KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Pharmaceutical Chemistry
    • Pharmaceutical Chemistry Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Pharmaceutical Chemistry
    • Pharmaceutical Chemistry Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Bcl-2 Suppresses Sarcoplasmic/Endoplasmic Reticulum Ca21-ATPase Expression in Cystic Fibrosis Airways

    Thumbnail
    View/Open
    ZhaoL_AJRCCM_179(9)816.pdf (1.088Mb)
    Issue Date
    2009
    Author
    Ahmad, Shama
    Ahmad, Aftab
    Dremina, Elena S.
    Sharov, Victor S.
    Guo, Xiaoling
    Jones, Tara N.
    Loader, Joan E.
    Tatreau, Jason R.
    Perraud, Anne-Laure
    Schoneich, Christian
    Randell, Scott H.
    White, Carl W.
    Publisher
    Americal Thoracic Society
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
    Show full item record
    Abstract
    Rationale: Modulation of the activity of sarcoendoplasmic reticulum calcium ATPase (SERCA) can profoundly affect Ca21 homeostasis. Although altered calcium homeostasis is a characteristic of cystic fibrosis (CF), the role of SERCA is unknown. Objectives: This study provides a comprehensive investigation of expression and activity of SERCA in CF airway epithelium. A detailed study of the mechanisms underlying SERCA changes and its consequences was also undertaken. Methods: Lung tissue samples (bronchus and bronchiole) from subjects with and without CF were evaluated by immunohistochemistry. Protein and mRNA expression in primary non-CF and CF cells was determined by Western and Northern blots. Measurements and Main Results: SERCA2 expression was decreased in bronchial and bronchiolar epithelia of subjects with CF. SERCA2 expression in lysates of polarized tracheobronchial epithelial cells from subjects with CF was decreased by 67%as compared with those from subjects without CF. Several non-CF and CF airway epithelial cell lines were also probed. SERCA2 expression and activity were consistently decreased in CF cell lines. Adenoviral expression of mutant F508 cystic fibrosis transmembrane regulator gene (CFTR), inhibition of CFTR function pharmacologically (CFTRinh172), or stable expression of antisense oligonucleotides to inhibit CFTR expression caused decreased SERCA2 expression. In CF cells, SERCA2 interacted with Bcl-2, leading to its displacement from caveolae-related domains of endoplasmic reticulum membranes, as demonstrated in sucrose density gradient centrifugation and immunoprecipitation studies. Knockdown of SERCA2 using siRNA enhanced epithelial cell death due to ozone, hydrogen peroxide, and TNF-a. Conclusions: Reduced SERCA2 expression may alter calciumsignaling and apoptosis in CF. These findings decrease the likelihood oftherapeutic benefit of SERCA inhibition in CF.
    URI
    http://hdl.handle.net/1808/17569
    DOI
    https://doi.org/10.1164/rccm.200807-1104OC
    Collections
    • Pharmaceutical Chemistry Scholarly Works [336]
    Citation
    Shama Ahmad, Aftab Ahmad, Elena S. Dremina, Victor S. Sharov, Xiaoling Guo, Tara N. Jones, Joan E. Loader, Jason R. Tatreau, Anne-Laure Perraud, Christian Schöneich, Scott H. Randell, and Carl W. White "Bcl-2 Suppresses Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase Expression in Cystic Fibrosis Airways", American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 9 (2009), pp. 816-826. http;//dx.doi.org/10.1164/rccm.200807-1104OC

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps