Involvement of Inositol 1,4,5‐Trisphosphate‐Regulated Stores of Intracellular Calcium in Calcium Dysregulation and Neuron Cell Death Caused by HIV‐1 Protein Tat

@article{Haughey1999InvolvementOI,
  title={Involvement of Inositol 1,4,5‐Trisphosphate‐Regulated Stores of Intracellular Calcium in Calcium Dysregulation and Neuron Cell Death Caused by HIV‐1 Protein Tat},
  author={Norman J. Haughey and Clark P. Holden and Avindra Nath and Jonathan D. Geiger},
  journal={Journal of Neurochemistry},
  year={1999},
  volume={73}
}
Abstract : HIV‐1 infection commonly leads to neuronal cell death and a debilitating syndrome known as AIDS‐related dementia complex. The HIV‐1 protein Tat is neurotoxic, and because cell survival is affected by the intracellular calcium concentration ([Ca2+]i), we determined mechanisms by which Tat increased [Ca2+]i and the involvement of these mechanisms in Tat‐induced neurotoxicity. Tat increased [Ca2+]i dose‐dependently in cultured human fetal neurons and astrocytes. In neurons, but not… 
Release of Calcium from Inositol 1,4,5-Trisphosphate Receptor-Regulated Stores by HIV-1 Tat Regulates TNF-α Production in Human Macrophages1
TLDR
In macrophages, Tat-induced release of calcium from IP3-sensitive intracellular stores and activation of nonconventional PKC isoforms play an important role in Tat- induced TNF-α production.
HIV‐1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity
TLDR
It is suggested that NMDA receptors play an important role in Tat neurotoxicity and the mechanisms identified may provide additional therapeutic targets for the treatment of HIV‐1 associated dementia.
HIV‐1 protein Tat reduces the glutamate‐induced intracellular Ca2+ increase in cultured cortical astrocytes
TLDR
The data suggest that Tat and TNFα, both by itself and synergistically, induce astroglial dysfunction and that Tat acts upon induction of a so far unknown cellular gene whoes gene product causes the reduction of glutamate responses.
Astrocytes mediate HIV‐1 Tat‐induced neuronal damage via ligand‐gated ion channel P2X7R
TLDR
Novel insights are provided into astrocyte‐mediated neuropathogenesis in HIV‐1 infection and a novel target for therapeutic management of neuroAIDS is provided.
MCP‐1 (CCL2) protects human neurons and astrocytes from NMDA or HIV‐tat‐induced apoptosis
TLDR
Monocyte chemoattractant protein‐1 (MCP‐1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA‐induced apoptosis, indicating that MCP‐ 1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.
Inositol 1,4,5‐trisphosphate receptor (type 1) phosphorylation and modulation by Cdc2
TLDR
It is shown that cdc2/CyB, a critical regulator of eukaryotic cell cycle progression, phosphorylates IP3R1 in vitro and in vivo at both Ser421 and Thr799 and that this phosphorylation increases IP3 binding.
Synergistic increases in intracellular Ca2+, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat
TLDR
The findings suggest that opiates may increase the vulnerability of the CNS to viral entry and ensuing HIV encephalitis by synergistically increasing MCP‐1 and RANTES release by astrocytes.
Activation of the Adenosine A1 Receptor Inhibits HIV-1 Tat-Induced Apoptosis by Reducing Nuclear Factor-κB Activation and Inducible Nitric-Oxide Synthase
TLDR
It is demonstrated that the A1AR protects against HIV-1 toxicity by inhibiting NF-κB, thereby reducing the expression of iNOS and NO radicals and neuronal apoptosis.
The immunophilin ligand GPI1046 protects neurons from the lethal effects of the HIV‐1 proteins gp120 and Tat by modulating endoplasmic reticulum calcium load
TLDR
It is found that non‐immunosuppressive immunophilin ligands may be useful neuroprotective drugs in HIV dementia and GPI1046 reduced the total ER calcium load.
...
...

References

SHOWING 1-10 OF 81 REFERENCES
HIV-1 Protein Tat Induces Apoptosis of Hippocampal Neurons by a Mechanism Involving Caspase Activation, Calcium Overload, and Oxidative Stress
TLDR
The data demonstrate that Tat can induce neuronal apoptosis by a mechanism involving disruption of calcium homeostasis, caspase activation, and mitochondrial calcium uptake and ROS accumulation, and indicates an important role for mitochondrial membrane permeability transition in Tat-induced apoptosis.
Human immunodeficiency virus type 1 tat activates non—N‐methyl‐D‐aspartate excitatory amino acid receptors and causes neurotoxicity
TLDR
Tat, released from HIVv1vinfected cells, may be an important mediator of neurotoxicity observed in HIV1 encephalopathy, and the N‐methylvD‐aspartate receptor antagonist had little effect on Tatvinduced depolarizations but did provide protection from Tat neurotoxicity.
T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis.
TLDR
It is shown that IP3R1-deficient T cells are resistant to apoptosis induced by dexamethasone, TCR stimulation, ionizing radiation, and Fas, indicating that extracellular calcium influx is not required.
Neurotoxicity of the human immunodeficiency virus type 1 Tat transactivator to PC12 cells requires the Tat amino acid 49‐58 basic domain
TLDR
It is shown that Tat toxicity is inhibited by cotreatment with excess Tat49‐58, suggesting Tat neurotoxicity requires binding to its surface ligand, and chloroquine, which increases nuclear accumulation of Tat, enhances Tat toxicity to PC 12 cells, suggesting that Tat internalization is a required step in the mechanism of its toxicity.
Lymphocyte Apoptosis: Mediation by Increased Type 3 Inositol 1,4,5-Trisphosphate Receptor
B and T lymphocytes undergoing apoptosis in response to anti-immunoglobulin M antibodies and dexamethasone, respectively, were found to have increased amounts of messenger RNA for the inositol
Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: implications for AIDS pathology.
TLDR
It is demonstrated, by a variety of approaches, that Vpr added extracellularly to intact cells does indeed form ion channels and its mechanistic basis may have important implications for neuropathologies in AIDS patients who possess significant amounts of Vpr in the cerebrospinal fluid.
Neuronal excitatory properties of human immunodeficiency virus type 1 tat protein
Extracellular HIV-1 Tat Protein Induces a Rapid and Selective Activation of Protein Kinase C (PKC)-α, -ϵ, and -ζ Isoforms in PC12 Cells
TLDR
It is demonstrated that extracellular Tat shows a cytokine-like activity in PC12 cells, being able to trigger an intracellular signalling cascade which involves PKC-α, -ϵ, and -ζ.
Protein kinase C‐mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes.
TLDR
A role for metabotropic glutamate receptors in modulation of NMDA‐mediated processes is suggested in Xenopus oocytes injected with rat brain RNA and under conditions that eliminate the oocyte's endogenous calcium‐dependent chloride current.
...
...