Inhibitory mechanisms of activated matrix metalloproteinase-9 on platelet activation.

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Taipei Medical University Institutional Repository > 醫學院 > 醫學科學研究所 > 期刊論文 > Item 987654321/10279

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题名:	Inhibitory mechanisms of activated matrix metalloproteinase-9 on platelet activation.
作者:	許準榕 Lee;Y.M.;Lee;J.J.;Shen;M.Y.;Hsiao;G.;Sheu;J.R.
贡献者:	醫學科學研究所
日期:	2006
上传时间:	2009-10-12 15:31:34 (UTC+8)
摘要:	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 diphenylhexatriene. 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 μg/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.
關聯:	Eur. J. Pharmacol.(537):52-58.
数据类型:	article
显示于类别:	[醫學科學研究所] 期刊論文

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