ArticleThe Journal of biological chemistry2012
Arsenic promotes ubiquitinylation and lysosomal degradation of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in human airway epithelial cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- A Meta-analysis of Arsenic Exposure and Lung Function: Is There Evidence of Restrictive or Obstructive Lung Disease?Current environmental health reports · 2018Pooled it
- Article
- Environmental-level exposure to metals and metal-mixtures associated with spirometry-defined lung disease in American Indian adults: Evidence from the Strong Heart Study.Environmental research · 2022Article
- Ubiquitin-specific peptidase 10, a deubiquitinating enzyme: Assessing its role in tumor prognosis and immune response.Frontiers in oncology · 2022Review
- Inferred inactivation of the Cftr gene in the duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its potential role in Cr(VI)-induced carcinogenesis of the small intestines.Toxicology and applied pharmacology · 2021Article
- Lung function of primary cooks using LPG or biomass and the effect of particulate matter on airway epithelial barrier integrity.Environmental research · 2020Article
- Evaluation of secondhand smoke effects on CFTR function in vivo.Respiratory research · 2020Article
- Rice Consumption and Subclinical Lung Disease in US Adults: Observational Evidence From the Multi-Ethnic Study of Atherosclerosis.American journal of epidemiology · 2019Article
- CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine.Frontiers in pharmacology · 2019Review
- Peripheral Protein Quality Control as a Novel Drug Target for CFTR Stabilizer.Frontiers in pharmacology · 2018Review
- The impact of BMI on non-malignant respiratory symptoms and lung function in arsenic exposed adults of Northern Chile.Environmental research · 2017Article
- Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice.Environmental health perspectives · 2017Article
- Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells.Toxicology and applied pharmacology · 2017Article
- Effects ofAmerican journal of physiology. Cell physiology · 2017Review
- Does arsenic increase the risk of neural tube defects among a highly exposed population? A new case-control study in Bangladesh.Birth defects research · 2017Article
- Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance.Clinics in chest medicine · 2016Review
- Advancing toxicology research using in vivo high throughput toxicology with small fish models.ALTEX · 2016Article
- Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR.Biochimica et biophysica acta · 2015Article
- Elevated sweat chloride levels due to arsenic toxicity.The New England journal of medicine · 2015Article
- Testing multiple hypotheses through IMP weighted FDR based on a genetic functional network with application to a new zebrafish transcriptome study.BioData mining · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Arsenic exposure significantly increases respiratory bacterial infections and reduces the ability of the innate immune system to eliminate bacterial infections. Recently, we observed in the gill of killifish, an environmental model organism, that arsenic exposure induced the ubiquitinylation and degradation of cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is essential for the mucociliary clearance of respiratory pathogens in humans. Accordingly, in this study, we tested the hypothesis that low dose arsenic exposure reduces the abundance and function of CFTR in human airway epithelial cells. Arsenic induced a time- and dose-dependent increase in multiubiquitinylated CFTR, which led to its lysosomal degradation, and a decrease in CFTR-mediated chloride secretion. Although arsenic had no effect on the abundance or activity of USP10, a deubiquitinylating enzyme, siRNA-mediated knockdown of c-Cbl, an E3 ubiquitin ligase, abolished the arsenic-stimulated degradation of CFTR. Arsenic enhanced the degradation of CFTR by increasing phosphorylated c-Cbl, which increased its interaction with CFTR, and subsequent ubiquitinylation of CFTR. Because epidemiological studies have shown that arsenic increases the incidence of respiratory infections, this study suggests that one potential mechanism of this effect involves arsenic-induced ubiquitinylation and degradation of CFTR, which decreases chloride secretion and airway surface liquid volume, effects that would be proposed to reduce mucociliary clearance of respiratory pathogens.
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