Dung-Shen Downregulates the Synergistic Apoptotic Effects of Angiotensin II Plus Leu 27-IGF II on Cardiomyoblasts.
BACKGROUND
Insulin growth factor II (IGFII) is expressed after ischemic stress in pig hearts and after myocardial infarction in humans. However, its receptor (IGFIIR) cannot be found in normal adult hearts. Moreover, a mouse IGFII overexpression model showed a heart and kidney hypertrophy phenomenon similar to Beckwith-Wiedemann syndrome in humans. The previous studies from our lab showed that an increase in AngII in H9c2 cells causes an elevation in IGFII and IGFIIR through MEK and JNK activation, leading to a rise in intracellular Ca(2+) ions, activation of calcineurin by PLC-β3 via Gαq, insertion into mitochondrial membranes of BAD, and apoptosis via activation of caspases 9 and 3. Codonopsis pilosula (Dung-shen) has various uses in traditional Chinese medicine, including lowering blood pressure, and increasing red and white blood cell counts.


METHODS
The purpose of our study is to investigate whether the addition of C. pilosula will attenuate the AngII plus Leu27-IGFII-induced apoptosis in H9c2 cardiomyoblast cells.


RESULTS
From MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-tetrazolium bromide] results, it was revealed that AngII plus Leu(27)-IGFII significantly reduced cell viability, which was reversed by C. pilosula. Additionally, C. pilosula also reversed apoptosis (TUNEL staining) increased by AngII plus Leu27-IGFII. Up-regulation of caspase 3 by AngII plus Leu27-IGFII was attenuated by C. pilosula treatment, as shown in western blotting assay and immunofluorescence microscopy results.


CONCLUSIONS
C. pilosula is able to suppress the apoptotic pathway enhanced by AngII plus Leu27-IGFII in myocardial cells.


BACKGROUND
Angiotensin II; Apoptosis; Codonopsis pilosula; Leucine27-insulin like growth factor II; Mitochondrial outer membrane permeability.
Section of Cardiology, Yuan Rung Hospital, Yunlin, Taiwan;
Ko-Shih
KS
Chang
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;
Nien-Hung
NH
Lee
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;
Wei-Wen
WW
Kuo
Division of Cardiology, Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan; ; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;
Wei-Syun
WS
Hu
Section of Cardiology, Yuan Rung Hospital, Yunlin, Taiwan;
Mu-Hsin
MH
Chang
Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;
Fuu-Jen
FJ
Tsai
Department of Emergency Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan; ; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan;
Kun-Hsi
KH
Tsai
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan;
Yuh-Shyong
YS
Yang
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;
Tung-Sheng
TS
Chen
Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; ; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; ; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Chih-Yang
CY
Huang