dc.contributor.author | Ahmad, Shama | |
dc.contributor.author | Ahmad, Aftab | |
dc.contributor.author | Dremina, Elena S. | |
dc.contributor.author | Sharov, Victor S. | |
dc.contributor.author | Guo, Xiaoling | |
dc.contributor.author | Jones, Tara N. | |
dc.contributor.author | Loader, Joan E. | |
dc.contributor.author | Tatreau, Jason R. | |
dc.contributor.author | Perraud, Anne-Laure | |
dc.contributor.author | Schoneich, Christian | |
dc.contributor.author | Randell, Scott H. | |
dc.contributor.author | White, Carl W. | |
dc.date.accessioned | 2015-05-04T18:33:34Z | |
dc.date.available | 2015-05-04T18:33:34Z | |
dc.date.issued | 2009 | |
dc.identifier.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 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17569 | |
dc.description.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. | en_US |
dc.description.sponsorship | The authors thank Leslie Fulcher for expert technical advice on primary airway cell culture; Dr. A.S. Verkman, University of California, San Francisco, CA, for providing the CFTRinh172; Dr. P.B. Davis, Case Western Reserve University Cleveland, OH, for the CFTR-S and CFTR-AS expressing 16HBEo- cells; Barbara K. Schneider for assistance with immunofluorescence experiments and Stacy Miller for assistance with the siRNA experiments; Tara Hendry-Hofer for assistance in the quantitation of the IHCs; and Starsa Duskin for assistance with toxicity determinations. | en_US |
dc.publisher | Americal Thoracic Society | en_US |
dc.title | Bcl-2 Suppresses Sarcoplasmic/Endoplasmic Reticulum Ca21-ATPase Expression in Cystic Fibrosis Airways | en_US |
dc.type | Article | |
kusw.kuauthor | Dremina, Elena S. | |
kusw.kuauthor | Sharov, Victor S. | |
kusw.kuauthor | Schoneich, Christian | |
kusw.kudepartment | Department of Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1164/rccm.200807-1104OC | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |