en
Scientific article
English

Deep proteomics and phosphoproteomics reveal novel biological pathways perturbed by morphine, morphine-3-glucuronide and morphine-6-glucuronide in human astrocytes

Publication date2020
Abstract

Tolerance and hyperalgesia associated with chronic exposure to morphine are major limitations in the clinical management of chronic pain. At a cellular level, neuronal signaling can in part account for these undesired side effects, but unknown mechanisms mediated by central nervous system glial cells are likely also involved. Here we applied data-independent acquisition mass spectrometry to perform a deep proteome and phosphoproteome analysis of how human astrocytes responds to opioid stimulation. We unveil time- and dose-dependent effects induced by morphine and its major active metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide that converging on activation of mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. We also find that especially longer exposure to M3G leads to significant dysregulation of biological pathways linked to extracellular matrix organization, antigen presentation, cell adhesion, and glutamate homeostasis, which are crucial for neuron- and leukocyte-astrocyte interactions.

Keywords
  • Astrocytes
  • Data-independent mass spectrometry
  • DIA MS
  • M3G
  • M6G
  • Morphine
  • Opioids
  • Phosphorylation
  • Proteomics
Funding
  • Autre - Swiss Centre for Applied Human Toxicology
Citation (ISO format)
DOZIO, Vito et al. Deep proteomics and phosphoproteomics reveal novel biological pathways perturbed by morphine, morphine-3-glucuronide and morphine-6-glucuronide in human astrocytes. In: Journal of Neuroscience Research, 2020. doi: 10.1002/jnr.24731
Main files (1)
Article (Published version)
accessLevelRestricted
Secondary files (1)
Identifiers
ISSN of the journal0360-4012
243views
2downloads

Technical informations

Creation11/12/2020 1:32:00 PM
First validation11/12/2020 1:32:00 PM
Update time03/16/2023 12:08:44 AM
Status update03/16/2023 12:08:44 AM
Last indexation05/06/2024 6:43:51 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack