A new function for the calcineurin b subunit: antiplatelet aggregation and anticoagulation.
Calcineurin is the only Ca(2+) /calmodulin-dependent serine/threonine protein phosphatase. The roles of the cytosolic calcineurin have been well researched; however, the roles of the serum calcineurin remain unknown. Here, we report that the recombinant human calcineurin B subunit (CnB) can bind to rabbit platelets and show an antiplatelet aggregation activity. Furthermore, CnB exerts an anticoagulant effect by prolonging the activated partial thromboplastin time and thrombin time and reducing the plasma fibrinogen concentration in a dose-dependent manner. We further reveal that the functional domain associated with the anticoagulant activity of CnB is located in the C-terminus. Hemolysis test and intravenous stimulation study show that the recombinant CnB does not cause obvious hemolysis and is safe for intravenous injection. These results reveal a new function of calcineurin B subunit. They also give an explanation for the roles of calcineurin B subunit in serum and point to a possible implication in antithrombotic therapy.
Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, People's Republic of China.
Zhenyi
Z
Su
Shuai
S
Xin
Jing
J
Li
Junxia
J
Guo
Xianlian
X
Long
Jinbo
J
Cheng
Qun
Q
Wei
D000818:Animals; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism / Q000494:pharmacology*; D004431:Ear, External / Q000033:anatomy & histology / Q000098:blood supply / Q000187:drug effects; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000378:metabolism / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012756:Sheep
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D005340:Fibrinogen; D019703:Calcineurin