Identification of several cyclosporine binding proteins in lymphoid and non-lymphoid cells in vivo

Brian M.J. Foxwell, Gaetane Woerly, Holger Husi, Andrew Mackie, Valerie F.J. Quesniaux, Peter C. Hiestand, Roland M. Wenger, Bernhard Ryffel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The immunosuppressant cyclosporine A (CSA) has been shown to bind to the ubiquitous cellular protein, cyclophilin, and to inhibit its rotamase activity. In the present study, 3H-cyclosporine diazirine analogue was used to photolabel viable human cells of lymphoid and fibroblast origin in order to identify the intracellular targets for the drug. While cyclophilin was strongly labeled in situ, additional minor cyclosporine-protein complexes of 25, 40, 46 and 60 kDa were identified in the T cell leukemia cell line Jurkat. These proteins bound specifically, since only active CSA but not inactive CSH or FK506 competed for binding. Photolabeling of MRC5 cells, a CSA resistant human fibroblast cell line, revealed a 25 kDa complex as the major product, while the 46 and 60 kDa bands were not detectable and cyclophilin labeling was only faint, even though both MRC5 and Jurkat cells contain similar cyclophilin concentrations. Thus, our data suggest that the intracellular targets of CSA and/or the accessibility to cyclophilin varies considerably in drug sensitive and resistant cell types, which may contribute to explaining the lymphocyte selectivity of the drug.
Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalBiochimica et Biophysica Acta: Molecular Basis of Disease
Volume1138
Issue number2
DOIs
Publication statusPublished - 1 Feb 1992

Fingerprint Dive into the research topics of 'Identification of several cyclosporine binding proteins in lymphoid and non-lymphoid cells in vivo'. Together they form a unique fingerprint.

Cite this