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Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis
- Title
- Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis
- Authors
- Kim Y.M.; Kim K.E.; Koh G.Y.; Ho Y.-S.; Lee K.-J.
- Ewha Authors
- 이공주
- SCOPUS Author ID
- 이공주
- Issue Date
- 2006
- Journal Title
- Cancer Research
- ISSN
- 0008-5472
- Citation
- Cancer Research vol. 66, no. 12, pp. 6167 - 6174
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Angiopoietin-1 (Ang1) mediates angiogenesis by enhancing endothelial cell survival and migration. It is also known that Ang1 activates Tie2, an endothelial-specific tyrosine kinase receptor, but the molecular mechanism of this process is not clear. In this study, we investigated whether reactive oxygen species (ROS) production plays a role in Ang1-mediated angiogenesis. We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenyleneiodonium chloride, and rotenone. The Ang1-induced ROS was identified as hydrogen peroxide (H2O2) using adenovirus-catalase infection. Removal of H2O2 by adenovirus-catalase significantly suppressed Ang1-induced in vitro endothelial cell migration, in vivo tubule formation and angiogenesis, and activation of p44/42 mitogen-activated protein kinase (MAPK), involved in cell migration, and delayed the deactivation of Akt phosphorylation involved in cell survival. Supporting to in vitro data, Ang1-induced vascular remodeling in catalase (-/-) mice was more prominent than in catalase (+/+) mice: Ang1-induced increases of the diameter of terminal arterioles and the postcapillary venules in catalase (-/-) mice were significant compared with catalase (+/+) mice. These results show that Ang1-induced H2O2 plays an important role in Ang1-mediated angiogenesis by modulating p44/42 MAPK activity. ©2006 American Association for Cancer Research.
- DOI
- 10.1158/0008-5472.CAN-05-3640
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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