title: Arginine deiminase modulates endothelial tip cells via excessive synthesis of reactive oxygen species.
abstract: ADI (arginine deiminase), an enzyme that hydrolyses arginine, has been reported as an anti-angiogenesis agent. However, its molecular mechanism is unclear. We have demonstrated for the first time that ADI modulates the angiogenic activity of endothelial tip cells. By arginine depletion, ADI disturbs actin filament in endothelial tip cells, causing disordered migratory direction and decreased migration ability. Furthermore, ADI induces excessive synthesis of ROS (reactive oxygen species), and activates caspase 8-, but not caspase 9-, dependent apoptosis in endothelial cells. These findings provide a novel mechanism by which ADI inhibits tumour angiogenesis through modulating endothelial tip cells.
authors.affiliation: Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuo
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Song
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Luo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D017209:Apoptosis; D001120:Arginine / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D017382:Reactive Oxygen Species; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D006867:Hydrolases; D053181:Caspase 8; C019723:arginine deiminase