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High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on alpha(IIb)beta(3) and platelet secretion
Lin,Lisha; Yang,Lian; Chen,Jun; Zhou,Lutan; Li,Sujuan; Gao,Na; Zhao,Jinhua
2021
发表期刊PLATELETS
ISSN0953-7104
卷号32期号:7页码:975-983
摘要Fucosylated glycosaminoglycan (FG) from sea cucumbers has been reported to have anticoagulant effects via targeting intrinsic tenase. However, FG from natural source also potentially poses risks due to its FXIIa activation and platelet aggregating effects. Here, we found that the effect of FG on human platelet aggregation depended on both the sulfation pattern and chain length. FGs with higher content of Fuc(2S4S) and larger molecular weight (>= 14 kD) had stronger activity. Both platelet aggregation and P-selectin expression induced by TaFG (an FG fromThelenota ananas) were decreased as the molecular weight reduced. Ticagrelor, aspirin and wortmannin completely blocked the secretion (ADP) but only partially blocked the aggregation induced by TaFG. Tirofiban an alpha(IIb)beta(3) antagonist however potently inhibited both the secretion and aggregation, with IC50 of 6.01 +/- 1.1.97 nM. Furthermore, TaFG could bind to human alpha(IIb)beta(3) with high affinity, and the affinities of two FGs were paralleled with their activity in platelet aggregation or activation. These results indicated that alpha(IIb)beta(3) played an important role in TaFG-induced platelet aggregation which was mediated by PI3K, and that platelet secretion was required for the amplification of aggregation.
关键词Aggregation fucosylated glycosaminoglycan human platelets secretion alpha(IIb beta 3) DEPOLYMERIZED HOLOTHURIAN GLYCOSAMINOGLYCAN INTRINSIC TENASE COMPLEX INTEGRIN ALPHA(IIB)BETA(3) ACTIVATION AGGLUTINATION RECEPTOR ADP INHIBITION GENERATION MECHANISM
DOI10.1080/09537104.2020.1820976
WOS记录号WOS:000572529300001
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/73028
专题中国科学院昆明植物研究所
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Yunnan Univ, Sch Chem Sci & Technol, Kunming 650091, Yunnan, Peoples R China
4.South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430074, Peoples R China
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GB/T 7714
Lin,Lisha,Yang,Lian,Chen,Jun,et al. High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on alpha(IIb)beta(3) and platelet secretion[J]. PLATELETS,2021,32(7):975-983.
APA Lin,Lisha.,Yang,Lian.,Chen,Jun.,Zhou,Lutan.,Li,Sujuan.,...&Zhao,Jinhua.(2021).High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on alpha(IIb)beta(3) and platelet secretion.PLATELETS,32(7),975-983.
MLA Lin,Lisha,et al."High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on alpha(IIb)beta(3) and platelet secretion".PLATELETS 32.7(2021):975-983.
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