Distinctive lipid signatures of bronchial epithelial cells associated with cystic fibrosis drugs, including Trikafta.
JCI Insight
; 5(16)2020 08 20.
Article
em En
| MEDLINE
| ID: mdl-32673287
ABSTRACT
In recent years, a number of drugs have been approved for the treatment of cystic fibrosis (CF). Among them, newly released Trikafta, a combination of 3 drugs (VX-661/VX-445/VX-770), holds great promise to radically improve the quality of life for a large portion of patients with CF carrying 1 copy of F508del, the most frequent CF transmembrane conductance regulator (CFTR) mutation. Currently available disease-modifying CF drugs work by rescuing the function of the mutated CFTR anion channel. Recent research has shown that membrane lipids, and the cell lipidome in general, play a significant role in the mechanism of CFTR-defective trafficking and, on the other hand, its rescue. In this paper, by using untargeted lipidomics on CFBE41o- cells, we identified distinctive changes in the bronchial epithelial cell lipidome associated with treatment with Trikafta and other CF drugs. Particularly interesting was the reduction of levels of ceramide, a known molecular player in the induction of apoptosis, which appeared to be associated with a decrease in the susceptibility of cells to undergo apoptosis. This evidence could account for additional beneficial roles of the triple combination of drugs on CF phenotypes.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Piridinas
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Quinolinas
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Brônquios
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Fibrose Cística
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Células Epiteliais
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Benzodioxóis
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Metabolismo dos Lipídeos
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Aminofenóis
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Indóis
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article