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Mechanisms involved in the antiplatelet effect of C-phycocyanin

Published online by Cambridge University Press:  08 March 2007

Hui-Fen Chiu ,
Shih-Ping Yang ,
Yu-Ling Kuo ,
Yuan-Shu Lai  and
Tz-Chong Chou
Hui-Fen Chiu
Affiliation:
Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
Shih-Ping Yang
Affiliation:
Division of Cardiology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China
Yu-Ling Kuo
Affiliation:
Department of Physiology and Biophysics, National Defense Medical Center, No. 161, Min-Chuan E. Rd., Sec. 6, Taipei, Taiwan, Republic of China
Yuan-Shu Lai
Affiliation:
Intensive Care Unit, Chung-Hsiao Municipal Hospital Taipei-City, Taipei, Taiwan, Republic of China
Tz-Chong Chou*
Affiliation:
Department of Physiology and Biophysics, National Defense Medical Center, No. 161, Min-Chuan E. Rd., Sec. 6, Taipei, Taiwan, Republic of China
*
*corresponding author: Dr Tz-Chong Chou, fax +886 2 8792 7202, email [email protected]
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Abstract

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C-phycocyanin (cpc), a biliprotein isolated from Spirulina platensis, has been reported to exert many therapeutic and nutritional values. In the present study, we examined whether cpc has an antiplatelet activity in vitro and further investigated the possible anti-aggregatory mechanisms involved. Our results showed that preincubation of cpc (1–50μg/ml) with rabbit washed platelets dose-dependently inhibited the platelet aggregation induced by collagen (10μg/ml) or arachidonic acid (100μm), with an ic50 of about 10μg/ml. Furthermore, the thromboxane B2 formation caused by collagen or arachidonic acid was significantly inhibited by cpc due to suppression of cyclooxygenase and thromboxane synthase activity. Similarly, the rise of platelet intracellular calcium level stimulated by arachidonic acid and collagen-induced platelet membrane surface glycoprotein IIb/IIIa expression were also attenuated by cpc. In addition, cpc itself significantly increased the platelet membrane fluidity and the cyclic AMP level through inhibiting cyclic AMP phosphodiesterase activity. These findings strongly demonstrate that cpc is an inhibitor of platelet aggregation, which may be associated with mechanisms including inhibition of thromboxane A2 formation, intracellular calcium mobilization and platelet surface glycoprotein IIb/IIIa expression accompanied by increasing cyclic AMP formation and platelet membrane fluidity.

Keywords

C-phycocyaninPlatelet aggregationThromboxaneB2Cyclic AMP
Type
Research Article
Information
British Journal of Nutrition , Volume 95 , Issue 2 , February 2006 , pp. 435 - 440
Copyright
Copyright © The Nutrition Society 2006

References

Antiplatelet Trialists Collaborative overview of randomised trial of antiplatelet therapy. I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients Br Med J 308 81–106 1994CrossRefGoogle Scholar
Bell, RL, Kennerly, DA, Stanford, N & Majerus, PWDiglyceride lipase: a pathway for arachidonic acid release from human platelets Proc Natl Acad Sci USA 76 1790–1792 1979CrossRefGoogle ScholarPubMed
Berns, DSProtein aggregation in phycocyanin – osmotic pressure studies Biochem Biophys Res Commun 38 65–73 1970CrossRefGoogle ScholarPubMed
Billah, MM, Lapetina, EG & Cuatrecasas, PPhospholipase A 2 activity specific for phosphatidic acid: a possible mechanism for the production of arachidonic acid in platelets J Biol Chem 1981 256 5399–5403.CrossRefGoogle ScholarPubMed
Billah, MM, Lapetina, EG, Cuatrecasas, PPhospholipase A 2 activity specific for phosphatidic acid: a possible mechanism for the production of arachidonic acid in platelets J BiolChem 256 5399–5403 1981Google ScholarPubMed
Chang, Y, Chen, TL, Wu, GJ, Hsiao, G, Shen, MY, Lin, KH, Chou, DSLin, CHSheu, JRMechanisms involved in the antiplatelet activity of ketamine in human platelets. J Biomed Sci 2004 11 764–772CrossRefGoogle ScholarPubMed
Chou, TC, Fu, E, Wu, CJ & Yeh, JHChitosan enhances platelet adhesion and aggregation Biochem Biophy Res Comm 302 480–483 2003CrossRefGoogle ScholarPubMed
Chou, TC, sLi, CY, Lee, AR & Wu, TMMechanism of inhibition of platelet aggregation by HCL-31D Eur J Pharmacol 387 125–131 2000CrossRefGoogle ScholarPubMed
Demopoulos, CA, Karantonis, HC &Antonopoulou, SPlatelet activating factor – a molecular link between atherosclerosis theories Eur J Lipid Sci Technol 105 705–716 2003CrossRefGoogle Scholar
Enouf, J, Bredoux, R, Bourdeau, N, Giraud, F, Le Peuch, C, Lebret, M & Levy-Toledano, SRelationship between cAMP and Ca 2+ fluxes in human platelet membranes Biochimie 69 297–304 1987CrossRefGoogle Scholar
Feinstein, MB, Zavoico, GB & Halenda, SPCalcium and cyclic AMP: antagonistic modulators of platelet function. In The Platelets – Physiology and Pharmacology. [Longerecker, GL] Orlando, FL Academic Press 1985 237–269.Google Scholar
Herman, AGRationale for the combination of anti-aggregating drugs Thromb Res 92 S17–S21 1998CrossRefGoogle ScholarPubMed
Iuliano, L, Colavita, AR, Leo, R, Pratico, D & Violi, FOxygen free radicals and platelet activation Free Radic Biol Med 22 999–1006 1997CrossRefGoogle ScholarPubMed
Kay, RAMicroalgae as food and supplement Crit Rev Food Sci Nutr 30 555–573 1991CrossRefGoogle ScholarPubMed
roll, M & Schager, ABiochemical mechanisms of platelet activation Blood 74 1185–1195 1989Google Scholar
Le QuanSang, KH,Mazeaud, M, Astarie, C, Duranthon, VDriss, FDevynck, MAPlasma lipids and platelet membrane fluidity in essential hypertension Thromb Haemost 69 70–76 1993Google Scholar
Leo, R, Pratico, D, Iuliano, L, Pulcinelli, FM, Ghiselli, A, Pignatelli, P, Colavita, AR, FitzGerald, GA & Violi, FPlatelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and then reoxygenated Circulation 1997 95 885–891.CrossRefGoogle ScholarPubMed
Phillips, DR, Charo, IF & Scarborough, RMGPIIb-IIIa: the responsive integrin. Thromb Res 1991 65 359–362Google ScholarPubMed
Pignatelli, P, Pulcinelli, FM, Lenti, L, Gazzaniga, PP & Violi, FHydrogen peroxide is involved in collagen-induced platelet activation. Blood 1998 91 484–490CrossRefGoogle ScholarPubMed
Pribluda, V & Rotman, ADynamics of membrane–cytoskeleton interactions in activated blood platelets. Biochemistry 1982 21 2825–2832CrossRefGoogle ScholarPubMed
Reddy, CM, Bhat, VB, Kiranmai, G, Reddy, MN, Reddanna, P & Madyastha, KMSelective inhibition of cyclooxygenase-2 by C-Phycocyanin, a biliprotein from Spirulina platensis. Biochem Biophys Res Commun 2000 277 599–603CrossRefGoogle ScholarPubMed
Remirez, D, González, A, Merino, N, González, R, Ancheta, O, Romay, C & Rodríguez, SEffect of phycocyanin in zymosaninduced arthritis in mice. Drug Dev Res 1999 48 70–753.0.CO;2-N>CrossRefGoogle Scholar
Romay, C, Armesto, J, Remirez, D, Gonzalez, R, Ledon, N & Garcia, IAntioxidant and anti-inflammatory properties of C-Phycocyanin from blue green algae Inflamm Res 1998 47 36–41CrossRefGoogle ScholarPubMed
Romay, C, Delgado, R, Remirez, D, Gonzalez, R & Rojas, AEffects of phycocyanin extract on tumor necrosis factor-alpha and nitrite levels in serum of mice treated with endotoxin. Arzneimittel-Forschung 2001 51 733–736Google ScholarPubMed
Romay, C, Gonzalez, R, Ledon, N, Remirez, D & Rimbau, VCPhycocyanin:a biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr Protein Pept Sci 2003 4 207–216CrossRefGoogle ScholarPubMed
Romay, C, Ledon, N & Gonzalez, REffects of phycocyanin extract on prostaglandin E2 levels in mouse ear inflammation test. Arzneimittel-Forschung 2000 50 1106–1109Google ScholarPubMed
Ruggeri, ZMPlatelets in atherothrombosis. Nature Med 2002 8 1227–1234CrossRefGoogle ScholarPubMed
Shattil, SJ & Cooper, RAMembrane microviscosity and human platelet function. Biochemistry 1976 15 4832–4837CrossRefGoogle ScholarPubMed
Sheu, JR, Hsiao, G, Shen, MY, Fong, TH, Chen, YW, Lin, CH & Chou, DSMechanisms involved in the antiplatelet activity of magnesium in human platelets. Br J Haematol 2002 119 1033–1041CrossRefGoogle ScholarPubMed
Sheu, JR, Hung, WC, Lee, LW, Chang, PT, Kan, YC & Yen, MHMechanisms involved in the antiplatelet activity of naloxone in human platelets. Biochem Biophys Res Commun 1997 231 12–16CrossRefGoogle ScholarPubMed
Srivastava, K & Dash, DAltered membrane fluidity and signal transduction in the platelets from patients of thrombotic stroke. Mol Cell Biochem 2001 224 143–149CrossRefGoogle ScholarPubMed
Steiner, MVitamin E changes the membrane fluidity of human platelets. Biochim Biophys Acta 1981 640 100–105CrossRefGoogle ScholarPubMed
Tandon, NN, Harmon, JT, Jamieson, GAInfluence of membrane fluidity on platelet activation in cholesterol-modified and hypercholesterolemic platelets. In Lipid Domains and the Relationship to Membrane Function. (Aloia, RC, Curtain, CC and Gordon, LM) New York: Alan R. Liss Inc. 1988 83–99Google Scholar
Vadiraja, BB, Gaijwad, NW & Madyastha, KMHepatoprotective effect of C-Phycocyanin: protection for carbon tetrachloride and R(+)-pulegone mediated hepatotoxicity in rats. Biochem Biophys Res Commun 1998 249 428–431CrossRefGoogle Scholar
Winocour, PD, Bryszewska, M, Watala, C, Rand, ML, Epand, RM, Kinlough-Rathbone, RL, Packham, MA & Mustard, JFReduced membrane fluidity in platelets from diabetic patients. Diabete 1990 39 241–244CrossRefGoogle ScholarPubMed