SERCA2b activity is regulated by cyclophilins in human platelets.
OBJECTIVE
The role of cyclophilins (chaperones that are widely expressed in different cell types, including human platelets) was explored in sarcoendoplasmic calcium (Ca(2+)) adenosine triphosphatase (SERCA) activity.


RESULTS
Cyclophilin inhibition by cyclosporin A (CsA) evoked a time- and concentration-dependent reduction of Ca(2+) uptake by SERCA2b. However, other Ca(2+)-adenosine triphosphatases expressed in platelets, such as SERCA3 and plasma membrane Ca(2+) adenosine triphophatase, remained unaltered after CsA treatment. Cypermethrin, a non-CsA-related calcineurin inhibitor, did not alter SERCA2b activity. Furthermore, SERCA2b was affected by other CsA analogues, which do not interfere with calcineurin, such as PKF-211-811-NX5 (NIM811) and sanglifehrin A. Inhibition of the immunophilin family members using FK506 (tacrolimus) did not alter SERCA2b ability to sequester Ca(2+) into the dense tubular system. Coimmunoprecipitation experiments confirmed that cyclophilin A associates with SERCA2b and stromal interaction molecule-1 in resting platelets. This interaction is attenuated by the physiological agonist thrombin but enhanced by treatment with CsA or sanglifehrin A.


CONCLUSIONS
Cyclophilin A is a regulator of SERCA2b in human platelets.
Department of Physiology, University of Extremadura, Avd. Universidad s/n, Cáceres 10071, Spain.
Juan A
JA
Rosado
Jose A
JA
Pariente
Gines M
GM
Salido
Pedro C
PC
Redondo
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D021984:Cyclophilin A / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020104:Immunophilins / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016572:Cyclosporine; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D021984:Cyclophilin A; D020104:Immunophilins; C506946:ATP2A2 protein, human; C506949:ATP2A3 protein, human; D002118:Calcium