A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA
| Autor: | Joanne E. Cluette-Brown, Waddah Katrangi, M. Rabie Al-Turkmani, Michael Laposata, Ragheed Alturkmani, Charlotte Andersson, Steven D. Freedman |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Cystic Fibrosis Docosahexaenoic Acids Linoleic acid Respiratory Mucosa QD415-436 Biology Biochemistry Linoleic Acid chemistry.chemical_compound Endocrinology Downregulation and upregulation Internal medicine Sense (molecular biology) arachidonic acid medicine Humans lipid classes Cells Cultured phospholipids chemistry.chemical_classification Wild type Fatty acid Cell Biology Metabolism docosahexaenoic acid chemistry n-6 pathway Docosahexaenoic acid lipids (amino acids peptides and proteins) Arachidonic acid Research Article fatty acid alterations |
| Zdroj: | Journal of Lipid Research, Vol 49, Iss 9, Pp 1946-1954 (2008) |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.m800035-jlr200 |
| Popis: | Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation. |
| Databáze: | OpenAIRE |
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