Evidence map›Paper›PMID 26149443›Full record

ArticleMolecular & cellular proteomics : MCP2015

Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis.

Steven D Stockton, Ivone Gomes, Tong Liu, Chandrakala Moraje, Lucia Hipólito, Matthew R Jones, Avi Ma'ayan, Jose A Morón, Hong Li, Lakshmi A Devi

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 17 citations in OpenAlex.

  1. tRNA epitranscriptomic alterations associated with opioid-induced reward-seeking and long-term opioid withdrawal in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  2. Article
  3. Role of the Ubiquitin System in Chronic Pain.Frontiers in molecular neuroscience · 2021
    Review
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Steven D StocktonFrom the ‡Department of Pharmacology and Systems Therapeutics, §Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029;
Ivone GomesFrom the ‡Department of Pharmacology and Systems Therapeutics.
Tong Liu¶Center for Advanced Proteomic Research and Department of Biochemistry and Molecular Biology, New Jersey Medical School Cancer Center, Rutgers University, Newark, New Jersey, 07103;
Chandrakala MorajeFrom the ‡Department of Pharmacology and Systems Therapeutics.
Lucia Hipólito‖Department of Anesthesiology, Columbia University Medical Center, New York, New York, 10027.
Matthew R JonesFrom the ‡Department of Pharmacology and Systems Therapeutics.
Avi Ma'ayanFrom the ‡Department of Pharmacology and Systems Therapeutics.
Jose A Morón‖Department of Anesthesiology, Columbia University Medical Center, New York, New York, 10027.
Hong Li¶Center for Advanced Proteomic Research and Department of Biochemistry and Molecular Biology, New Jersey Medical School Cancer Center, Rutgers University, Newark, New Jersey, 07103;
Lakshmi A DeviFrom the ‡Department of Pharmacology and Systems Therapeutics, §Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029; lakshmi.devi@mssm.edu.
Therapeutics Clinical Research · USColumbia University Irving Medical Center · USRutgers, The State University of New Jersey · USAllen Institute for Brain Science · USIcahn School of Medicine at Mount Sinai · US

Funding

Data Coordination and Integration Center for LINCS-BD2KU54HL127624 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MA'AYAN, AVI, SCHURER, STEPHAN C · 2014 to 2019
$23.5M
Rutgers Mass Spectrometry Core for Integrative Neuroscience ResearchP30NS046593 · NINDS · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI LOBEL, PETER · 2004 to 2018
$9.9M
Enzymes Involved in Neuropeptide Biosynthesis, Processing and RegulationR01NS026880 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DEVI, LAKSHMI A · 1994 to 2019
$6.5M
Post-translational Regulation of Opioid and Cannabinoid Receptors.R37DA008863 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DEVI, LAKSHMI A · 2012 to 2021
$4.6M
AMPA receptors: Common role in opiate withdrawal and pain sensitivityR01DA027460 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CARLTON, SUSAN M, MORON-CONCEPCION, JOSE A · 2010 to 2014
$2.8M
User Interface PortalU54CA189201 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DUDLEY, JOEL THOMAS, MA'AYAN, AVI · 2014 to 2017
$1.9M
Expression2Kinases: mRNA Profiling Linked to Multiple Upstream Regulatory LayersR01GM098316 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MA'AYAN, AVI · 2012 to 2015
$1.3M
POST-TRANSLATIONAL REGULATION OF OPIOID RECEPTORSK05DA019521 · NIDA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI DEVI, LAKSHMI A · 2005 to 2014
$1.2M
Role for delta opioid receptor in morphine tolerance during chronic painR21DA036826 · NIDA · WASHINGTON UNIVERSITY · PI CARLTON, SUSAN M, MORON-CONCEPCION, JOSE A · 2014 to 2015
$459k
ENZYMES INVOLVED IN DYNORPHIN BIOSYNTHESISR29NS026880 · NINDS · NEW YORK UNIVERSITY · PI DEVI, LAKSHMI A · 1989 to 1993
–
NCI NIH HHS U54 CA189201NCI NIH HHS U54CA189201NHGRI NIH HHS U54HG008230NHLBI NIH HHS U54 HL127624NIDA NIH HHS DA019521NIDA NIH HHS DA027460NIDA NIH HHS DA036826NIDA NIH HHS K05 DA019521NIDA NIH HHS R01 DA027460NIDA NIH HHS R21 DA036826NIDA NIH HHS R37 DA008863NIGMS NIH HHS R01 GM098316NIGMS NIH HHS R01GM098316NINDS NIH HHS NS026880NINDS NIH HHS NS046593NINDS NIH HHS P30 NS046593NINDS NIH HHS R01 NS026880
6 · The paper itself

Abstract

Despite its efficacy, the use of morphine for the treatment of chronic pain remains limited because of the rapid development of tolerance, dependence and ultimately addiction. These undesired effects are thought to be because of alterations in synaptic transmission and neuroplasticity within the reward circuitry including the striatum. In this study we used subcellular fractionation and quantitative proteomics combined with computational approaches to investigate the morphine-induced protein profile changes at the striatal postsynaptic density. Over 2,600 proteins were identified by mass spectrometry analysis of subcellular fractions enriched in postsynaptic density associated proteins from saline or morphine-treated striata. Among these, the levels of 34 proteins were differentially altered in response to morphine. These include proteins involved in G-protein coupled receptor signaling, regulation of transcription and translation, chaperones, and protein degradation pathways. The altered expression levels of several of these proteins was validated by Western blotting analysis. Using Genes2Fans software suite we connected the differentially expressed proteins with proteins identified within the known background protein-protein interaction network. This led to the generation of a network consisting of 116 proteins with 40 significant intermediates. To validate this, we confirmed the presence of three proteins predicted to be significant intermediates: caspase-3, receptor-interacting serine/threonine protein kinase 3 and NEDD4 (an E3-ubiquitin ligase identified as a neural precursor cell expressed developmentally down-regulated protein 4). Because this morphine-regulated network predicted alterations in proteasomal degradation, we examined the global ubiquitination state of postsynaptic density proteins and found it to be substantially altered. Together, these findings suggest a role for protein degradation and for the ubiquitin/proteasomal system in the etiology of opiate dependence and addiction.

Indexed as

Analgesics, OpioidAnimalsCaspase 3Corpus StriatumEndosomal Sorting Complexes Required for TransportMaleMorphineNedd4 Ubiquitin Protein LigasesNerve Tissue ProteinsProteolysisProteomicsRats, Sprague-DawleyReceptor-Interacting Protein Serine-Threonine KinasesSynaptic TransmissionUbiquitinationUbiquitin-Protein LigasesAnalgesics, OpioidCasp3 protein, ratCaspase 3Endosomal Sorting Complexes Required for TransportMorphineNEDD4L protein, ratNedd4 protein, ratNedd4 Ubiquitin Protein LigasesNerve Tissue Proteinspostsynaptic density proteinsReceptor-Interacting Protein Serine-Threonine KinasesUbiquitin-Protein Ligases

Identifiers

PMID26149443
PMCPMC4597137
OpenAlexW2158519248

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.