Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis.
Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3197197?pdf=render |
| _version_ | 1811282581696544768 |
|---|---|
| author | Noura S Abul-Husn Suresh P Annangudi Avi Ma'ayan Dinah L Ramos-Ortolaza Steven D Stockton Ivone Gomes Jonathan V Sweedler Lakshmi A Devi |
| author_facet | Noura S Abul-Husn Suresh P Annangudi Avi Ma'ayan Dinah L Ramos-Ortolaza Steven D Stockton Ivone Gomes Jonathan V Sweedler Lakshmi A Devi |
| author_sort | Noura S Abul-Husn |
| collection | DOAJ |
| description | Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory-based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine-induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence. |
| first_indexed | 2024-04-13T01:55:09Z |
| format | Article |
| id | doaj.art-89107089705243909dd4da0e1e7168a3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T01:55:09Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-89107089705243909dd4da0e1e7168a32022-12-22T03:07:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01610e2553510.1371/journal.pone.0025535Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis.Noura S Abul-HusnSuresh P AnnangudiAvi Ma'ayanDinah L Ramos-OrtolazaSteven D StocktonIvone GomesJonathan V SweedlerLakshmi A DeviOpiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory-based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine-induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence.http://europepmc.org/articles/PMC3197197?pdf=render |
| spellingShingle | Noura S Abul-Husn Suresh P Annangudi Avi Ma'ayan Dinah L Ramos-Ortolaza Steven D Stockton Ivone Gomes Jonathan V Sweedler Lakshmi A Devi Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. PLoS ONE |
| title | Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. |
| title_full | Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. |
| title_fullStr | Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. |
| title_full_unstemmed | Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. |
| title_short | Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. |
| title_sort | chronic morphine alters the presynaptic protein profile identification of novel molecular targets using proteomics and network analysis |
| url | http://europepmc.org/articles/PMC3197197?pdf=render |
| work_keys_str_mv | AT nourasabulhusn chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT sureshpannangudi chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT avimaayan chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT dinahlramosortolaza chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT stevendstockton chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT ivonegomes chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT jonathanvsweedler chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis AT lakshmiadevi chronicmorphinealtersthepresynapticproteinprofileidentificationofnovelmoleculartargetsusingproteomicsandnetworkanalysis |