• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2019
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2019
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Defects in sarcolemma repair and skeletal muscle function after injury in a mouse model of Niemann-Pick type A/B disease

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Michailowsky, V.
    Li, H.
    Mittra, B.
    Date
    2019
    Journal
    Skeletal Muscle
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1186/s13395-018-0187-5
    Abstract
    Background: Niemann-Pick disease type A (NPDA), a disease caused by mutations in acid sphingomyelinase (ASM), involves severe neurodegeneration and early death. Intracellular lipid accumulation and plasma membrane alterations are implicated in the pathology. ASM is also linked to the mechanism of plasma membrane repair, so we investigated the impact of ASM deficiency in skeletal muscle, a tissue that undergoes frequent cycles of injury and repair in vivo. Methods: Utilizing the NPDA/B mouse model ASM -/- and wild type (WT) littermates, we performed excitation-contraction coupling/Ca 2+ mobilization and sarcolemma injury/repair assays with isolated flexor digitorum brevis fibers, proteomic analyses with quadriceps femoris, flexor digitorum brevis, and tibialis posterior muscle and in vivo tests of the contractile force (maximal isometric torque) of the quadriceps femoris muscle before and after eccentric contraction-induced muscle injury. Results: ASM -/- flexor digitorum brevis fibers showed impaired excitation-contraction coupling compared to WT, a defect expressed as reduced tetanic [Ca 2+ ] i in response to electrical stimulation and early failure in sustaining [Ca 2+ ] i during repeated tetanic contractions. When injured mechanically by needle passage, ASM -/- flexor digitorum brevis fibers showed susceptibility to injury similar to WT, but a reduced ability to reseal the sarcolemma. Proteomic analyses revealed changes in a small group of skeletal muscle proteins as a consequence of ASM deficiency, with downregulation of calsequestrin occurring in the three different muscles analyzed. In vivo, the loss in maximal isometric torque of WT quadriceps femoris was similar immediately after and 2 min after injury. The loss in ASM -/- mice immediately after injury was similar to WT, but was markedly larger at 2 min after injury. Conclusions: Skeletal muscle fibers from ASM -/- mice have an impairment in intracellular Ca 2+ handling that results in reduced Ca 2+ mobilization and a more rapid decline in peak Ca 2+ transients during repeated contraction-relaxation cycles. Isolated fibers show reduced ability to repair damage to the sarcolemma, and this is associated with an exaggerated deficit in force during recovery from an in vivo eccentric contraction-induced muscle injury. Our findings uncover the possibility that skeletal muscle functional defects may play a role in the pathology of NPDA/B disease. © 2019 The Author(s).
    Sponsors
    Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R21AR071011 (N.W.A.), and National Institutes of Health training grants T32 AR-007592 (S.I.) and T32AR056993 (D.A.G.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
    Keyword
    Acid sphingomyelinase
    Calcium
    Lysosome
    Plasma membrane repair
    Skeletal muscle
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059503390&doi=10.1186%2fs13395-018-0187-5&partnerID=40&md5=13c10d547cddc620c9c445b3407cb5c1; http://hdl.handle.net/10713/8658
    ae974a485f413a2113503eed53cd6c53
    10.1186/s13395-018-0187-5
    Scopus Count
    Collections
    UMB Open Access Articles 2019

    entitlement

    Related articles

    • Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients.
    • Authors: Hollak CE, de Sonnaville ES, Cassiman D, Linthorst GE, Groener JE, Morava E, Wevers RA, Mannens M, Aerts JM, Meersseman W, Akkerman E, Niezen-Koning KE, Mulder MF, Visser G, Wijburg FA, Lefeber D, Poorthuis BJ
    • Issue date: 2012 Nov
    • Progressive impairment of CaV1.1 function in the skeletal muscle of mice expressing a mutant type 1 Cu/Zn superoxide dismutase (G93A) linked to amyotrophic lateral sclerosis.
    • Authors: Beqollari D, Romberg CF, Dobrowolny G, Martini M, Voss AA, Musarò A, Bannister RA
    • Issue date: 2016
    • Contraction and intracellular Ca(2+) handling in isolated skeletal muscle of rats with congestive heart failure.
    • Authors: Lunde PK, Dahlstedt AJ, Bruton JD, Lännergren J, Thorén P, Sejersted OM, Westerblad H
    • Issue date: 2001 Jun 22
    • Types A and B Niemann-Pick Disease.
    • Authors: Schuchman EH, Wasserstein MP
    • Issue date: 2016 Jun
    • Types A and B Niemann-Pick disease.
    • Authors: Schuchman EH, Wasserstein MP
    • Issue date: 2015 Mar
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    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.