Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation

	Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation
	Zhu, Zhixiang ; Zhang, Quanbin 2; Chen, Lihong ; Ren, Shuang ; Xu, Pingxing ; Tang, Yu ; Luo, Dali 1
刊名	THROMBOSIS RESEARCH
	2010-05-01
卷号	125 期号:5 页码:419-426
关键词	Fucoidan Heparin Aggregation Coagulation Thrombin Thrombosis
英文摘要	Algal 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.
收录类别	SCI
语种	英语
WOS记录号	WOS:000277209200010
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/32735]
专题	海洋研究所_海洋生物技术研发中心
作者单位	1.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
推荐引用方式 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.