Abstract
Cystic fibrosis (CF) is a multisystem disease associated with mutations in the gene that encodes the CF transmembrane conductance regulatory (CFTR) protein. The majority of wild-type CFTR and virtually all mutant ΔF508 CFTR are degraded before reaching the cell surface. Certain agents and conditions that increase expression and maturation of CFTR enable the protein to function at the cell surface. We and several research groups have reported that S-nitrosoglutathione (GSNO), a class of endogenous S-nitrosothiols, increases the maturation and function of CFTR in human airway epithelial cells. S-nitrosothiols (SNOs) are endogenous molecules with several cell signaling effects and potential relevance to human lung disease. SNOs are normally present in the human airway and have beneficial effects on lung function. Biochemical evidence suggests that SNOs act on post-translational protein modifications through mechanisms involving S-nitrosylation reactions. S-nitrosylation reactions are increasingly recognized to represent metabolically regulated cell signaling processes. Airway epithelial S-nitrosylation signaling disorders have been observed in a range of diseases, including CF. SNO levels are low in CF patients and normal physiological concentrations are effective in increasing CFTR maturation. The mechanisms by which SNOs improve CFTR expression appear to be novel. However, the precise mechanisms by which SNOs exert their beneficial effects are poorly understood. In the near future, we expect to identify the novel mechanisms by which SNO augments CFTR maturation. This information will be critical for optimizing the design and dosing of SNOs that might be used as CFTR corrector therapies in clinical trials.
Keywords: Cystic fibrosis, CFTR, S-nitrosothiols, S-nitrosylation, molecular therapy.
Current Pharmaceutical Design
Title:Novel S-Nitrosothiols Have Potential Therapeutic Uses for Cystic Fibrosis
Volume: 19 Issue: 19
Author(s): Khalequz Zaman, Maya Fraser-Butler and Deric Bennett
Affiliation:
Keywords: Cystic fibrosis, CFTR, S-nitrosothiols, S-nitrosylation, molecular therapy.
Abstract: Cystic fibrosis (CF) is a multisystem disease associated with mutations in the gene that encodes the CF transmembrane conductance regulatory (CFTR) protein. The majority of wild-type CFTR and virtually all mutant ΔF508 CFTR are degraded before reaching the cell surface. Certain agents and conditions that increase expression and maturation of CFTR enable the protein to function at the cell surface. We and several research groups have reported that S-nitrosoglutathione (GSNO), a class of endogenous S-nitrosothiols, increases the maturation and function of CFTR in human airway epithelial cells. S-nitrosothiols (SNOs) are endogenous molecules with several cell signaling effects and potential relevance to human lung disease. SNOs are normally present in the human airway and have beneficial effects on lung function. Biochemical evidence suggests that SNOs act on post-translational protein modifications through mechanisms involving S-nitrosylation reactions. S-nitrosylation reactions are increasingly recognized to represent metabolically regulated cell signaling processes. Airway epithelial S-nitrosylation signaling disorders have been observed in a range of diseases, including CF. SNO levels are low in CF patients and normal physiological concentrations are effective in increasing CFTR maturation. The mechanisms by which SNOs improve CFTR expression appear to be novel. However, the precise mechanisms by which SNOs exert their beneficial effects are poorly understood. In the near future, we expect to identify the novel mechanisms by which SNO augments CFTR maturation. This information will be critical for optimizing the design and dosing of SNOs that might be used as CFTR corrector therapies in clinical trials.
Export Options
About this article
Cite this article as:
Zaman Khalequz, Fraser-Butler Maya and Bennett Deric, Novel S-Nitrosothiols Have Potential Therapeutic Uses for Cystic Fibrosis, Current Pharmaceutical Design 2013; 19 (19) . https://dx.doi.org/10.2174/13816128113199990319
DOI https://dx.doi.org/10.2174/13816128113199990319 |
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
-
A Viewpoint on Potential Biomarkers for Infectious COVID-19 Severity: An Updated Literature Survey
Infectious Disorders - Drug Targets Electroporation Gene Therapy: New Developments In Vivo and In Vitro
Current Gene Therapy TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies
CNS & Neurological Disorders - Drug Targets Current Progress in Antifibroitcs
Current Medicinal Chemistry Polarization of Cytokine Profile from Th1 into Th2 Along Colorectal Adenoma- Carcinoma Sequence: Implications for the Biotherapeutic Target?
Inflammation & Allergy - Drug Targets (Discontinued) NS5A - From Obscurity to New Target for HCV Therapy
Recent Patents on Anti-Infective Drug Discovery The Potential of Hydrogen for Improving Mental Disorders
Current Pharmaceutical Design Predicting Efficacy and Toxicity in the Era of Targeted Therapy: Focus on Anti-EGFR and Anti-VEGF Molecules
Current Drug Metabolism Low Level Laser Therapy [LLLT] in Inflammatory and Rheumatic Diseases:A Review of Therapeutic Mechanisms
Current Rheumatology Reviews Potential of Anti-inflammatory Molecules in the Chemoprevention of Breast Cancer
Recent Advances in Inflammation & Allergy Drug Discovery Vandetanib, A Dual Inhibitor of VEGFR and EGFR Tyrosine Kinase Activity
Current Cancer Therapy Reviews Synthesis and Biological Activity of New Tricyclic Purine Derivatives Obtained by Intramolecular N-7 Alkylation
Letters in Drug Design & Discovery The Physiology of Nitric Oxide: Control and Consequences
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design The Role of P2Y<sub>12</sub> Receptor and Activated Platelets During Inflammation
Current Drug Targets Use of Antiplatelet Drugs in the Treatment of Acute Coronary Syndromes
Cardiovascular & Hematological Disorders-Drug Targets Immunopotentiation for Bacterial Biodefense
Current Topics in Medicinal Chemistry Diagnosis and Therapeutic Approaches to Transthyretin Amyloidosis
Current Medicinal Chemistry Vitamins B1, B2, B3 and B9 – Occurrence, Biosynthesis Pathways and Functions in Human Nutrition
Mini-Reviews in Medicinal Chemistry Headache in Multiple Sclerosis - Pharmacological Aspects
Current Pharmaceutical Design