Cyclosporin A: Difference between revisions

Latest revision as of 11:04, 14 June 2022

high-resolution terminology - matching measurements at high-resolution

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.)

Weigh 1 mg of CsA and dissolve in 2.11 ml of ethanol abs..
Divide in aliquots.
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 mtPTP 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

@@ Line 6: / Line 6: @@
 __TOC__
 == Application in [[HRR]] ==
+{{Chemical_description
+|abbr=CsA
+|trivial name=Cyclosporin A
+|complete name=Antibiotic S 7481F1
+|chem formula=C<sub>62</sub>H<sub>111</sub>N<sub>11</sub>O<sub>12</sub>
-::::'''CsA:Cyclosporin A''' (C<sub>62</sub>H<sub>111</sub>N<sub>11</sub>O<sub>12</sub>); Sigma 30024, 25 mg, store commercial stock at 	2-8°C; FW = 1202.61 g/mol (≥ 95%).
+|molar mass=1202.61
+|vendor=Sigma-Aldrich
+|product number=30024
+|store at=2-8 °C
+|sensitivity=
+|cas=59865-13-3
+|h statements=H302, H350, H360FD
+|h info=harmful if swallowed, may cause cancer, may damage fertility, may damage the unborn child.
+}}<!--:::'''CsA:Cyclosporin A''' (C<sub>62</sub>H<sub>111</sub>N<sub>11</sub>O<sub>12</sub>); Sigma 30024, 25 mg, store commercial stock at 	2-8°C; M = 1202.61 g·mol<sup>-1</sup> (≥ 95%).-->
+:::: '''Preparation of 400 µM stock solution''' (dissolved in ethanol abs.)
-::: '''Preparation of 400 µM stock solution''' (dissolved in 99.9% ethanol)
+::::# Weigh 1 mg of CsA and dissolve in 2.11 ml of ethanol abs..
-::::# Weigh 1 mg of CsA and dissolve in 2.11 ml of ethanol absolute (99.9%).
 ::::# Divide in aliquots.
 ::::# Store frozen at -20 °C.
@@ Line 26: / Line 38: @@
-== Inhibition of PTP by CsA ==
+== Inhibition of mtPTP 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<sup>-</sup>/<sup>-</sup> mice increases stability of brain mitochondria against Ca<sup>2+</sup> 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.