| First Author | Kim YM | Year | 2006 |
| Journal | Cancer Res | Volume | 66 |
| Issue | 12 | Pages | 6167-74 |
| PubMed ID | 16778190 | Mgi Jnum | J:110106 |
| Mgi Id | MGI:3639373 | Doi | 10.1158/0008-5472.CAN-05-3640 |
| Citation | Kim YM, et al. (2006) Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Cancer Res 66(12):6167-74 |
| abstractText | 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, diphenylene-iodonium 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. |
