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.


CONCLUSIONS
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.
Pollicita
Michela
M
Department of Experimental Medicine and Biochemical Sciences, University Tor Vergata, Rome, Italy. michela.pollicita@uniroma2.it
Muscoli
Carolina
C
Sgura
Antonella
A
Biasin
Alberto
A
Granato
Teresa
T
Masuelli
Laura
L
Mollace
Vincenzo
V
Tanzarella
Caterina
C
Del Duca
Claudio
C
Rodinò
Paola
P
Perno
Carlo Federico
CF
Aquaro
Stefano
S
D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001254:Astrocytoma / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016615:Telomere / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
D000998:Antiviral Agents; D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine