Abstract
Extensive nerve cell death occurs during the development of the central nervous system as well as in episodes of trauma and in neurodegenerative disease. The mechanistic details of how these cells die are poorly understood. Here we describe a unique oxidative stress-induced programmed cell death pathway called oxytosis, and outline pharmacological approaches which interfere with its execution. Oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake through the cystine/glutamate antiporter leading to a depletion of glutathione, is used as an example of oxytosis. It is shown that there is a sequential requirement for de novo macromolecular synthesis, lipoxygenase activation, reactive oxygen species production, and the opening of cGMP-gated channels which allow the influx of extracellular calcium. The translation initiation factor eIF2α plays a central role in this pathway by regulating the levels of glutathione. Finally, examples are given in which the reduction in glutathione, the production of reactive oxygen species, and calcium influx can be experimentally manipulated to prevent cell death. Data are reviewed which suggest that oxytosis may be involved in nerve cell death associated with nervous system trauma and disease.
Current Topics in Medicinal Chemistry
Title: Oxytosis: A Novel Form of Programmed Cell Death
Volume: 1 Issue: 6
Author(s): Shirlee Tan, David Schubert and Pamela Maher
Affiliation:
Abstract: Extensive nerve cell death occurs during the development of the central nervous system as well as in episodes of trauma and in neurodegenerative disease. The mechanistic details of how these cells die are poorly understood. Here we describe a unique oxidative stress-induced programmed cell death pathway called oxytosis, and outline pharmacological approaches which interfere with its execution. Oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake through the cystine/glutamate antiporter leading to a depletion of glutathione, is used as an example of oxytosis. It is shown that there is a sequential requirement for de novo macromolecular synthesis, lipoxygenase activation, reactive oxygen species production, and the opening of cGMP-gated channels which allow the influx of extracellular calcium. The translation initiation factor eIF2α plays a central role in this pathway by regulating the levels of glutathione. Finally, examples are given in which the reduction in glutathione, the production of reactive oxygen species, and calcium influx can be experimentally manipulated to prevent cell death. Data are reviewed which suggest that oxytosis may be involved in nerve cell death associated with nervous system trauma and disease.
Export Options
About this article
Cite this article as:
Shirlee Tan , David Schubert and Pamela Maher , Oxytosis: A Novel Form of Programmed Cell Death, Current Topics in Medicinal Chemistry 2001; 1 (6) . https://dx.doi.org/10.2174/1568026013394741
DOI https://dx.doi.org/10.2174/1568026013394741 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Integrated Analysis of Transcriptomic and Proteomic Data
Current Genomics Beta-Amyloid, Oxidative Stress and Down Syndrome
Current Alzheimer Research Brain Adaptation to Stressful Stimuli: A New Perspective on Potential Therapeutic Approaches Based on BDNF and NMDA Receptors
CNS & Neurological Disorders - Drug Targets Peroxisome Proliferator Activated Receptor Gamma Coactivator 1 Alpha: An Emerging Target for Neuroprotection in Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets NAD(P) Biosynthesis Enzymes as Potential Targets for Selective Drug Design
Current Medicinal Chemistry Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach
Current Neuropharmacology Targeting PPARalpha in Alzheimer's Disease
Current Alzheimer Research Role of the APP Non-Amyloidogenic Signaling Pathway and Targeting α-Secretase as an Alternative Drug Target for Treatment of Alzheimers Disease
Current Medicinal Chemistry Biohybrid Membrane Systems for Testing Molecules and Stem Cell Therapy in Neuronal Tissue Engineering
Current Pharmaceutical Design Cytokines in Neuroinflammation and Alzheimers Disease
Current Drug Targets Intracellular Redox Signaling as Therapeutic Target for Novel Antiviral Strategy
Current Pharmaceutical Design Recent Patents on Proteases and Kinases as Anti-Infective Agents: A Review
Recent Patents on Anti-Infective Drug Discovery “Connecting the Dots” from Blood Brain Barrier Dysfunction to Neuroinflammation and Alzheimer’s Disease
Current Neurovascular Research The Effects of Creatine Supplementation and Physical Exercise on Traumatic Brain Injury
Mini-Reviews in Medicinal Chemistry Nitric Oxide, Peroxynitrite, Peroxynitrous Acid, Nitroxyl, Nitrogen Dioxide, Nitrous Oxide: Biochemical Mechanisms and Bioaction
Current Bioactive Compounds Perspectives in Nanomedicine-Based Research Towards Cancer Therapies
Current Nanoscience Nanoparticle Enabled Drug Delivery Across the Blood Brain Barrier: in vivo and in vitro Models, Opportunities and Challenges
Current Pharmaceutical Biotechnology Subject Index to Volume 1
Current Neurovascular Research Acetylcholinesterase Inhibitor Donepezil Effects on Plasma β-Hydroxybutyrate Levels in the Treatment of Alzheimer’s Disease
Current Alzheimer Research Editorial (Thematic Issue: Disease Control and Active and Healthy Ageing: New Paradigms of Therapeutic Strategy)
Current Pharmaceutical Design