ArticleAmerican journal of respiratory and critical care medicine2009
Bcl-2 suppresses sarcoplasmic/endoplasmic reticulum Ca2+-ATPase expression in cystic fibrosis airways: role in oxidant-mediated cell death.
Article in American journal of respiratory and critical care medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Reappraisal of the fundamental mechanisms of the sHA14-1 molecule as a Bcl-2/Bcl-XL ligand in the context of anticancer therapy: A cell biological study.Journal of biological methods · 2024Article
- The Impact of Air Pollution on the Course of Cystic Fibrosis: A Review.Frontiers in physiology · 2022Review
- Prolonged exposure to traffic-related particulate matter and gaseous pollutants implicate distinct molecular mechanisms of lung injury in rats.Particle and fibre toxicology · 2021Article
- Intracellular C3 Protects Human Airway Epithelial Cells from Stress-associated Cell Death.American journal of respiratory cell and molecular biology · 2019Article
- Acute pulmonary effects of aerosolized nicotine.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- SERCA directs cell migration and branching across species and germ layers.Biology open · 2017Article
- Transplantation of Airway Epithelial Stem/Progenitor Cells: A Future for Cell-Based Therapy.American journal of respiratory cell and molecular biology · 2017Article
- Review
- Sarcoendoplasmic reticulum Ca(2+) ATPase. A critical target in chlorine inhalation-induced cardiotoxicity.American journal of respiratory cell and molecular biology · 2015Article
- In vitro cell culture model for toxic inhaled chemical testing.Journal of visualized experiments : JoVE · 2014Article
- Human tracheobronchial basal cells. Normal versus remodeling/repairing phenotypes in vivo and in vitro.American journal of respiratory cell and molecular biology · 2013Article
- The selective BH4-domain biology of Bcl-2-family members: IP3Rs and beyond.Cellular and molecular life sciences : CMLS · 2013Review
- Molecular basis of asbestos-induced lung disease.Annual review of pathology · 2013Review
- Tissue factor signals airway epithelial basal cell survival via coagulation and protease-activated receptor isoforms 1 and 2.American journal of respiratory cell and molecular biology · 2013Article
- Acute inflammation induces insulin-like growth factor-1 to mediate Bcl-2 and Muc5ac expression in airway epithelial cells.American journal of respiratory cell and molecular biology · 2012Article
- Heat-shock proteins attenuate SERCA inactivation by the anti-apoptotic protein Bcl-2: possible implications for the ER Ca2+-mediated apoptosis.The Biochemical journal · 2012Article
- Interaction and localization of synthetic nanoparticles in healthy and cystic fibrosis airway epithelial cells: effect of ozone exposure.Journal of aerosol medicine and pulmonary drug delivery · 2012Article
- Apoptosis and the airway epithelium.Journal of allergy · 2011Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleModulation of the activity of sarcoendoplasmic reticulum calcium ATPase (SERCA) can profoundly affect Ca(2+) homeostasis. Although altered calcium homeostasis is a characteristic of cystic fibrosis (CF), the role of SERCA is unknown.
objectivesThis 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.
methodsLung 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
resultsSERCA2 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 (CFTR(inh)172), 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-alpha.
conclusionsReduced SERCA2 expression may alter calcium signaling and apoptosis in CF. These findings decrease the likelihood of therapeutic benefit of SERCA inhibition in CF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.