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Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation
Zhu, Zhixiang; Zhang, Quanbin2; Chen, Lihong; Ren, Shuang; Xu, Pingxing; Tang, Yu; Luo, Dali1
2010-05-01
Source PublicationTHROMBOSIS RESEARCH
Volume125Issue:5Pages:419-426
SubtypeArticle
AbstractAlgal fucoidans possess a wide variety of biological activities, including anticoagulation and antithrombosis, making them potential candidates for clinical use. We assessed the antiaggregant, anticoagulant and antithrombotic activities and the underlying mechanism of the low-and high-molecular weight fucoidans from the seaweed Laminaria japonica of Qingdao, China (F-Q and HMWF-Q). In the platelets of rats and humans, HMWF-Q demonstrated a pro-aggregation response, whereas F-Q (like the commercially purchased fucoidan (F-S) and heparin), showed an inhibitory effect on thrombin-induced aggregation with an IC(50) of 8 mu g/mL, approximately five times lower than those of F-S and heparin. In the activated partial thromboplastin time test, F-Q (40 mu g/mL) demonstrated less potent effect than F-S (40 mu g/mL) and heparin (7 mu g/mL); 162 +/- 2.4 s vs. 250 +/- 13.2 s and > 300 s, p < 0.01, respectively. It was also less effective than F-S on inhibiting thrombin catalyzed fibrinogen cleavage (IC(50) 10 mu g/mL vs. 2.8 mu g/mL) in vitro and rat thrombosis in vivo at 3 mg/kg (i.v.). The inhibitory effects of F-Q and heparin on thrombin activity were strikingly enhanced by either antithrombin (AT) or heparin cofactor II (HCII). A direct interaction of F-S with thrombin, and F-Q or heparin with AT was demonstrated in both fluorescence quenching and PAGE analysis. Additionally, a pro-aggregation effect and an enhancement of thrombin activity were also observed with F-S, but not with F-Q or heparin, treatment. These results indicate that F-Q inhibits thrombin via activation of AT and HCII, whereas F-S mainly interacts directly with thrombin. Importantly, F-Q shows a higher specificity for hypoaggregation and a weaker effect for anticoagulant profiles than heparin and F-S. Therefore, F-Q could be a promising candidate for the treatment of thrombosis-related cardiovascular diseases. (C) 2010 Elsevier Ltd. All rights reserved.
KeywordFucoidan Heparin Aggregation Coagulation Thrombin Thrombosis
DOI10.1016/j.thromres.2010.02.011
Indexed BySCI
Language英语
WOS IDWOS:000277209200010
Citation statistics
Cited Times:84[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/32735
Collection海洋生物技术研发中心
Affiliation1.Capital Med Univ, Sch Chem Biol & Pharmaceut Sci, Dept Pharmacol, Beijing 100069, Peoples R China
2.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China
Recommended Citation
GB/T 7714
Zhu, Zhixiang,Zhang, Quanbin,Chen, Lihong,et al. Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation[J]. THROMBOSIS RESEARCH,2010,125(5):419-426.
APA Zhu, Zhixiang.,Zhang, Quanbin.,Chen, Lihong.,Ren, Shuang.,Xu, Pingxing.,...&Luo, Dali.(2010).Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation.THROMBOSIS RESEARCH,125(5),419-426.
MLA Zhu, Zhixiang,et al."Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation".THROMBOSIS RESEARCH 125.5(2010):419-426.
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