HIV-1 Tat causes apoptotic death and calcium homeostasis alterations in rat neurons

Rudy Bonavia, Adriana Bajetto, Simone Barbero, Adriana Albini, Douglas M. Noonan, Gennaro Schettini

Research output: Contribution to journalArticle

Abstract

We investigated the role of the HIV-1 protein Tat in AIDS-associated dementia, by studying its toxicity on rat cortical and hippocampal neurons in vitro. We evaluated the involvement of astroglial cells and of caspase transduction pathway in determining Tat toxicity. Here we report that synthetic Tat1-86 induced apoptotic death on cultured rat neurons in a time-dependent manner that was not influenced by glial coculture, and that was abolished by blocking caspase transduction pathway. A microfluorimetric analysis on the Tat excitatory properties on neurons, and its effect on intracellular calcium concentrations, revealed that Tat1-86 induced increase in cytoplasmic free calcium concentrations in rat hippocampal and cortical neurons. This effect required extracellular calcium and was differently reduced by voltage dependent calcium channel blockers and both NMDA and non-NMDA glutamate receptors antagonists. Furthermore, we observed that Tat1-86-treated neurons showed increased sensitivity to the glutamate excitotoxicity. Thus, the Tat-induced neuronal injury seems to occur through a direct interaction of the protein with neurons, requires activation of caspases, and is likely to derive from Tat1-86-induced calcium loads and disruption of glutamatergic transmission.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume288
Issue number2
DOIs
Publication statusPublished - Oct 26 2001

Fingerprint

Neurons
HIV-1
Rats
Cause of Death
Homeostasis
Calcium
Caspases
Toxicity
tat Gene Products
Human Immunodeficiency Virus Proteins
Excitatory Amino Acid Antagonists
Calcium Channel Blockers
N-Methylaspartate
Calcium Channels
Coculture Techniques
Neuroglia
Dementia
Glutamic Acid
Acquired Immunodeficiency Syndrome
Chemical activation

Keywords

  • AIDS Dementia Complex
  • Caspases
  • Glutamate ionotropic receptors
  • Intracellular calcium
  • Neuronal apoptosis
  • Tat
  • Voltage-gated calcium channels

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

HIV-1 Tat causes apoptotic death and calcium homeostasis alterations in rat neurons. / Bonavia, Rudy; Bajetto, Adriana; Barbero, Simone; Albini, Adriana; Noonan, Douglas M.; Schettini, Gennaro.

In: Biochemical and Biophysical Research Communications, Vol. 288, No. 2, 26.10.2001, p. 301-308.

Research output: Contribution to journalArticle

Bonavia, Rudy ; Bajetto, Adriana ; Barbero, Simone ; Albini, Adriana ; Noonan, Douglas M. ; Schettini, Gennaro. / HIV-1 Tat causes apoptotic death and calcium homeostasis alterations in rat neurons. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 288, No. 2. pp. 301-308.
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