TY - JOUR
T1 - 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)
AU - Butler, Tracy R.
AU - Smith, Katherine J.
AU - Self, Rachel L.
AU - Braden, Brittany B.
AU - Prendergast, Mark A.
PY - 2011/5
Y1 - 2011/5
N2 - 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) (a1 nM) markedly reduced MAP-dependent and -independent microtubule formation ex vivo, as did vincristine sulfate (0.1-10 μM). 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 μM). Thus, effects of Tat(1-86) on the neuronal viability may be associated with direct interactions with microtubules and generation of oxidative stress.
AB - 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) (a1 nM) markedly reduced MAP-dependent and -independent microtubule formation ex vivo, as did vincristine sulfate (0.1-10 μM). 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 μM). Thus, effects of Tat(1-86) on the neuronal viability may be associated with direct interactions with microtubules and generation of oxidative stress.
KW - Acquired immune deficiency syndrome
KW - Neurotoxicity
KW - Trolox
KW - Tubulin
UR - http://www.scopus.com/inward/record.url?scp=79954448574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954448574&partnerID=8YFLogxK
U2 - 10.1007/s11064-011-0409-2
DO - 10.1007/s11064-011-0409-2
M3 - Article
C2 - 21259049
AN - SCOPUS:79954448574
SN - 0364-3190
VL - 36
SP - 819
EP - 828
JO - Neurochemical Research
JF - Neurochemical Research
IS - 5
ER -