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Current Topics in Pharmacology   Volumes    Volume 4 
Cyclosporin, from clinical to basic research
Edmundo Chávez, Cecilia Zazueta
Pages: 183 - 192
Number of pages: 10
Current Topics in Pharmacology
Volume 4 

Copyright © 1998 Research Trends. All rights reserved

The immunosuppressant drug cyclosporin A was first used in the clinic in 1978 in a kidney transplant surgery to prevent organ rejection. Its immunosuppressive activity is due to a Ca2+ -calmodulin-dependent binding of the cyclosporine-cyclophilin complex to calcineurin phosphatase. The inhibition of the calcineurin blocks the transcription of nuclear genes that depends on the nuclear factor for activation of T cells (NFTA) and prevents the production of cytokines, including IL-2. Recently, cyclosporin A has been used as a useful tool to protect membrane mitochondria against the deleterious effect of Ca2+ on membrane selective permeability. The closure of the non-specific pore by cyclosporin A appears to be related with the inhibition of the activity of mitochondrial cyclophilin, a peptidyl-prolil-cis-trans isomerase with a Ki of 2.5mM. Plausibly, the beneficial effect of cyclosporin on mitochondrial permeability transition underlies in the protective role of the drug on cell apoptosis and cell damage by ischemia-reperfusion.
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