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

I. Cohen, P. Boya, L. Zhao, D. Métivier, K. Andreau, J. L. Perfettini, J. G. Weaver, Andrew David Badley, E. W. Taylor, G. Kroemer

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-192
Number of pages12
JournalApoptosis
Volume9
Issue number2
DOIs
StatePublished - Mar 2004

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Keywords

  • Glutathione
  • Mitochondria
  • Selenium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Cohen, I., Boya, P., Zhao, L., Métivier, D., Andreau, K., Perfettini, J. L., Weaver, J. G., Badley, A. D., Taylor, E. W., & Kroemer, G. (2004). Anti-apoptotic activity of the glutathione peroxidase homologue encoded by HIV-1. Apoptosis, 9(2), 181-192. https://doi.org/10.1023/B:APPT.0000018800.87358.ba