Proliferation inhibition of astrocytes, neurons, and non-glial cells by intracellularly expressed human immunodeficiency virus type 1 (HIV-1) Tat protein

Human immunodeficiency virus type 1 Tat protein is one of the soluble neurotoxins. Most studies have to date focused on Tat as an extracellular molecule and its role in neuronal apoptosis, as recombinant Tat protein is often used in these studies. In this study, we expressed Tat protein in astrocyte...

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Bibliographic Details
Published in:Neuroscience letters 2004-04, Vol.359 (3), p.155-158
Main Authors: Zhou, Betty Y., He, Johnny J.
Format: Article
Language:English
Subjects:
Animals
Anti-proliferation
Astrocytes
Astrocytes - metabolism
Astrocytes - pathology
Biological and medical sciences
Cell Cycle
Cell Cycle Proteins - metabolism
Cell Division
Cell Line
Cell Line, Tumor
Cell Survival
Fundamental and applied biological sciences. Psychology
Growth Inhibitors - metabolism
Human immunodeficiency virus 1
Human immunodeficiency virus type 1
Humans
Intracellular Fluid - metabolism
Kidney - embryology
Kidney - metabolism
Kidney - pathology
Neuroglia - metabolism
Neuroglia - pathology
Neurons
Neurons - metabolism
Neurons - pathology
Rats
Recombinant Proteins - metabolism
Tat
Trans-Activators - genetics
Trans-Activators - metabolism
Vertebrates: nervous system and sense organs
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Summary:Human immunodeficiency virus type 1 Tat protein is one of the soluble neurotoxins. Most studies have to date focused on Tat as an extracellular molecule and its role in neuronal apoptosis, as recombinant Tat protein is often used in these studies. In this study, we expressed Tat protein in astrocytes and neurons, and examined its effects on these cells. We found that Tat expression resulted in growth inhibition of astrocytes, neurons, as well as non-glial cells 293T. We further showed that Tat interacted with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA. These data demonstrate that Tat inhibited cell proliferation when expressed intracellularly, and suggest that Tat interactions with multiple cell cycle regulators may account for this anti-proliferative effect. These results support the notion that Tat-induced neuropathogenesis is mediated by multiple mechanisms involving both intracellular and extracellular Tat protein.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2004.02.012