10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer’s disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days. Additionally, chronic morphine treatment resulted in the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). More importantly, inhibiting either one of the three cascades could attenuate the development of morphine tolerance. Taken together, our results suggest that ER stress in spinal cord might contribute to the development of morphine tolerance. These findings implicate a potential clinical strategy for preventing morphine tolerance and may contribute to expanding the morphine usage in clinic.

          Related collections

          Most cited references58

          • Record: found
          • Abstract: found
          • Article: not found

          Endoplasmic reticulum stress: cell life and death decisions.

          C. Xu (2005)
          Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged. The mechanisms by which ER stress leads to cell death remain enigmatic, with multiple potential participants described but little clarity about which specific death effectors dominate in particular cellular contexts. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Endoplasmic reticulum stress in immunity.

            Immune responses occur in the midst of a variety of cellular stresses that can severely perturb endoplasmic reticulum (ER) function. The unfolded protein response is a three-pronged signaling axis dedicated to preserving ER homeostasis. In this review, we highlight many important and emerging functional roles for ER stress in immunity, focusing on how the bidirectional cross talk between immunological processes and basic cell biology leads to pleiotropic signaling outcomes and enhanced sensitivity to inflammatory stimuli. We also discuss how dysregulated ER stress responses can provoke many diseases, including autoimmunity, firmly positioning the unfolded protein response as a major therapeutic target in human disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Form follows function: the importance of endoplasmic reticulum shape.

              The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Mol Neurosci
                Front Mol Neurosci
                Front. Mol. Neurosci.
                Frontiers in Molecular Neuroscience
                Frontiers Media S.A.
                1662-5099
                06 March 2018
                2018
                : 11
                : 72
                Affiliations
                [1] 1Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [2] 2Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei General Hospital , Wuhan, China
                Author notes

                Edited by: Guilherme Lucas, University of São Paulo, Brazil

                Reviewed by: Massimo Ubaldi, University of Camerino, Italy; Zhouguang Wang, Wenzhou Medical University, China

                *Correspondence: Feng Gao, 13971587381@ 123456163.com
                Article
                10.3389/fnmol.2018.00072
                5845556
                46cb7721-715a-4192-bc73-af772e577636
                Copyright © 2018 Liu, Zhou, Peng, Su, Li, Xu, Tu, Tian, Yang, Wu, Mei and Gao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 November 2017
                : 20 February 2018
                Page count
                Figures: 9, Tables: 1, Equations: 0, References: 71, Pages: 16, Words: 0
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81771191
                Categories
                Neuroscience
                Original Research

                Neurosciences
                morphine tolerance,endoplasmic reticulum stress,unfolded protein response,binding immunoglobulin protein,activating transcription factor 6,protein kinase rna-like er kinase,inositol-requiring enzyme 1

                Comments

                Comment on this article