Abstract
In the last decade, it has become recognized that reactive oxygen species (ROS) play important roles in the multiple biological processes involved in the pathophysiology of chronic inflammation such as cell proliferation, adhesion molecule expression, cytokine and chemoattractant production and matrix metalloproteinase generation. Intracellular redox homeostasis is maintained by balancing the production of ROS with their removal through cellular antioxidant defense systems. The antioxidant response element (ARE) is a cis-acting DNA regulatory element located in the regulatory regions of multiple genes including phase II detoxification enzymes as well as antioxidant proteins including glutathione-S-transferases, NAD(P)H:quinone oxidoreductase-1, γ-glutamylcysteine synthase, ferritin, and heme oxygenase-1. Nrf2 is the primary transcription factor that binds to the ARE, and through heterodimerization with other leucine-zipper containing transcription factors, activates the expression of these genes. It is evident that activation of ARE-regulated genes contributes to the regulation of cellular antioxidant defense systems. More importantly, there is a growing body of evidence suggesting that modulation of these cytoprotective genes has profound effects on immune and inflammatory responses. Activation of cytoprotective Nrf2 / ARE-regulated genes can suppress inflammatory responses, whereas decreased expression of these genes results in autoimmune disease and enhanced inflammatory responses to oxidant insults. Thus, coordinate induction of cytoprotective genes through Nrf2 / ARE pathway may represent a novel therapeutic approach for the treatment of immune and inflammatory diseases.
Keywords: antioxidant response element, reactive oxygen species, nrf2, inflammation
Current Pharmaceutical Design
Title: Induction of Cytoprotective Genes Through Nrf2 / Antioxidant Response Element Pathway: A New Therapeutic Approach for the Treatment of Inflammatory Diseases
Volume: 10 Issue: 8
Author(s): Xi-Lin Chen and Charles Kunsch
Affiliation:
Keywords: antioxidant response element, reactive oxygen species, nrf2, inflammation
Abstract: In the last decade, it has become recognized that reactive oxygen species (ROS) play important roles in the multiple biological processes involved in the pathophysiology of chronic inflammation such as cell proliferation, adhesion molecule expression, cytokine and chemoattractant production and matrix metalloproteinase generation. Intracellular redox homeostasis is maintained by balancing the production of ROS with their removal through cellular antioxidant defense systems. The antioxidant response element (ARE) is a cis-acting DNA regulatory element located in the regulatory regions of multiple genes including phase II detoxification enzymes as well as antioxidant proteins including glutathione-S-transferases, NAD(P)H:quinone oxidoreductase-1, γ-glutamylcysteine synthase, ferritin, and heme oxygenase-1. Nrf2 is the primary transcription factor that binds to the ARE, and through heterodimerization with other leucine-zipper containing transcription factors, activates the expression of these genes. It is evident that activation of ARE-regulated genes contributes to the regulation of cellular antioxidant defense systems. More importantly, there is a growing body of evidence suggesting that modulation of these cytoprotective genes has profound effects on immune and inflammatory responses. Activation of cytoprotective Nrf2 / ARE-regulated genes can suppress inflammatory responses, whereas decreased expression of these genes results in autoimmune disease and enhanced inflammatory responses to oxidant insults. Thus, coordinate induction of cytoprotective genes through Nrf2 / ARE pathway may represent a novel therapeutic approach for the treatment of immune and inflammatory diseases.
Export Options
About this article
Cite this article as:
Chen Xi-Lin and Kunsch Charles, Induction of Cytoprotective Genes Through Nrf2 / Antioxidant Response Element Pathway: A New Therapeutic Approach for the Treatment of Inflammatory Diseases, Current Pharmaceutical Design 2004; 10 (8) . https://dx.doi.org/10.2174/1381612043452901
DOI https://dx.doi.org/10.2174/1381612043452901 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Editorial [Hot Topic: New Prospects for Treatment of Autoimmune Diseases (Executive Guest Editor: Alessandra Fierabracci)]
Current Pharmaceutical Design Myelin Sheaths and Autoimmune Response Induced by Myelin Proteins and Alphaviruses. I. Physicochemical Background
Current Medicinal Chemistry To Cardiovascular Disease and Beyond: New Therapeutic Perspectives of Statins in Autoimmune Diseases and Cancer
Current Drug Targets Natural and Induced Regulatory T Cells: Targets for Immunotherapy of Autoimmune Disease and Allergy
Inflammation & Allergy - Drug Targets (Discontinued) The Impact of Fc Receptors on the Development of Autoimmune Diseases
Current Pharmaceutical Design Emerging Treatment Strategies and Potential Therapeutic Targets in Primary Sjogrens Syndrome
Inflammation & Allergy - Drug Targets (Discontinued) Mouse Models of Autoimmune Diseases - Autoimmune Myocarditis
Current Pharmaceutical Design Spots, Blots, Peaks and Chips: Proteomic Approaches in Autoimmune Diseases
Current Pharmaceutical Design Novel Carriers for Coenzyme Q10 Delivery
Current Drug Delivery Hepatic Manifestations in Juvenile Systemic Lupus Erythematosus
Recent Patents on Inflammation & Allergy Drug Discovery Biological Activities, Mechanisms of Action and Biomedical Prospect of the Antitumor Ether Phospholipid ET-18-OCH3 (Edelfosine), A Proapoptotic Agent in Tumor Cells
Current Drug Metabolism Anti-CCP Antibody Detection Facilitates Early Diagnosis and Prognosis of Rheumatoid Arthritis
Current Rheumatology Reviews T Cell-Activated Signaling Pathways and Locally Produced Cytokines as Potential Targets in Celiac Disease
Current Drug Targets Immune Modulation by Plasmid DNA-mediated Cytokine Gene Transfer
Current Pharmaceutical Design Mesenchymal Stem Cell as a Potential Therapeutic for Inflammatory Bowel Disease- Myth or Reality?
Current Stem Cell Research & Therapy Cardiovascular Involvement in Pediatric Systemic Autoimmune Diseases: The Emerging Role of Noninvasive Cardiovascular Imaging
Inflammation & Allergy - Drug Targets (Discontinued) Local Treatment for Lymphoid Malignancies of the Eye
Anti-Cancer Agents in Medicinal Chemistry Molecular Characteristics of Autoimmune Pancreatitis
Current Pharmaceutical Design Natural Killer T Cells and Autoimmune Disease
Current Molecular Medicine Challenge of Mesenchymal Stem Cells Against Diabetic Foot Ulcer
Current Stem Cell Research & Therapy