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
-
Patent Annotations
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Driving Neural Stem Cells Towards a Desired Phenotype
Current Stem Cell Research & Therapy Dissecting the Diverse Actions of Pro- and Mature Neurotrophins
Current Alzheimer Research Ionotropic Glutamate Receptors & CNS Disorders
CNS & Neurological Disorders - Drug Targets Chemistry and Pharmacology of Bioactive Molecule -Coenzyme Q10: A Brief Note
Current Bioactive Compounds Neuromodulation of the Perinatal Respiratory Network
Current Neuropharmacology Role of PACAP in Neural Stem/Progenitor Cell and Astrocyte: from Neural Development to Neural Repair
Current Pharmaceutical Design Molecular and Biochemical Features in Alzheimers Disease
Current Pharmaceutical Design Trends and Applications of Brain Computer Interfaces
Current Signal Transduction Therapy Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission
Current Medicinal Chemistry Overview of Current Trends and the Future of Thromboprophylaxis in Orthopaedic Surgery
Vascular Disease Prevention (Discontinued) The Role of Methionine Oxidation/Reduction in the Regulation of Immune Response
Current Signal Transduction Therapy The Role of Cnidaria in Drug Discovery. A Review on CNS Implications and New Perspectives
Recent Patents on CNS Drug Discovery (Discontinued) Advances in Neuroimaging for HIV-1 Associated Neurological Dysfunction: Clues to the Diagnosis, Pathogenesis and Therapeutic Monitoring
Current HIV Research Bone Regeneration and Repair
Current Stem Cell Research & Therapy Extraction and Evaluation of Anti-inflammatory and Analgesic Activity of Mimosa rubicaulis in Swiss Albino Rats
Anti-Infective Agents Endovascular Therapeutic Embolisation: An Overview of Occluding Agents and their Effects on Embolised Tissues
Current Vascular Pharmacology Human Amnion–Derived Cells as a Reliable Source of Stem Cells
Current Molecular Medicine Covalently and Ionically Crosslinked Chitosan Nanogels for Drug Delivery
Current Pharmaceutical Design The Role of Endocannabinoids in Pain Modulation and the Therapeutic Potential of Inhibiting their Enzymatic Degradation
Current Pharmaceutical Biotechnology