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.
Alomone Labs Cyclosporin A 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-D) in the presence of 10 ng/ml (C) or 50 ng/ml (D) Cyclosporin A (#C-900). After 10 days, the cells were stained with Oil red O and visualized with light microscopy.
Cyclosporin A is a hydrophobic, cyclic peptide isolated from Tolypocladium inflatum and is a potent immunosuppressant and antifungal compound. It acts via its ability to bind a family of intracellular proteins, the cyclophilins (intracellular peptidyl-prolyl cis-trans isomerases), which are abundant, ubiquitous, highly conserved, and found in multiple forms in different intracellular compartments.1 In yeast, Cyclophilin A, an 18-kDa cytoplasmic protein, mediates Cyclosporin A actions.2,3
The immunosuppressive action of Cyclosporin A is mediated by the Cyclosporin A-Cyclophilin complex that specifically inhibits the Ca2+/calmodulin-dependent serine-threonine-protein phosphatase-2B (Calcineurin).4-10 This, in turn, inhibits Calcineurin and promotes dephosphorylation of transcription factor NF-AT and T cell activation.11-14 In vivo, Cyclosporin A-induced hypertension involves the attenuation of endothelium-derived NO production through the inhibition of Calcineurin-sensitive pathways regulating eNOS dephosphorylation.15
Cyclosporin A has been shown to alter cell proliferation in different systems. For hematopoietic progenitor stem and progenitor cells, smooth muscle cells, and hepatocytes, it serves as an inducer of cell proliferation or as a tumor promoting effector.16-18 On the other hand, growth of interleukin-3-dependent mast cells, human lung-cancer cells, tubular kidney cells, cultured pituitary cells, T-cells, and keratinocytes were inhibited by Cyclosporin A.19-21 Moreover, Cyclosporin A has been observed in vitro and in vivo as an antimalarial agent, but the exact mechanism is not yet clear.22
