• Login
    View Item 
    •   Home
    • UA Faculty Research
    • UA Faculty Publications
    • View Item
    •   Home
    • UA Faculty Research
    • UA Faculty Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Heat-shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK mitogen-activated protein kinase (MAPK) mechanism in mouse brain

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    J.Biol.Chem.-2017-Lei-10414-28.pdf
    Size:
    2.871Mb
    Format:
    PDF
    Description:
    Final Accepted Manuscript
    Download
    Author
    Lei, Wei
    Mullen, Nathan
    McCarthy, Sarah
    Brann, Courtney
    Richard, Philomena
    Cormier, James
    Edwards, Katie
    Bilsky, Edward J.
    Streicher, John M.
    Affiliation
    Univ Arizona, Coll Med, Dept Pharmacol
    Issue Date
    2017-06-23
    
    Metadata
    Show full item record
    Publisher
    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
    Citation
    Lei W, Mullen N, McCarthy S, Brann C, Richard P, Cormier J, Edwards K, Bilsky EJ, and Streicher JM. 2017. Heat Shock Protein 90 (Hsp90) Promotes Opioid-Induced Anti-Nociception by an ERK Mitogen Activated Protein Kinase (MAPK) Mechanism in Mouse Brain. Journal of Biological Chemistry. 292(25):10414-10428. doi:10.1074/jbc.M116.769489
    Journal
    Journal of Biological Chemistry
    Rights
    © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Recent advances in developing opioid treatments for pain with reduced side effects have focused on the signaling cascades of the μ-opioid receptor (MOR). However, few such signaling targets have been identified for exploitation. To address this need, we explored the role of heat-shock protein 90 (Hsp90) in opioid-induced MOR signaling and pain, which has only been studied in four previous articles. First, in four cell models of MOR signaling, we found that Hsp90 inhibition for 24 h with the inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) had different effects on protein expression and opioid signaling in each line, suggesting that cell models may not be reliable for predicting pharmacology with this protein. We thus developed an in vivo model using CD-1 mice with an intracerebroventricular injection of 17-AAG for 24 h. We found that Hsp90 inhibition strongly blocked morphine-induced anti-nociception in models of post-surgical and HIV neuropathic pain but only slightly blocked anti-nociception in a naive tail-flick model, while enhancing morphine-induced precipitated withdrawal. Seeking a mechanism for these changes, we found that Hsp90 inhibition blocks ERK MAPK activation in the periaqueductal gray and caudal brain stem. We tested these signaling changes by inhibiting ERK in the above-mentioned pain models and found that ERK inhibition could account for all of the changes in anti-nociception induced by Hsp90 inhibition. Taken together, these findings suggest that Hsp90 promotes opioid-induced anti-nociception by an ERK mechanism in mouse brain and that Hsp90 could be a future target for improving the therapeutic index of opioid drugs.
    Note
    12 month embargo; published online: 27 April 2017
    ISSN
    0021-9258
    1083-351X
    DOI
    10.1074/jbc.M116.769489
    Version
    Final accepted manuscript
    Additional Links
    http://www.jbc.org/lookup/doi/10.1074/jbc.M116.769489
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M116.769489
    Scopus Count
    Collections
    UA Faculty Publications

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.