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.
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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 |
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