Cyclosporin H is a hydroxylated metabolite of Cyclosporin A. Cyclosporin H (M-1) and other cyclosporin metabolites have been found to have lower (<10%) immunosuppressant activity than cyclosporin A. Cyclosporin H has been found to be a potent inhibitor of superoxide anion (O2-) formation by FMLP (N-Formylmethionyl-leucyl-phenylalanine) in human neutrophils.
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|Mechanism of Action|
Cyclosporin H (and other cyclosporin A metabolites) have lower immunosuppressant activity but most likely operate under the same mechanism as cyclosporin A (CsA) described below.Cyclosporin B (and other cyclosporin A metabolites) have lower immunosuppressive activity but likely operate under the same mechanism as cyclosporin A described below. After entering a T-cell, Cyclosporin A associates with the cytosolic protein cyclophilin which helps in protein folding. Cyclosporin A binds to cyclophilins and this complex binds another cytosolic protein phosphatase called Calcineurin (protein phosphatase 2B) that dephosphorylates a transcription factor (nuclear factor of activated T-cells, or NF-AT) needed for expression of interleukin 2 (IL-2.). It also blocks the pathway to nitric oxide synthesis via tumor necrosis factor (TNFa) and Interleukin 1a.
|Eukaryotic Cell Culture Applications||Cyclosporins have used as tools to study complex biological networks and pathways, involving protein function, and protein-protein interactions.|
|Cancer Applications||Cyclosporin’s immunosuppressive properties and potential toxicity can be studied during in vitro assays. Other metabolites of Cyclosporin A (AM1, AM1c, DihydroAM1, AM19, and AM4N) can also be studied (Vollenbroeker B et al, 2005).|
|References||Anderson MA and Gusella JF (1984) Use of Cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro 20(11):856-858. PMID 6519667 |
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