Anti-apoptotic activity of the glutathione peroxidase homologue encoded by HIV-1.

The third reading frame of the envelope gene from HIV-1 codes for a protein homologous to the human selenoprotein glutathione peroxidase (GPX). Cells stably or transiently transfected with a HIV-1 GPX construct are protected against the loss of the mitochondrial transmembrane potential and subsequent cell death induced by exogenous reactive oxygen species (ROS) as well as mitochondrion-generated ROS. However, HIV-1 GPX does not confer a general apoptosis resistance, because HIV-1 GPX-transfected cells were not protected against cell death induced by staurosporine or oligomycin. The inhibition of cell death induced by the ROS donor tert-butylhydroperoxide was also observed in cells depleted from endogenous glutathione (GSH), suggesting that GSH is not the sole electron acceptor for HIV-1 GPX. Clinical HIV-1 isolates from long-term non-progressors (untreated patients with diagnosed HIV-1 infection for > 10 years, with CD4 T cell count of > 500 cells/mm3) mostly possess an intact GPX gene (with only 18% of loss-of-function mutations), while HIV-1 isolates from patients developing AIDS contain non-functional GPX mutants in 9 out of 17 cases (53%). Altogether, these data suggest that HIV-1 GPX possesses a cytoprotective, pathophysiologically relevant function.

Cordyceps sinensis extracts do not prevent Fas-receptor and hydrogen peroxide-induced T-cell apoptosis.

Aqueous and alcohol extracts of Cordyceps sinensis (Berk) Succ. are used as a traditional medicine in China for the treatment of a wide range of diseases and are reported to have antioxidant and antiapoptotic properties. We therefore examined the ability of aqueous, organic, and alcohol extracts of Cordyceps sinensis to inhibit apoptosis induced either by hydrogen peroxide or Fas-receptor ligation; both stimuli induce apoptosis dependent on reactive oxygen species. Cells pre-incubated with Cordyceps sinensis extracts were equally sensitive to hydrogen peroxide and Fas-mediated apoptosis. Thus, the putative antioxidant and antiapoptotic properties of Cordyceps sinensis are insufficient to rescue cells from apoptosis induced by these stimuli in vitro.