Overview
- Fruman, D.A. et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3686.
- Cardenas, M.E. et al. (1998) Trends Biotechnol. 16, 427.
- Kino, T. et al. (1987) J. Antibiot. 40, 1249.
Alomone Labs FK-506 inhibits the anti-adipogenic effect of calcineurin in 3T3-L1 cells.Cells were induce to undergo differentiation with 1 µg/ml insulin for 4 days (A, B and C). The cells were treated for the first 4 days of differentiation with 1 µM Ionomycin (#I-700), (B and C) in the presence of 5 ng/ml (C) or absence (A and B) of FK-506 (#F-900). After 10 days, the cells were stained with Oil red O and visualized with light microscopy.
FK 506 (Tacrolimus), a macrolide compound isolated from Streptomyces tsukubaensis, is a potent immunosuppressive compound that inhibits T-cell activation and is an inhibitor of fungal growth (10 to 100 times more potent than Cyclosporin A).1-3 FK-506 binds and inhibits, in vitro, the activity of immunophilin proteins known as FK 506-binding protein (FKBP), in a variety of organisms, ranging from yeast to humans.4-8
Immunosuppression activity of FK-506 seems to be due to FK-506/FKBP complex that inhibits the heterodimeric Ca2+/calmodulin-dependent phosphatase Calcineurin. This, in turn, prevents the Calcineurin-dependent activation of interleukin-2 transcription and T-cell proliferation.9-12 FK-506 inhibits FKBP activities, increases sarcoplasmic reticulum Ca2+ release and decreases the ability of Na+/Ca2+ exchange to extrude Ca2+ from the cell.13
