| Metabolism of rabbit angiostatin glycoforms I and II in rabbits: angiostatin-I leaves the intravascular space faster and appears to have greater anti-angiogenic activity than angiostatin-II. | |
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MedLine Citation:
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PMID: 11477374 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Plasminogen (PLG) exists in the circulation as two glycoforms, I and II. Angiostatin (AST) is a polypeptide that has been cleaved from the kringle region of PLG and has strong anti-angiogenic properties. AST-I and AST-II, which consisted only of kringles 1 through 3, were prepared by the action of urokinase on purified rabbit PLG-I and PLG-II, respectively, in the presence of N-acetyl cysteine, followed by affinity chromatography on lysine-Sepharose. Purified AST-I and AST-II were tested for functional activity with a chick chorioallantoic membrane (CAM) model; when similar amounts were applied to a 6-day CAM, AST-I was substantially more effective than AST-II in decreasing vascular supply to the CAM over a 72-hour period; this activity correlated with a loss of capillaries, probably through apoptosis of endothelial cells. Radiolabeled AST-I and AST-II (iodine 125 and iodine 131) were co-injected intravenously into healthy rabbits to determine their clearances from plasma measured over 3 days. Over a dose range of 0.08 to 2.7 microg/kg, the fractional catabolic rate within the intravascular space (j(3)) indicated that AST-I was cleared 3-fold to 4-fold more rapidly than AST-II (P < .001). The catabolic half-life of AST-I (2.01 +/- 0.19 days) was significantly less than that of AST-II (2.62 +/- 0.20 days). The faster clearance of AST-I from the intravascular space was matched by its more rapid passage than AST-II to the extravascular space of various organs over 60 minutes in vivo. This property of AST-I as compared with AST-II may partially explain its greater anti-angiogenic potential. From the plasma concentrations of PLG-I and PLG-II and their relative behaviors toward rabbit VX-2 lung tumors in vivo, we predict that substantially greater quantities of AST-II than AST-I may be released into the extravascular space of tumors. |
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Authors:
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M W Hatton; S Day; S M Southward; M Dereske; B Ross; E Seidlitz; G Singh; M Richardson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of laboratory and clinical medicine Volume: 138 ISSN: 0022-2143 ISO Abbreviation: J. Lab. Clin. Med. Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-07-30 Completed Date: 2001-08-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375375 Medline TA: J Lab Clin Med Country: United States |
Other Details:
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Languages: eng Pagination: 83-93 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, and the Hamilton Regional Cancer Centre, Ontario, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiostatins Animals Capillaries / metabolism Chick Embryo Endothelium, Vascular / metabolism Iodine Radioisotopes / diagnostic use Isomerism Neovascularization, Physiologic / drug effects* Peptide Fragments / chemistry, isolation & purification, pharmacokinetics* Plasminogen / chemistry, isolation & purification, pharmacokinetics* Rabbits Species Specificity Tarsal Joints / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Iodine Radioisotopes; 0/Peptide Fragments; 86090-08-6/Angiostatins; 9001-91-6/Plasminogen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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