World Library  
Flag as Inappropriate
Email this Article

Angiostatin

Article Id: WHEBN0000510485
Reproduction Date:

Title: Angiostatin  
Author: World Heritage Encyclopedia
Language: English
Subject: Angiogenesis inhibitor, Calreticulin, Angiogenesis inhibitors, Angiogenic proteins, Beta-lactoglobulin
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Angiostatin

Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor (i.e., it blocks the growth of new blood vessels), and it is currently undergoing clinical trials for its use in anticancer therapy.[1]

Contents

  • Structure 1
  • Generation 2
  • Biological activity 3
  • References 4
  • External links 5

Structure

Angiostatin is a 38 kDa fragment of a larger protein, plasmin (itself a fragment of plasminogen) enclosing three to five contiguous kringle modules. Each module contains two small beta sheets and three disulfide bonds.[2][3]

Generation

Angiostatin is produced, for example, by autoproteolytic cleavage of plasminogen, involving extracellular disulfide bond reduction by phosphoglycerate kinase. Furthermore, angiostatin can be cleaved from plasminogen by different metalloproteinases (MMPs), elastase, prostate-specific antigen (PSA), 13 KD serine protease, or 24KD endopeptidase.

Biological activity

Angiostatin is known to bind many proteins, especially to angiomotin and endothelial cell surface ATP synthase but also integrins, annexin II, C-met receptor, NG2 proteoglycan, tissue-type plasminogen activator, chondroitin sulfate proteoglycans, and CD26. Additionally, smaller fragments of angiostatin may bind several other proteins. There is still considerable uncertainty on its mechanism of action, but it seems to involve inhibition of endothelial cell migration,[4] proliferation and induction of apoptosis. It has been proposed that angiostatin activity is related, among other things, to the coupling of its mechanical and redox properties.[5]

References

  1. ^ Safety and Efficacy Study of rhAngiostatin Administered in Combination With Paclitaxel and Carboplatin to Patients With Non-Small-Cell Lung Cancer - Full Text View - ClinicalTrials.gov
  2. ^ Cao Y, Ji RW, Davidson D; et al. (November 1996). "Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells". The Journal of Biological Chemistry 271 (46): 29461–7.  
  3. ^ O'Reilly MS, Holmgren L, Shing Y; et al. (October 1994). "Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma". Cell 79 (2): 315–28.  
  4. ^ Redlitz A, Daum G, Sage EH (1999). "Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells". Journal of Vascular Research 36 (1): 28–34.  
  5. ^ Grandi F, Sandal M, Guarguaglini G, Capriotti E, Casadio R, Samorì B (November 2006). "Hierarchical mechanochemical switches in angiostatin". Chembiochem : a European Journal of Chemical Biology 7 (11): 1774–82.  

External links

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.