Source:http://linkedlifedata.com/resource/pubmed/id/20050964
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2010-10-27
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| pubmed:abstractText |
Kringle 5(K5) is the fifth kringle domain of human plasminogen and its anti-angiogenic activity is more potent than angiostatin that includes the first four kringle fragment of plasminogen. Our recent study demonstrated that K5 suppressed hepatocarcinoma growth by anti-angiogenesis. To find high efficacy and minimal peptide sequence required for the anti-angiogenic and anti-tumour activities of K5, two deletion mutants of K5 were generated. The amino acid residues outside kringle domain of intact K5 (Pro452-Ala542) were deleted to form K5mut1(Cys462-Cys541). The residue Cys462 was deleted again to form K5mut2(Met463-Cys541). K5mut1 specifically inhibited proliferation, migration and induced apoptosis of endothelial cells, with an apparent two-fold enhanced activity than K5. Intraperitoneal injection of K5mut1 resulted in more potent tumour growth inhibition and microvessel density reduction than K5 both in HepA-grafted and Bel7402-xenografted hepatocarcinoma mouse models. These results suggested that K5mut1 has more potent anti-angiogenic activity than intact K5. K5mut2, which lacks only the amino terminal cysteine of K5mut1, completely lost the activity, suggesting that the kringle domain is essential for the activity of K5. The activity was enhanced to K5mut1 level when five acidic amino acids of K5 in NH(2) terminal outside kringle domain were replaced by five serine residues (K5mut3). The shielding effect of acidic amino acids may explain why K5mut1 has higher activity. K5, K5mut1 and K5mut3 held characteristic ?-sheet spectrum while K5mut2 adopted random coil structure. These results suggest that K5mut1 with high efficacy is the minimal active peptide sequence of K5 and may have therapeutic potential in liver cancer.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1582-4934
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| pubmed:author | |
| pubmed:copyrightInfo |
© 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
14
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2519-30
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| pubmed:meshHeading |
pubmed-meshheading:20050964-Amino Acid Sequence,
pubmed-meshheading:20050964-Angiogenesis Inhibitors,
pubmed-meshheading:20050964-Angiostatins,
pubmed-meshheading:20050964-Animals,
pubmed-meshheading:20050964-Antineoplastic Agents,
pubmed-meshheading:20050964-Carcinoma, Hepatocellular,
pubmed-meshheading:20050964-Cell Line, Tumor,
pubmed-meshheading:20050964-Cells, Cultured,
pubmed-meshheading:20050964-Endothelial Cells,
pubmed-meshheading:20050964-Humans,
pubmed-meshheading:20050964-Kringles,
pubmed-meshheading:20050964-Liver Neoplasms,
pubmed-meshheading:20050964-Male,
pubmed-meshheading:20050964-Mice,
pubmed-meshheading:20050964-Mice, Nude,
pubmed-meshheading:20050964-Molecular Sequence Data,
pubmed-meshheading:20050964-Neovascularization, Pathologic,
pubmed-meshheading:20050964-Plasminogen,
pubmed-meshheading:20050964-Random Allocation,
pubmed-meshheading:20050964-Sequence Deletion
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| pubmed:year |
2010
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| pubmed:articleTitle |
High efficacy and minimal peptide required for the anti-angiogenic and anti-hepatocarcinoma activities of plasminogen K5.
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| pubmed:affiliation |
Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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