Abstract
The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.
Keywords: Cyclooxygenase, Prostaglandins, Signaling, nitric oxide releasing NSAID, carcinogenesis, NOS system
Current Medicinal Chemistry
Title:Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling
Volume: 23 Issue: 24
Author(s): Andrey Sorokin
Affiliation:
Keywords: Cyclooxygenase, Prostaglandins, Signaling, nitric oxide releasing NSAID, carcinogenesis, NOS system
Abstract: The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.
Export Options
About this article
Cite this article as:
Sorokin Andrey, Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling, Current Medicinal Chemistry 2016; 23 (24) . https://dx.doi.org/10.2174/0929867323666160729105312
DOI https://dx.doi.org/10.2174/0929867323666160729105312 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Multiple Faceted Roles of Cocaine in Potentiation of HAND
Current HIV Research Catastrophic Antiphospholipid Syndrome - 20 Years Later
Current Rheumatology Reviews Oxidative Brain Damage by Peroxynitrite in Bacterial Meningitis: A Target for Adjunctive Therapy?
Current Medicinal Chemistry - Central Nervous System Agents Commentary: Perivascular Fat and Improved Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Surgery
Current Vascular Pharmacology The Perfect Storm: A Rheumatologist's Point of View on COVID-19 Infection
Current Rheumatology Reviews Immunopathology of Brucella Infection
Recent Patents on Anti-Infective Drug Discovery Intestinal Microbiota: A Regulator of Intestinal Inflammation and Cardiac Ischemia?
Current Drug Targets Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease
Current Pharmaceutical Design Heart Disease in Patients with HIV/AIDS-An Emerging Clinical Problem
Current Cardiology Reviews Therapeutic Strategies Targeting Endothelial Function in Humans:Clinical Implications
Current Vascular Pharmacology The Role of Disproportionality Analysis of Pharmacovigilance Databases in Safety Regulatory Actions: a Systematic Review
Current Drug Safety Treatment of Viral Encephalitis
Central Nervous System Agents in Medicinal Chemistry Rashes, Sniffles, and Stroke: A Role for Infection in Ischemic Stroke of Childhood
Infectious Disorders - Drug Targets Virus-Associated Vasculitides: An Update
Current Immunology Reviews (Discontinued) Peroxisome Proliferator-Activated Receptor (PPAR) in Metabolic Syndrome and Type 2 Diabetes Mellitus
Current Diabetes Reviews Pathologic Findings of Autoimmune Pancreatitis and IgG4-Related Disease
Current Immunology Reviews (Discontinued) Pathogenesis and Therapeutics of Interstitial Lung Disease in Systemic Sclerosis
Current Rheumatology Reviews Deciphering Supportive Treatment Strategies for Toxic Epidermal Necrolysis
Current Drug Safety Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India
Current Vascular Pharmacology Gold Salts Therapy in Respiratory Diseases
Current Respiratory Medicine Reviews