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