Neurodegenerative Effects of Recombinant HIV-1 Tat(1-86) are Associated with Inhibition of Microtubule Formation and Oxidative Stress-Related Reductions in Microtubule-Associated Protein-2(a,b)

作者：Butler Tracy R; Smith Katherine J; Self Rachel L; Braden Brittany B; Prendergast Mark A^*

来源：Neurochemical Research, 2011, 36(5): 819-828.

DOI：10.1007/s11064-011-0409-2

• Acquired immune deficiency syndrome
• Neurotoxicity
• Trolox
• Tubulin

The human immunodeficiency virus 1 (HIV-1) protein Trans-activator of Transcription (Tat) is a nuclear regulatory protein that may contribute to the development of HIV-1 associated dementia by disrupting the neuronal cytoskeleton. The present studies examined effects of recombinant Tat(1-86; 1-100 nM) on microtubule-associated protein (MAP)-dependent and MAP-independent microtubule formation ex vivo and oxidative neuronal injury in rat organotypic hippocampal explants. Acute exposure to Tat(1-86) (a parts per thousand yen1 nM) markedly reduced MAP-dependent and -independent microtubule formation ex vivo, as did vincristine sulfate (0.1-10 mu M). Cytotoxicity, as measured by propidium iodide uptake, was observed in granule cells of the DG with exposure to 100 nM Tat(1-86) for 24 or 72 h, while significant reductions in MAP-2 immunoreactivity were observed in granule cells and pyramidal cells of the CA1 and CA3 regions at each timepoint. These effects were prevented by co-exposure to the soluble vitamin E analog Trolox (500 mu M). Thus, effects of Tat(1-86) on the neuronal viability may be associated with direct interactions with microtubules and generation of oxidative stress.

• 出版日期2011-5