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
-
Tetramethylpyrazine Facilitates Functional Recovery after Spinal Cord Injury by Inhibiting MMP2, MMP9, and Vascular Endothelial Cell Apoptosis
Current Neurovascular Research Patent Selections
Recent Patents on Medical Imaging Emerging Use of Nanotechnology in the Treatment of Neurological Disorders
Current Pharmaceutical Design In Vitro and In Vivo Models of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Immunomodulatory Properties of Antibiotics
Current Molecular Pharmacology The Role of Minocycline in Ischemia-Reperfusion Injury: A Comprehensive Review of an Old Drug with New Implications
Recent Patents on Cardiovascular Drug Discovery The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications
Current Medicinal Chemistry The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry Strategies to Direct Angiogenesis within Scaffolds for Bone Tissue Engineering
Current Pharmaceutical Design Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19
Current Neuropharmacology Emerging Therapies for Diabetic Neuropathy: A Clinical Overview
Current Diabetes Reviews Inflammatory Caspases: Targets for Novel Therapies
Current Pharmaceutical Design Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics
Current Neuropharmacology The Valsalva Maneuver and Alzheimers Disease: Is there a link?
Current Alzheimer Research The Bioanalytical Molecular Pharmacology of the N-methyl-<sub>D</sub>-Aspartate (NMDA) Receptor Nexus and the Oxygen-Responsive Transcription Factor HIF-1α : Putative Mechanisms and Regulatory Pathways Unravel the Intimate Hypoxia Connection
Current Molecular Pharmacology Is Erectile Dysfunction an Example of Abnormal Endothelial Function?
Current Vascular Pharmacology Can Unconventional Exercise be Helpful in the Treatment, Management and Prevention of Osteosarcopenic Obesity?
Current Aging Science Recent Advances and Patents on Nanoscale Systems and Triggerable Drug Delivery in Medical Devices
Recent Patents on Biomedical Engineering (Discontinued) Potassium Channels as Targets for the Management of Pain
Central Nervous System Agents in Medicinal Chemistry Targeting Ionotropic Glutamate Receptors in the Treatment of Epilepsy
Current Neuropharmacology