Document Detail


Inhibitory effect of ginkgolide B on platelet aggregation in a cAMP- and cGMP-dependent manner by activated MMP-9.
MedLine Citation:
PMID:  17927900     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 microg/ml)- stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metalloproteinase- 9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular Ca2+ mobilization, and thromboxane A2 (TXA2) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or TXA2 synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular Ca2+ mobilization and TXA2 production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.
Authors:
Hyun-Jeong Cho; Kyung-Soo Nam
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biochemistry and molecular biology     Volume:  40     ISSN:  1225-8687     ISO Abbreviation:  J. Biochem. Mol. Biol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-10-11     Completed Date:  2008-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9702084     Medline TA:  J Biochem Mol Biol     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  678-83     Citation Subset:  IM    
Affiliation:
College of Medicine and Cardiovascular Medical Research Center, Dongguk University, Gyeongju 780-714, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Platelets / drug effects,  metabolism
Calcium / metabolism
Collagen / pharmacology
Cyclic AMP / metabolism*
Cyclic GMP / metabolism*
Enzyme Activation / drug effects
Ginkgolides / chemistry,  pharmacology*
Lactones / chemistry,  pharmacology*
Matrix Metalloproteinase 9 / metabolism*
Molecular Structure
Platelet Aggregation / drug effects*
Rats
Rats, Sprague-Dawley
Thromboxane A2 / metabolism
Chemical
Reg. No./Substance:
0/Ginkgolides; 0/Lactones; 57576-52-0/Thromboxane A2; 60-92-4/Cyclic AMP; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP; 9007-34-5/Collagen; 99796-69-7/ginkgolide B; EC 3.4.24.35/Matrix Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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