Inhibitory mechanisms of activated matrix metalloproteinase-9 on platelet activation
Inhibitory mechanisms of activated matrix metalloproteinase-9 on platelet activation
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DOI：
10.1016/j.ejphar.2006.03.031
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发表时间：
2006-05-10
影响因子：
5
通讯作者：
Sheu, Joen-Rong
中科院分区：
文献类型：
--
作者：
Lee, Ye-Ming;Lee, Jie-Jen;Sheu, Joen-Rong
活化的基质金属蛋白酶-9（MMP-9）在血小板中的信号通路的细胞内机制尚未完全了解。因此，本研究的目的是进一步检查活化的MMP-9在防止血小板聚集中的作用。在这项研究中，激活的MMP-9时间依赖性（3-60分钟）抑制血小板聚集在洗涤的人血小板悬液激动剂刺激。然而，活化的MMP-9对FITC-triflavin与血小板糖蛋白IIb/IIIa复合物的结合没有显著影响。Triflavin是从蛇毒中纯化的糖蛋白IIb/IIIa复合物的特异性拮抗剂。此外，激活的MMP-9（21和90 ng/ml）显着降低标记的血小板膜的荧光强度与二苯基己烯。在存在活化的MMP-9（21和90 ng/ml）的情况下，凝血酶诱发的pHi升高被抑制。此外，激活的MMP-9（21和90 ng/ml）显着降低胶原（1 μ g/ml）激活的血小板中的羟基自由基的电子自旋共振（ESR）信号强度。这些结果提示活化MMP-9的抗血小板作用可能涉及以下途径：（1）活化MMP-9可诱导血小板膜构象改变和羟自由基形成，从而抑制血小板聚集;（2）激活的MMP-9也抑制Na+/H+交换，导致细胞内Ca 2+动员减少，并最终抑制血小板聚集。这项研究进一步提供了新的见解有关活化的MMP-9对血小板聚集的影响。(c)2006 Elsevier B. V.保留所有权利。
The intracellular mechanisms underlying the signaling pathways of activated matrix metalloproteinase-9 (MMP-9) in platelets are not yet completely understood. Therefore, the aim of this study was to further examine the effects of activated MMP-9 in preventing platelet aggregation. In this study, activated MMP-9 time-dependently (3-60 min) inhibited platelet aggregation in washed human platelet suspensions stimulated by agonists. However, activated MMP-9 had no significant effect on the binding of FITC-triflavin to the platelet glycoprotein IIb/IIIa complex. Triflavin is a specific antagonist of the glycoprotein IIb/IIIa complex purified from snake venom. Moreover, activated MMP-9 (21 and 90 ng/ml) markedly decreased the fluorescence intensity of platelet membranes tagged with diphenylhexattiene. The thrombin-evoked increase in pHi was inhibited in the presence of activated MMP-9 (21 and 90 ng/ml). In addition, activated MMP-9 (21 and 90 ng/ml) markedly reduced the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 mu g/ml)-activated platelets. These results indicate that the antiplatelet activity of activated MMP-9 may involve the following pathways: (1) activated MMP-9 may initially induce conformational changes in platelet membranes and hydroxyl radical formation, leading to inhibition of platelet aggregation; and (2) activated MMP-9 also inhibits the Na+/H+ exchanger, leading to reduced intracellular Ca2+ mobilization, and ultimately to inhibition of platelet aggregation. This study further provides new insights concerning the effects of activated MMP-9 on platelet aggregation. (c) 2006 Elsevier B.V. All rights reserved.