Ubiquitin C-terminal hydrolase-L1 plays a key role in angiogenesis by regulating hydrogen peroxide generated by NADPH oxidase 4

• Published in: Biochemical and biophysical research communications Vol. 495; no. 1; pp. 1567 - 1572
• Main Authors: Song, In-Kang, Kim, Hyun Jung, Magesh, Venkataraman, Lee, Kong-Joo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018
• Subjects: 60 APPLIED LIFE SCIENCES; ANGIOGENESIS; BRAIN; Cells, Cultured; Deubiquitination; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - physiology; Gene Expression Regulation, Enzymologic - physiology; HUMAN POPULATIONS; Humans; HYDROGEN PEROXIDE; Hydrogen Peroxide - metabolism; HYDROLASES; HYDROLYSIS; NADPH oxidase 4; NADPH Oxidase 4 - metabolism; Neovascularization, Physiologic - physiology; OXIDASES; Reactive Oxygen Species - metabolism; Receptors, Vascular Endothelial Growth Factor - metabolism; TUBULES; Ubiquitin Thiolesterase - metabolism; Ubiquitination - physiology; UCH-L1; Vascular Endothelial Growth Factor A - metabolism; VEINS; Angiogenesis; NADPH oxidase 4; Hydrogen peroxide; UCH-L1; Deubiquitination; Endothelial cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.11.051

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), which catalyzes the hydrolysis of ubiquitin esters and amides, is highly expressed in brain. Recently, UCH-L1 has been found to increase cancer cell migration and invasion by modulating hydrogen peroxide generated by NADPH oxidase 4 (NOX4). Because angiogenesis is also mediated by hydrogen peroxide, we explored the role of UCH-L1 in angiogenesis in human umbilical vein endothelial cells (HUVECs). Silencing UCH-L1 suppressed tubule formation in HUVECs, indicating that UCH-L1 promotes angiogenesis in vitro. This was confirmed using in vivo Matrigel plug studies of HUVECs, after overexpressing or silencing UCH-L1. Silencing UCH-L1 significantly suppressed VEGF-induced ROS levels as well as activation of VEGFR, both of which are required for angiogenesis. This study also showed that UCH-L1 promotes angiogenesis of HUVECs, as well as invasion in cancer cells, by up-regulating ROS by deubiquitination of NOX4, suggesting that UCH-L1 plays a key role in angiogenesis of HUVECS by regulating ROS levels by deubiquitination of NOX4.