracellular NAD(+) and ATP concentration, thus contributing to cellular redox imbalance. We have used the specific PARP inhibitor 3- aminobenzamide (3-ABA), alone or in a combination with NAC. 3-ABA was only partially capable of inhibiting viral replication and apoptosis induced by TNFα. In contrast, the combination of NAC and 3-ABA led to an inhibition of apoptosis as well as to a marked decrease in viral particle production, with a parallel replenishment of intracellular reduced glutathione content. The results reported here confirm the potential role of antioxidant drug treatment in specific phases of HIV infection.
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: E
authors.initials: E
authors.lastname: Straface
authors.affiliation: a Department of Ultrastructures , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Giammarioli
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: W
authors.initials: W
authors.lastname: Malorni