C-phycocyanin, a very potent and novel platelet aggregation inhibitor from Spirulina platensis.
The aim of this study was to systematically examine the inhibitory mechanisms of C-phycocyanin (C-PC), one of the major phycobiliproteins of Spirulina platensis (a blue-green alga), in platelet activation. In this study, C-PC concentration-dependently (0.5-10 nM) inhibited platelet aggregation stimulated by agonists. C-PC (4 and 8 nM) inhibited intracellular Ca2+ mobilization and thromboxane A2 formation but not phosphoinositide breakdown stimulated by collagen (1 microg/mL) in human platelets. In addition, C-PC (4 and 8 nM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation. Rapid phosphorylation of a platelet protein of Mw 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (150 nM). This phosphorylation was markedly inhibited by C-PC (4 and 8 nM). In addition, C-PC (4 and 8 nM) markedly reduced the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 microg/mL)-activated platelets. The present study reports on a novel and very potent (in nanomolar concentrations) antiplatelet agent, C-PC, which is involved in the following inhibitory pathways: (1) C-phycocyanin increases cyclic GMP/VASP Ser157 phosphorylation and subsequently inhibits protein kinase C activity, resulting in inhibition of both P47 phosphorylation and intracellular Ca2+ mobilization, and (2) C-PC may inhibit free radicals (such as hydroxyl radicals) released from activated platelets, which ultimately inhibits platelet aggregation. These results strongly indicate that C-PC appears to represent a novel and potential antiplatelet agent for treatment of arterial thromboembolism.
Hsiao
George
G
Graduate Institute of Pharmacology, and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 110, Taiwan.
Chou
Po-Hsiu
PH
Shen
Ming-Yi
MY
Chou
Duen-Suey
DS
Lin
Chien-Huang
CH
Sheu
Joen-Rong
JR
D001426:Bacterial Proteins / Q000737:chemistry*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D010716:Phosphatidylinositols / Q000097:blood; D010766:Phosphorylation; D010798:Phycocyanin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry; D011487:Protein Conformation / Q000187:drug effects; D053545:Spirulina
D001426:Bacterial Proteins; D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010798:Phycocyanin; D003094:Collagen; D002118:Calcium