Abstract
Trauma introduces damaging stressors that compromise protein, lipid, and nucleic acid integrity. Aggregates of unfolded and misfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response (ERSR)/unfolded protein response (UPR) leading to activation of three signaling pathways mediated by PERK, ATF6, and IRE1. Initially, the ERSR/UPR is pro-homeostatic as it globally slows translation while increasing translation of chaperone proteins and inducing ER-associated degradation. If the cellular stress is not controlled, apoptosis is subsequently induced through several mechanisms, of which the most well-described is CHOP. Following spinal cord injury (SCI), mice deficient in CHOP signaling show increased spared white matter and enhanced locomotor recovery by 6 weeks. At 24 hours after SCI, ATF4 and CHOP are upregulated in under perfused microvessels. We observed vascular protection 3 days post-SCI and a significant decrease in macrophage infiltration by the end of the first week. These results suggest that modulating ER-stress signaling in endothelial cells and macrophages may protect against vascular injury and attenuate inflammation post-SCI.
Keywords: Angiogenesis, CHOP, endoplasmic reticulum stress, endothelial cell, inflammation, spinal cord injury, (TRAF2), (HAECs), (PERK), (ECs)
Current Neurovascular Research
Title:Deletion of Endoplasmic Reticulum Stress-Induced CHOP Protects Microvasculature Post-Spinal Cord Injury
Volume: 9 Issue: 4
Author(s): Janelle M. Fassbender, Sujata Saraswat-Ohri, Scott A. Myers, Mark J. Gruenthal, Richard L. Benton and Scott R. Whittemore
Affiliation:
Keywords: Angiogenesis, CHOP, endoplasmic reticulum stress, endothelial cell, inflammation, spinal cord injury, (TRAF2), (HAECs), (PERK), (ECs)
Abstract: Trauma introduces damaging stressors that compromise protein, lipid, and nucleic acid integrity. Aggregates of unfolded and misfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response (ERSR)/unfolded protein response (UPR) leading to activation of three signaling pathways mediated by PERK, ATF6, and IRE1. Initially, the ERSR/UPR is pro-homeostatic as it globally slows translation while increasing translation of chaperone proteins and inducing ER-associated degradation. If the cellular stress is not controlled, apoptosis is subsequently induced through several mechanisms, of which the most well-described is CHOP. Following spinal cord injury (SCI), mice deficient in CHOP signaling show increased spared white matter and enhanced locomotor recovery by 6 weeks. At 24 hours after SCI, ATF4 and CHOP are upregulated in under perfused microvessels. We observed vascular protection 3 days post-SCI and a significant decrease in macrophage infiltration by the end of the first week. These results suggest that modulating ER-stress signaling in endothelial cells and macrophages may protect against vascular injury and attenuate inflammation post-SCI.
Export Options
About this article
Cite this article as:
M. Fassbender Janelle, Saraswat-Ohri Sujata, A. Myers Scott, J. Gruenthal Mark, L. Benton Richard and R. Whittemore Scott, Deletion of Endoplasmic Reticulum Stress-Induced CHOP Protects Microvasculature Post-Spinal Cord Injury, Current Neurovascular Research 2012; 9 (4) . https://dx.doi.org/10.2174/156720212803530627
DOI https://dx.doi.org/10.2174/156720212803530627 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- 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
Related Articles
-
The Protective Effects of Natural Products on Blood-Brain Barrier Breakdown
Current Medicinal Chemistry Voltage-Gated Sodium Channels in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Animal Models in Neurology: Drawbacks and Opportunities
Current Pharmaceutical Design Palmitoylethanolamide in Homeostatic and Traumatic Central Nervous System Injuries
CNS & Neurological Disorders - Drug Targets Prevention of Endothelial Cell Injury by Activated Protein C: The Molecular Mechanism(s) and Therapeutic Implications
Current Vascular Pharmacology The Anandamide Degradation System as Potential Target for the Treatment of Central Nervous System Related Disorders
Current Medicinal Chemistry - Central Nervous System Agents Prostaglandins and Cyclooxygenases in Glial Cells During Brain Inflammation
Current Drug Targets - Inflammation & Allergy The Concurrent Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells on Gentamycin-induced Hepatorenal Toxicity in Rats
Current Stem Cell Research & Therapy Mechanisms of Neural Stem Cell Fate Determination: Extracellular Cues and Intracellular Programs
Current Stem Cell Research & Therapy Molecular and Biochemical Features in Alzheimers Disease
Current Pharmaceutical Design Orofacial Pain and Mastication in Dementia
Current Alzheimer Research Phosphatidylserine and Curcumin Act Synergistically to Down-Regulate Release of Interleukin-1β from Lipopolysaccharide-Stimulated Cortical Primary Microglial Cells
CNS & Neurological Disorders - Drug Targets Current Evaluation of the Millennium Phytomedicine- Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine
Current Medicinal Chemistry Gut-Brain Axis in Gastric Mucosal Damage and Protection
Current Neuropharmacology Role of Pituitary Adenylate Cyclase-Activating Polypeptide in Nociception and Migraine
CNS & Neurological Disorders - Drug Targets MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders
Current Genomics Huntingtons Disease: The Value of Transcranial Meganetic Stimulation
Current Medicinal Chemistry Delivering RNA Interference to the Mammalian Brain
Current Gene Therapy The Relationship of Developmental Changes in White Matter to the Onset of Psychosis
Current Pharmaceutical Design Virus-Associated Vasculitides
Current Immunology Reviews (Discontinued)