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Effects of taurine and other amino acids on the phenotype of F508‐CFTR cells
Author(s) -
Rotoli Bianca Maria,
Bianchi Massimiliano,
Dall'Asta Valeria,
Bussolati Ovidio
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1039-d
Subject(s) - taurine , amino acid , osmolyte , intracellular , biochemistry , efflux , alanine , chemistry , sarcosine , glycine , cotransporter , glutamine , proline , microbiology and biotechnology , biology , sodium , organic chemistry
When employed at high concentration (300 mM) or together with other organic osmolytes, taurine promotes ΔF508‐CFTR protein folding and CF phenotype rescue. To characterize this effect, we have compared taurine with other amino acids and amino acid derivatives and correlated the efficacy as chemical chaperone with the intracellular concentration of the various compounds. C127 cells transfected with F508 CF cDNA were treated for 24h with 10 mM of α‐neutral amino acids, substrates of the concentrative transporter SNAT2 (glutamine, proline, glycine, alanine, MeAIB), or β‐amino acids substrates of the taurine cotransporter TAUT (hypotaurine, β‐alanine, aminoiminomethyl‐β‐alanine). The corrective effect of the various compounds on CF phenotype was evaluated from the rescue of cAMP‐dependent 36 Cl‐ efflux. Taurine‐treated ΔF508‐CFTR cells exhibited a cAMP‐dependent 36 Cl‐ efflux (comparable to that observed after a 2‐day‐incubation at 27 °C, a condition known to induce the membrane targeting of the mutant CFTR), an intracellular taurine concentration of 45 mM, and a 15% decrease in cell volume. The other tested compounds had a smaller (MeAIB, Gln, Gly) or a null effect on CF phenotype, although their intracellular concentrations were similar or even higher than that attained by taurine. These results indicate that taurine alone can correct CF phenotype at the cell level and that this effect is not simply attributable to an enhanced availability of the amino acid in the intracellular compartment. Supported by “Fondazione per la ricerca sulla fibrosi cistica”, Verona, Italy (Grant FFC#3/2004).