1. Redox regulation of cyclophilin A by glutathionylation
- Author
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Simona Casagrande, Rossella Tonelli, Maddalena Fratelli, Luca Mollica, Barbara Sherry, Emanuele Bellacchio, Mario Salmona, Ivano Eberini, Wei Wei Dai, Emiliano Biasini, Manuela Basso, Tania Massignan, Elisabetta Gianazza, Pietro Ghezzi, and Valentina Bonetto
- Subjects
Proteomics ,T-Lymphocytes ,Cypa ,Lymphocyte Activation ,Biochemistry ,Cyclophilin A ,Cyclosporin a ,Humans ,Electrophoresis, Gel, Two-Dimensional ,Cysteine ,Molecular Biology ,Peptidylprolyl isomerase ,biology ,Circular Dichroism ,Computational Biology ,biology.organism_classification ,Glutathione ,Recombinant Proteins ,Cell biology ,Cytosol ,Cis-trans-Isomerases ,Mitogen-activated protein kinase ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,biology.protein ,Oxidation-Reduction - Abstract
Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity.
- Published
- 2005