Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates collagen-mediated platelet activation through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). However, the function of CEACAM1's extracellular cleavage fragments is currently unknown. In the present study, we used mass spectrometry (MS) to identify 9 cleavage fragments shed by matrix metallopeptidase 12 (MMP-12), and then we synthesized peptides with sequences corresponding to the fragments. QLSNGNRTLT (QLSN), a peptide from the A1-domain of CEACAM1, significantly attenuated collagen-induced platelet aggregation. QLSN also attenuated platelet static adhesion to collagen. Additionally, QLSN reduced human platelet secretion and integrin alpha(IIb)beta(3) activation in response to glycoprotein VI (GPVI)-selective agonist, convulxin. Correspondingly, QLSN treatment significantly decreased convulxin-mediated phosphorylation of Src, protein kinase B (Akt), spleen tyrosine kinase (Syk) and phospholipase C gamma 2 (PLC gamma 2) in human platelets. These data indicate that the CEACAM1-derived peptide QLSN inhibits GPVI-mediated human platelet activation. QLSN could potentially be developed as a novel antiplatelet agent.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81160025, 81560075, 81860074]; Applied Basic Research Foundation of Yunnan Province [2018FE001 (-005)]
第一作者机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Cardiol, Lab Mol Cardiol, Kunming, Yunnan, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Cardiol, Lab Mol Cardiol, Kunming, Yunnan, Peoples R China
推荐引用方式(GB/T 7714):
Ye Yujia,Wan Wen,Wang Jing,et al.The CEACAM1-derived peptide QLSN impairs collagen-induced human platelet activation through glycoprotein VI[J].BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY.2020,84(1):85-94.doi:10.1080/09168451.2019.1662277.
APA:
Ye, Yujia,Wan, Wen,Wang, Jing,Hu, Wei,Wang, Huawei...&Meng, Zhaohui.(2020).The CEACAM1-derived peptide QLSN impairs collagen-induced human platelet activation through glycoprotein VI.BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY,84,(1)
MLA:
Ye, Yujia,et al."The CEACAM1-derived peptide QLSN impairs collagen-induced human platelet activation through glycoprotein VI".BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 84..1(2020):85-94