Email updates

Keep up to date with the latest news and content from BMC Neuroscience and BioMed Central.

Open Access Research article

Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line

Michela Pollicita1*, Carolina Muscoli234, Antonella Sgura5, Alberto Biasin5, Teresa Granato6, Laura Masuelli7, Vincenzo Mollace28, Caterina Tanzarella5, Claudio Del Duca9, Paola Rodinò6, Carlo Federico Perno1 and Stefano Aquaro110

Author Affiliations

1 Department of Experimental Medicine and Biochemical Sciences, University Tor Vergata, Rome, Italy

2 Faculty of Pharmacy, University Magna Graecia, Catanzaro, Italy

3 IRCCS, San Raffaele La Pisana, Rome, Italy

4 Pharmaceutical Biotecnogical Center, University Tor Vergata, Rome, Italy

5 Department Biology, University Roma3, Rome, Italy

6 Institute of Molecular Biology and Pathology IBPM-CNR, Rome, Italy

7 Department of Experimental Medicine, University Sapienza, Rome, Italy

8 CETA, ARPACal, Catanzaro, Italy

9 Department of Biology, University Tor Vergata, Rome, Italy

10 Department of Pharmaco-Biology, University of Calabria, Rende, Italy

For all author emails, please log on.

BMC Neuroscience 2009, 10:51  doi:10.1186/1471-2202-10-51

Published: 22 May 2009

Abstract

Background

Oxidative stress plays a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV-1) infection causing apoptosis of astroglia cells and neurons. Recent data have shown that oxidative stress is also responsible for the acceleration of human fibroblast telomere shortening in vitro. In the present study we analyzed the potential relations occurring between free radicals formation and telomere length during HIV-1 mediated astroglial death.

Results

To this end, U373 human astrocytoma cells have been directly exposed to X4-using HIV-1IIIB strain, for 1, 3 or 5 days and treated (where requested) with N-acetylcysteine (NAC), a cysteine donor involved in the synthesis of glutathione (GSH, a cellular antioxidant) and apoptosis has been evaluated by FACS analysis. Quantitative-FISH (Q-FISH) has been employed for studying the telomere length while intracellular reduced/oxidized glutathione (GSH/GSSG) ratio has been determined by High-Performance Liquid Chromatography (HPLC). Incubation of U373 with HIV-1IIIB led to significant induction of cellular apoptosis that was reduced in the presence of 1 mM NAC. Moreover, NAC improved the GSH/GSSG, a sensitive indicator of oxidative stress, that significantly decreased after HIV-1IIIB exposure in U373. Analysis of telomere length in HIV-1 exposed U373 showed a statistically significant telomere shortening, that was completely reverted in NAC-treated U373.

Conclusion

Our results support the role of HIV-1-mediated oxidative stress in astrocytic death and the importance of antioxidant compounds in preventing these cellular damages. Moreover, these data indicate that the telomere structure, target for oxidative damage, could be the key sensor of cell apoptosis induced by oxidative stress after HIV infection.