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)

Tracy R. Butler, Katherine J. Smith, Rachel L. Self, Brittany Braden, Mark A. Prendergast

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)819-828
Number of pages10
JournalNeurochemical Research
Volume36
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

Fingerprint

Oxidative stress
Microtubule-Associated Proteins
Trans-Activators
Transcription
Viruses
Microtubules
HIV-1
Oxidative Stress
Human Immunodeficiency Virus Proteins
Propidium
Pyramidal Cells
Vincristine
Cytotoxicity
Nuclear Proteins
Cytoskeleton
Vitamin E
Dementia
Rats
Proteins
Inhibition (Psychology)

Keywords

  • Acquired immune deficiency syndrome
  • Neurotoxicity
  • Trolox
  • Tubulin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

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). / Butler, Tracy R.; Smith, Katherine J.; Self, Rachel L.; Braden, Brittany; Prendergast, Mark A.

In: Neurochemical Research, Vol. 36, No. 5, 05.2011, p. 819-828.

Research output: Contribution to journalArticle

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