Metabolic interactions between cysteamine and epigallocatechin gallate |
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Authors: | Valentina Izzo Federico Pietrocola Valentina Sica Sylvère Durand Sylvie Lachkar David Enot |
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Affiliation: | 1. Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France;2. Université Paris Descartes, Sorbonne Paris Cité, Paris, France;3. Université Pierre et Marie Curie, Paris, France;4. Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France;5. Université Paris Sud, Faculté de Médecine, Kremlin Bicêtre, France |
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Abstract: | Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the 2 components alone. In a cell-free system, protein cross-linking activity of EGCG was suppressed by cysteamine. Finally, EGCG was able to enhance the conversion of cysteamine into taurine in metabolic flux experiments. Altogether, these results indicate that multiple pharmacological interactions occur between cysteamine and EGCG, suggesting that they contribute to the unique synergy of both agents in restoring the function of mutated CFTRΔF508. |
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Keywords: | acetylation cysteamine cystic fibrosis EP300 epigallocatechin gallate metabolic flux metabolic profiling |
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