caa a22 4500 445326565 CHVBK 20180317142722.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10989-011-9269-5 doi (NATIONALLICENCE)springer-10.1007/s10989-011-9269-5 NOX4-Derived Reactive Oxygen Species Drive Apelin-13-Induced Vascular Smooth Muscle Cell Proliferation via the ERK Pathway [Elektronische Daten] [Lanfang Li, Fang Li, Feng Li, Xiaohuan Mao, Li Yang, Hao Huang, Yu Guo, Linxi Chen, Jian Li] Apelin is the endogenous ligand of the G-protein-coupled receptor, apelin-angiotensin receptor-like 1 (APJ). Vascular smooth muscle cells express both apelin and APJ, which are important regulatory factors in the cardiovascular system. Apelin-13 significantly stimulated vascular smooth muscle cell proliferation. However, little is known about the precise cellular mechanisms responsible for vascular smooth muscle cell proliferation induced by apelin-13. Here, we present novel data that indicate the key role of NADPH oxidase 4-derived reactive oxygen species in proliferation of vascular smooth muscle cells treated with apelin-13. Apelin-13 stimulated reactive oxygen species production in a concentration- and time-dependent manner. Furthermore, DPI impaired apelin-13-induced reactive oxygen species generation and vascular smooth muscle cell proliferation. Apelin-13-treatment increased the expression of NADPH oxidase 4 in a dose-dependent manner. Down-regulation of NADPH oxidase 4 using siRNA prevented apelin-13-induced reactive oxygen species generation and vascular smooth muscle cell proliferation. An increase in reactive molecules can trigger the activation of ERK stress-sensitive signaling pathways. Additionally, siRNA-NOX4 and DPI reversed the phosphorylation of ERK induced by apelin-13. Apelin-13 induced vascular smooth muscle cell proliferation by NOX4-derived ROS via the ERK signaling pathway. Springer Science+Business Media, LLC, 2011 G protein coupled receptor nationallicence Reactive oxygen species nationallicence NADPH oxidase nationallicence Vascular smooth muscle cell nationallicence Proliferation nationallicence DPI : Diphenyliodinium nationallicence JNK : Jun N-terminal kinase nationallicence L-NAME : NG-Nitro-l-arginine methyl ester nationallicence NOX : NADPH oxidase nationallicence RNAi : RNA interference nationallicence siRNA : Small interfering RNA nationallicence ROS : Reactive oxygen species nationallicence Li Lanfang Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Li Fang Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Li Feng Department of Physiology, Hunan College of Traditional Chinese Medicine, 410007, Changsha, People's Republic of China aut Mao Xiaohuan Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Yang Li Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Huang Hao Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Guo Yu Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Chen Linxi Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut Li Jian The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, 100730, Beijing, People's Republic of China aut International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 307-315 1573-3149 17:4<307 2011 17 10989 https://doi.org/10.1007/s10989-011-9269-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10989-011-9269-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Lanfang Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Li Fang Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Li Feng Department of Physiology, Hunan College of Traditional Chinese Medicine, 410007, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Mao Xiaohuan Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Yang Li Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Huang Hao Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Guo Yu Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Chen Linxi Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, 421001, Hengyang, People's Republic of China aut NATIONALLICENCE 700 1- Li Jian The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, 100730, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 307-315 1573-3149 17:4<307 2011 17 10989 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer