1. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.
- Author
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Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glöckner-Pagel J, Canny S, Du K, Lukacs GL, and Caplan MJ
- Subjects
- Animals, Calcium metabolism, Calnexin metabolism, Cell Line, Cricetinae, Curcumin administration & dosage, Curcumin therapeutic use, Cystic Fibrosis genetics, Cystic Fibrosis physiopathology, Cystic Fibrosis Transmembrane Conductance Regulator chemistry, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Electrolytes pharmacology, Gene Targeting, Glycosylation, Humans, Intestinal Mucosa drug effects, Intestinal Mucosa physiology, Intestinal Obstruction prevention & control, Isoproterenol pharmacology, Membrane Potentials drug effects, Mice, Mice, Knockout, Mutation, Nasal Mucosa physiology, Polyethylene Glycols pharmacology, Protein Folding, Rectum, Transfection, Cell Membrane metabolism, Curcumin pharmacology, Cystic Fibrosis drug therapy, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Endoplasmic Reticulum metabolism, Nasal Mucosa drug effects
- Abstract
Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.
- Published
- 2004
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