Cyclosporin A

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Cyclosporin A

Description

Cyclosporin A (CsA) is a cyclic undecapeptide from an extract of soil fungi that binds the cyclophilin D and thus preventing the formation of the mitochondrial permeability transition pore. The interaction of CsA with the cyclophilin D is phosphate mediated but the full mechanism of interaction is not well understood. For example, the deficiency of cyclophilin D in KO models does not prevent mitochondria from permeability transition and from CsA inhibition. Moreover, it is also a is a calcineurin inhibitor and potent immunosuppressive agent used largely as a means of prophylaxis against cellular rejection after solid organ transplantation.

Abbreviation: CsA

Application in HRR

CsA: Cyclosporin A (Antibiotic S 7481F1; C62H111N11O12), Sigma-Aldrich: 30024, store at 2-8 °C, CAS: 59865-13-3, M = 1202.61 g·mol-1
Hazard statements: H302, H350, H360FD; harmful if swallowed, may cause cancer, may damage fertility, may damage the unborn child.


Preparation of 400 µM stock solution (dissolved in ethanol abs.)
  1. Weigh 1 mg of CsA and dissolve in 2.11 ml of ethanol abs..
  2. Divide in aliquots.
  3. Store frozen at -20 °C.


» O2k manual titrations MiPNet09.12 O2k-Titrations
  • Titration volume: 5 µL using a 10 µL syringe (2 mL O2k-chamber).
  • Final concentration: 1 µM.


Even if 1 µM is recommended as the working concentration in most of the publications it is highly relevant to test the optimal concentration for your research model.


Inhibition of PTP by CsA

  • Gainutdinov T, Molkentin JD, Siemen D, Ziemer M, Debska-Vielhaber G, Vielhaber S, Gizatullina Z, Orynbayeva Z, Gellerich FN (2015) Knockout of cyclophilin D in Ppif-/- mice increases stability of brain mitochondria against Ca2+ stress. Arch Biochm Biophys 579:40–46.
  • Briston T, Roberts M, Lewis S, Powney B, Staddon JM, Szabadkai G, Duchen MR (2017) Mitochondrial permeability transition pore: sensitivity to opening and mechanistic dependence on substrate availability. Scientific reports 7: 10492.






MitoPedia topics: Inhibitor