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
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
Current Neuropharmacology Editorial (Thematic Issue: New Approaches to the Treatment of Alzheimer's Disease)
Current Topics in Medicinal Chemistry Naturally Inspired Pyrimidines Analogues for Alzheimer’s Disease
Current Neuropharmacology IAPs, their Antagonists and their Role in Neurological Disease and Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Antioxidants and Pro-Antioxidants Network: An Overview
Current Pharmaceutical Design Modern Pathology: Protein Mis-Folding and Mis-Processing in Complex Disease
Current Protein & Peptide Science Shikimate Kinase (EC 2.7.1.71) from Mycobacterium tuberculosis: Kinetics and Structural Dynamics of a Potential Molecular Target for Drug Development
Current Medicinal Chemistry Targeting Oxidative Stress Component in the Therapeutics of Epilepsy
Current Topics in Medicinal Chemistry Regulation of GABA Neurotransmission by Glutamic Acid Decarboxylase (GAD)
Current Pharmaceutical Design The Two Faces of Iminoalditols: Powerful Inhibitors Trigger Glycosidase Activation
Current Enzyme Inhibition “Metabolic Aspects” In Inflammatory Bowel Diseases
Current Drug Delivery Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase Pathways
Current Neuropharmacology Hyperphosphorylation of Microtubule-Associated Protein Tau: A Promising Therapeutic Target for Alzheimer Disease
Current Medicinal Chemistry Melatonin and Respiratory Diseases: A Review
Current Topics in Medicinal Chemistry New Proposals for Treatment Sporadic Alzheimers Disease
Central Nervous System Agents in Medicinal Chemistry NAD Precursors, Mitochondria Targeting Compounds and ADP-Ribosylation Inhibitors in Treatment of Inflammatory Diseases and Cancer
Current Medicinal Chemistry Differential Susceptibility of Naive and Differentiated PC-12 Cells to Methylglyoxal-Induced Apoptosis: Influence of Cellular Redox
Current Neurovascular Research The Role of IRE1 Signaling in the Central Nervous System Diseases
Current Neuropharmacology Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry Neuroprotection by NMDA Receptor Antagonists in a Variety of Neuropathologies
Current Drug Targets