Isoproterenol Inhibits Angiotensin II-Stimulated Proliferation and Reactive Oxygen Species Production in Vascular Smooth Muscle Cells through Heme Oxygenase-1
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概要
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Heme oxygenase (HO)-1 is a well-known cytoprotectant against oxidative stress and exhibits an antiproliferative effect in vascular smooth muscle cells (VSMCs). The purpose of the present study was to test whether isoproterenol, one of the synthetic catecholamines having β-adrenergic activity, affected angiotensin II (Ang II)-induced cell proliferation and reactive oxygen species (ROS) production. Also, the presumptive underlying signaling pathways in VSMCs were studied. Aortic VSMCs from 11-week-old male Sprague-Dawley rats were used. Isoproterenol dose-dependently increased HO-1 expression through β2-adrenoceptor (AR) and protein kinase A (PKA) pathway, and isoproterenol concentration-dependently increased β2-AR mRNA expression. Isoproterenol attenuated Ang II-induced cell proliferation, as evidenced by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. This effect of isoproterenol was inhibited by pretreatment of the cells with β2-AR antagonist butoxamine, PKA inhibitor H-89 and HO inhibitor Tin Protoporphyrin IX (SnPP IX), respectively. Isoproterenol inhibited phosphorylation level of Ang II-induced extracellular signal-regulated kinase (ERK1/2). Isoproterenol significantly inhibited Ang II-induced ROS production through the ERK1/2 pathway. These findings suggest that isoproterenol, via induction of HO-1, inhibits Ang II-stimulated proliferation and ROS production in cultured VSMCs.
- 公益社団法人 日本薬学会の論文
著者
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KIM Jung
Department of Occupational Medicine, College of Medicine, Dong-A University
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LEE Kwang
Department of Sericulture and Entomology, National Institute of Agriculture and Technology
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Kang Young
Department Of Electrical And Electronic Engineering Tokyo Institute Of Technology
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Choi Hyoung
Department of Pharmacology, Aging-associated Vascular Disease Research Center, College of Medicine,
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Kim Jung
Department Of Applied Chemistry School Of Engineering The University Of Tokyo
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Choi Hyoung
Department Of Herbal Pharmacology Graduate School Of East-west Medical Science Kyung Hee University
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Lee Kwang
Department Of Bioengineering Yonsei University
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Kang Young
Department Of Chemistry Sogang University
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Kang Young
Department Of Chemistry Chungbuk National University
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Kim Jung
Department Of Applied Bioscience Cha University
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Kim Jung
Department of Pharmacology, College of Medicine, Yeungnam University
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LEE Kwang
Department of Pharmacology, College of Medicine, Yeungnam University
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Choi Hyoung
Department of Pharmacology, College of Medicine, Yeungnam University
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Lee Kwang
Department of Advanced Technology Fusion (DATF), Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea
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