Cystic fibrosis (CF) is a severely life-shortening genetic disease resulting from mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). Impaired bicarbonate secretion is a key component of CF-related pancreatic disease, but the role of impaired bicarbonate secretion in CF lung disease is less well understood. The submucosal glands of the conducting airways produce and secrete a complex airway surface liquid that lines the airway epithelium and plays a significant role in mucociliary clearance. The serous cell is the predominant cell type of the submucosal gland and a predominant site of CFTR expression. Calu-3 cells are a model of airway submucosal gland serous cells that demonstrates vectorial bicarbonate secretion in response to elevations in cAMP. Based on previously published measurements of unidirectional ion flux, pharmacological inhibition of short-circuit current and ion substitution studies, one can hypothesize the existence of an electrogenic sodium bicarbonate cotransporter (NBC) in the basolateral membrane of Calu-3 cells that mediates bicarbonate entry from the interstitium. To test this hypothesis, we performed reverse-transcriptase PCR, western blotting, and surface biotinylation to identify and localize electrogenic NBCs in Calu-3 cells. Our data demonstrate that both pNBC1 and NBC4 mRNAs can be identified and that their protein products are expressed at the basolateral membrane of polarized Calu-3 cells. These data suggest that these transporters contribute to regulated bicarbonate secretion across Calu-3 cells and perhaps human airway submucosal glands.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bbadis.2006.06.005 | DOI Listing |
J Nat Prod
January 2025
Department of Natural Products, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar 382355, Gujarat, India.
Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.
View Article and Find Full Text PDFInt J Health Sci (Qassim)
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia.
Objective: Dasatinib (DTB) is a second-generation tyrosine kinase inhibitor that was found it could help with lung cancer treatment. However, DTB has low aqueous solubility and poor bioavailability due to its incomplete absorption and high first-pass effect. The objective of this study was to improve DTB's solubility, delivery, and efficacy as a potential lung cancer treatment by developing an inhalable DTB-nanoemulsion (DNE) formulation.
View Article and Find Full Text PDFEnviron Res
January 2025
Joint Mass Spectrometry Center (JMSC) at Comprehensive Molecular Analytics (CMA), Helmholtz Zentrum München, Munich, 85764, Germany; Joint Mass Spectrometry Center (JMSC) at Analytical Chemistry, Institute of Chemistry, University of Rostock, Rostock, 18051, Germany.
Air pollution significantly contributes to the global burden of respiratory and cardiovascular diseases. While single source/compound studies dominate current research, long-term, multi-pollutant studies are crucial to understanding the health impacts of environmental aerosols. Our study aimed to use the first air-liquid interface (ALI) aerosol exposure system adapted for long-term in vitro exposures for ambient air in vitro exposure.
View Article and Find Full Text PDFZhongguo Fei Ai Za Zhi
October 2024
Medical Laboratory Center, the Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830011, China.
Phytomedicine
November 2024
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. Electronic address:
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!