Cyclosporin A

Reference

• Endoplasmic reticulum vacuolation and unfolded protein response leading to paraptosis like cell death in cyclosporine A treated cancer cervix cells is mediated by cyclophilin B inhibition
  • B.M. Ram, G. Ramakrishna, Biochim. Biophys. Acta, 2014, 1843, 2497.


Anwendung
Lentivirus vector transduction enhancer
Cyclosporin A improves lentiviral vector transduction efficiency of human hematopoietic stem and progenitor cells.¹⁾ Combination of cyclosporine A with prostaglandin E2 further improves the efficiency.

References

• 1) Assessing the impact of cyclosporin A on lentiviral transduction and preservation of human hematopoietic stem cells in clinically relevant ex vivo gene therapy settings
• C. Petrillo, A. Calabria, F. Piras, A. Capotondo, G. Spinozzi, I. Cuccovillo, F. Benedicenti, L. Naldini, E. Montini, A. Biffi, B. Gentner, A. Kajaste-Rudnitski, Hum. Gene Ther. 2019, 30, 1133.


Anwendung
Cyclosporin A: A Calcineurin Inhibitor with Immunosuppressive Properties
Cyclosporin A (CsA) is a cyclic polypeptide immunosuppressant, and was initially isolated from the fungus Tolypocladium inflatum Gams in 1970. Cyclosporin A is practically insoluble in water, soluble in diethyl ether, and very soluble in methanol, ethanol and acetonitrile. Cyclosporin A inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that cyclosporin A is inactive by itself and requires binding to an intracellular protein, cyclophiline D (CypD), for activation in cells. A complex of CsA–CypD, calcium, calmodulin, and calcineurin (a calcium and calmodulin dependent protein phosphatase) is then formed and the phosphatase activity of calcineurin inhibited. This effect may prevent both T-lymphocyte signal transduction and IL-2 transcription. Tacrolimus (FK506) [M2258] is also inhibits calcineurin and is more potent than cyclosporin A. Cyclosporin A is mainly metabolized by cytochrome P 450 IIIA (CYP3A) subfamilies. (The product is for research purpose only.)

References

• Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
  • J. Liu, J. D. Farmer, W. S. Lane, J. Friedman, I. Weissman, S. L. Schreiber, Cell 1991, 66, 807.
• Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
  • N. A. Clipstone, G. R. Crabtree, Nature 1992, 357, 695.
• The mechanism of action of cyclosporin A and FK506
  • S. L. Schreiber, G. R. Crabtree, Immunol. Today 1992, 13, 136.
• Cyclosporin A, FK-506, and rapamycin: Pharmacologic probes of lymphocyte signal transduction
  • N. H. Sigal, F. J. Dumont, Annu. Rev. Immunol. 1992, 10, 519.
• Mechanisms of action of cyclosporine
  • S. Matsuda, S. Koyasu, Immunopharmacology 2000, 47, 119.
• Complex contribution of cyclophilin D to Ca²⁺-induced permeability transition in brain mitochondria, with relation to the bioenergetic state
  • J. Doczi, L. Turiák, S. Vajda, M. Mándi, B. Töröcsik, A. A. Gerencser, G. Kiss, C. Konràd, V. Adam-Vizi, C. Chinopoulos, J. Biol. Chem. 2011, 286, 6345.
• Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury
  • S. Y. Kim, M. S. Shim, K.-Y. Kim, R. N. Weinreb, L. A. Wheeler, W.-K. Ju, Cell Death Dis. 2014, 5, e1105.


PubMed Literatur