| Literature DB >> 28059601 |
Valentina Izzo1,2,3,4, Federico Pietrocola1,2,3,4, Valentina Sica1,2,3,4,5, Sylvère Durand1,2,3,4, Sylvie Lachkar1,2,3,4, David Enot1,2,3,4, José Manuel Bravo-San Pedro1,2,3,4, Alexis Chery1,2,3,4, Speranza Esposito6, Valeria Raia7, Luigi Maiuri6,8, Maria Chiara Maiuri1,2,3,4, Guido Kroemer1,2,3,4,9,10.
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.Entities:
Keywords: EP300; acetylation; cysteamine; cystic fibrosis; epigallocatechin gallate; metabolic flux; metabolic profiling
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Year: 2017 PMID： 28059601 PMCID： PMC5323035 DOI： 10.1080/15384101.2016.1249550
Source DB: PubMed Journal: Cell Cycle ISSN： 1551-4005 Impact factor: 4.534