Dung-shen (Codonopsis pilosula) attenuated the
Cardiac-impaired Insulin-like Growth Factor II Receptor
Pathway on Myocardial Cells
Wei-Syun Hu1,2, Nien-Hung Lee 3, Chen-Yen Tsai4, Mu-Hsin Chang5, Gwo-Ping Jong5, Chia-Hua Kuo6, Bor-Show Tzang7, Fuu-Jen Tsai8, Chang-Hai Tsai9 and Chih-Yang Huang3,8,10
胡緯勳1,2
, 李念鴻3, 蔡成諺4, 張木信5, 鐘國屏5, 郭家譁6, 曾柏修7, 蔡輔仁8, 蔡長海9, 黃志 揚3,8, 10
1
Division of Cardiology, Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan
2
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan 4
Departments of Pediatrics, China Medical University Beigang Hospital, Yunlin, Taiwan 5
Division of Cardiology, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan
6
Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei, Taiwan 7
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan 8
Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
9
Department of Healthcare Administration, Asia University,Taichung, Taiwan 10
Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
Abstract
Previous studies from our lab showed that increase in AngII in H9c2 cells causes elevated IGFII and IGFIIR through MEK and JNK, leading to rise in intracellular calcium, calcineurin activation by PLC-β3 via Gαq, insertion into mitochondrial membranes of Bad, and apoptosis via caspases 9 and 3.
Codonopsis pilosula is traditionally used to lower blood pressure. The purpose of our study is to
investigate if C. pilosula attenuates AngII plus Leu27-IGFII-induced calcium influx and apoptosis in H9c2 cardiomyoblasts. C. pilosula significantly attenuated AngII induced IGFIIR promoter activity. Leu27-IGFII was applied to enhance the AngII effect. C. pilosula also reversed Ca2+ influx, MOMP and apoptosis increased by AngII plus Leu27-IGFII. Molecular markers in IGFIIR apoptotic pathway (IGFIIR, calcineurin, etc.) and IGFIIR-Gαq association were downregulated by C. pilosula. However, p-BadSer136
and Bcl-2 were increased. Therefore, C. pilosula suppresses AngII plus Leu27-IGFII-induced IGFII/IGFIIR pathway in myocardial cells.
Key words: angiotensin II, apoptosis, calcium influx, Codonopsis pilosula, leucine27-insulin like growth factor II, mitochondrial outer-membrane permeability
