Abstract
Human immunodeficiency virus type 1 (HIV-1) Tat protein is a major pathogenic factor in HIV-associated neurological diseases; it exhibits direct neurotoxicity and indirect astrocyte-mediated neurotoxicity. We have shown that Tat alone is capable of activating glial fibrillary acidic protein (GFAP) expression and inducing astrocytosis involving sequential activation of early growth response protein 1 (Egr-1) and p300. In this study, we determined the roles of signal transducer and activator of transcription 3 (STAT3) in Tat-induced GFAP transactivation. STAT3 expression and phosphorylation led to significant increases in GFAP transcription and protein expression. Tat expression was associated with increased STAT3 expression and phosphorylation in Tat-expressing astrocytes and HIV-infected astrocytes. GFAP, Egr-1 and p300 transcription and protein expression all showed positive response to STAT3 and its phosphorylation. Importantly, knockdown of STAT3 resulted in significant decreases in Tat-induced GFAP and Egr-1 transcription and protein expression. Taken together, these findings show that STAT3 is involved in and acts upstream of Egr1 and p300 in the Tat-induced GFAP transactivation cascade and suggest important roles of STAT3 in controlling astrocyte proliferation and activation in the HIV-infected central nervous system.
Current HIV Research
Title:STAT3 and Its Phosphorylation are Involved in HIV-1 Tat-Induced Transactivation of Glial Fibrillary Acidic Protein
Volume: 13 Issue: 1
Author(s): Yan Fan, Khalid Amine Timani and Johnny J. He
Affiliation:
Keywords: Astrocytes, HIV-1 Tat, Egr-1, p300, GFAP, STAT3.
Abstract: Human immunodeficiency virus type 1 (HIV-1) Tat protein is a major pathogenic factor in HIV-associated neurological diseases; it exhibits direct neurotoxicity and indirect astrocyte-mediated neurotoxicity. We have shown that Tat alone is capable of activating glial fibrillary acidic protein (GFAP) expression and inducing astrocytosis involving sequential activation of early growth response protein 1 (Egr-1) and p300. In this study, we determined the roles of signal transducer and activator of transcription 3 (STAT3) in Tat-induced GFAP transactivation. STAT3 expression and phosphorylation led to significant increases in GFAP transcription and protein expression. Tat expression was associated with increased STAT3 expression and phosphorylation in Tat-expressing astrocytes and HIV-infected astrocytes. GFAP, Egr-1 and p300 transcription and protein expression all showed positive response to STAT3 and its phosphorylation. Importantly, knockdown of STAT3 resulted in significant decreases in Tat-induced GFAP and Egr-1 transcription and protein expression. Taken together, these findings show that STAT3 is involved in and acts upstream of Egr1 and p300 in the Tat-induced GFAP transactivation cascade and suggest important roles of STAT3 in controlling astrocyte proliferation and activation in the HIV-infected central nervous system.
Export Options
About this article
Cite this article as:
Fan Yan, Timani Amine Khalid and He J. Johnny, STAT3 and Its Phosphorylation are Involved in HIV-1 Tat-Induced Transactivation of Glial Fibrillary Acidic Protein, Current HIV Research 2015; 13 (1) . https://dx.doi.org/10.2174/1570162X13666150121115804
DOI https://dx.doi.org/10.2174/1570162X13666150121115804 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
Call for Papers in Thematic Issues
Management of HIV: Management of HIV: old challenges and new needs
The aim of this thematic issue is to provide the most recent updates regarding the effective management of HIV infection. Antiretroviral therapy (ART) has significantly decreased HIV-related mortality, leading to an enhancement in the quality of life and life expectancy for people living with HIV (PLWH). Despite the numerous advancements ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Nanowired Drug Delivery of Antioxidant Compound H-290/51 Enhances Neuroprotection in Hyperthermia-Induced Neurotoxicity
CNS & Neurological Disorders - Drug Targets Pathways by Which Aβ Facilitates Tau Pathology
Current Alzheimer Research STING Activation and its Application in Immuno-Oncology
Current Topics in Medicinal Chemistry Predicting the Potential Public Health Impact of Disease-Modifying HIV Vaccines in South Africa: The Problem of Subtypes
Current Drug Targets - Infectious Disorders Autoantibodies Among HIV-1 Infected Individuals and the Effect of Anti-Retroviral Therapy (ART) on It
Current HIV Research Virus-Based RNA Silencing Agents and Virus-Derived Expression Vectors as Gene Therapy Vehicles
Recent Patents on Biotechnology Tetracyclines and Pulmonary Inflammation
Endocrine, Metabolic & Immune Disorders - Drug Targets The Potential for Genetically Altered Microglia to Influence Glioma Treatment
CNS & Neurological Disorders - Drug Targets Nanoparticle- and Liposome-carried Drugs: New Strategies for Active Targeting and Drug Delivery Across Blood-brain Barrier
Current Drug Metabolism Myelin Sheaths and Autoimmune Response Induced by Myelin Proteins and Alphaviruses. I. Physicochemical Background
Current Medicinal Chemistry Natural Products Homoharringtonine and Emetine Alkaloids as SARS-CoV-2 Treatment Options
Current Pharmaceutical Design Novel and Viable Acetylcholinesterase Target Site for Developing Effective and Environmentally Safe Insecticides
Current Drug Targets Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design Dietary Antioxidants: Immunity and Host Defense
Current Topics in Medicinal Chemistry A Review on Clinical Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Natalizumab: A Humanized Anti-α4 Integrin Monoclonal Antibody
Current Drug Metabolism Pharmacological Treatment of Mild Cognitive Impairment as a Prodromal Syndrome of Alzheimer´s Disease
Current Neuropharmacology Microbial Sensors Based on Nanostructures
Recent Patents on Nanomedicine Exosomes and the Emerging Field of Exosome-Based Gene Therapy
Current Gene Therapy Therapeutic Perspectives of Drugs Targeting Toll-Like Receptors Based on Immune Physiopathology Theory of Alzheimers Disease
CNS & Neurological Disorders - Drug Targets AIDS-Defining Illnesses: A Comparison Between Before and After Commencement of Highly Active Antiretroviral Therapy (HAART)
Current HIV Research