Sulforaphane attenuates platelet granule secretion through down-regulating glycoprotein VI-mediated p38 MAPK/cPLA2 signaling pathway
Sulforaphane attenuates platelet granule secretion through down-regulating glycoprotein VI-mediated p38 MAPK/cPLA2 signaling pathway
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DOI：
10.1080/19476337.2023.2173307
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发表时间：
2023-02
期刊：
影响因子：
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通讯作者：
Xinhui Huang;Xinyu Zhou;Chunting Wu;Weiqi Li;Yongjie Ma;Qilian He;Fuli Ya
中科院分区：
文献类型：
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作者：
Xinhui Huang;Xinyu Zhou;Chunting Wu;Weiqi Li;Yongjie Ma;Qilian He;Fuli Ya
糖蛋白VI （GPVI）是血小板表面的主要胶原受体，在介导颗粒分泌和动脉粥样硬化血栓形成中起重要作用。萝卜硫素（sulforaphan， SFN）是十字花科蔬菜中富含的一种膳食异硫氰酸盐，具有多种生物活性。本研究旨在探讨SFN在体外对gpvi介导的信号通路和血小板颗粒分泌的影响。我们在此证明了SFN大大降低了人凝胶过滤血小板对胶原蛋白的颗粒分泌，包括抑制CD62P和CD63的表达以及PF4、CCL5和ATP的释放。在机制上，SFN的这些抑制作用主要是通过其抑制胞质磷脂酶A2 （cPLA2）磷酸化和血栓素A2 （TxA2）的生成来介导的。此外，SFN并未进一步降低p38 MAPK抑制剂SB203580对cPLA2磷酸化、TxA2生成和颗粒分泌的抑制作用。因此，SFN通过下调gpvi介导的p38 MAPK/cPLA2/TxA2信号通路来减弱血小板颗粒分泌，可能在心血管疾病中发挥重要的预防作用。
ABSTRACT Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and is important in mediating granule secretion and atherothrombosis. Sulforaphane (SFN), a dietary isothiocyanate enriched in cruciferous vegetables, exerts multiple biological activities. This study aimed to investigate the efficacy of SFN on GPVI-mediated signaling and platelet granule secretion in vitro. We herein demonstrated that SFN greatly attenuated granule secretion in human gel-filtered platelets in response to collagen, including inhibiting CD62P and CD63 expression and PF4, CCL5, and ATP release. Mechanistically, these inhibitory effects of SFN were mainly mediated by its attenuation of cytosolic phospholipase A2 (cPLA2) phosphorylation and thromboxane A2 (TxA2) generation. Moreover, SFN did not further decrease the inhibitory effects of p38 MAPK inhibitor SB203580 on cPLA2 phosphorylation, TxA2 generation and granule secretion. Thus, SFN attenuates platelet granule secretion via down-regulating GPVI-mediated p38 MAPK/cPLA2/TxA2 signaling, which may play important preventive roles in cardiovascular diseases.