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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0121v1 43/6/221    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, R.-J. Articles by Chu, C.-H. PubMed PubMed Citation Articles by Chen, R.-J. Articles by Chu, C.-H.

R Chen, Trauma and Emergency Center, China Medical University Hospital, Taichung, Taiwan, Province of China
H Wu, Taichung, Taiwan, Province of China
M Chang, Department of Internal Medicine, Armed-Force, Taichung General Hospital, Division of Cardiology, Taichung, Taiwan, Province of China
C Lai, Taichung, Taiwan, Province of China
Y Tien, Taichung, Taiwan, Province of China
J Hwang, School of Applied Chemistry, Chung-Shan Medical University, Taichung, Taiwan, Province of China
W Kuo, Department of Internal Medicine, Armed-Force, Taichung General Hospital, Division of Gastroenterology, Taichung, Tanzania, United Republic of
F Tsai, China Medical University, Department of Pediatrics, Medical Research and Medical Genetics, Taichung, Taiwan, Province of China
C Tsai, Department of Healthcare Administration, Asia University, Taichung, Taiwan, Province of China
L Chen, Department of Internal Medicine, Armed-Force, Taichung General Hospital, Division of Medical Technology, Taichung, Taiwan, Province of China
C Huang, China Medical University, Graduate Institute of Chinese Medical Science, Taichung, Taiwan, Province of China
C Chu, Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Province of China

Correspondence: Ray-Jade Chen, Email: rayjchen{at}www.cmuh.org.tw

Abstract

This study examines the role of IGF-II/mannose 6-phosphate receptor (IGF2R) signaling in the signaling transduction regulation and cell apoptosis in H9c2 cardiomyoblast cells. However, it is difficult to recognize the distinct activation of Insulin like growth factor II (IGF2) signaling without interfacing with Insulin like growth factor I receptor (IGF1R) after exposure to IGF-II. Leu27IGF-II, an analog of IGF-II that interacts selectively with the IGF2R, was used to specifically activate IGF2R signaling in this study. DNA fragmentation and TUNEL assay revealed that in contrast to IGF-I treatment preventing angiotensin II (ANGII) and AG1024-induced cell apoptosis, Leu27IGF-II appears to synergistically increase apoptosis in those cells. We further found cell apoptosis induction and an increase in active-form caspase 3 in the treatment of cells with Leu27IGF-II, but not IGF-I. To detect the interaction between IGF2R and Gq using the immuno-precipitation assay, we found that IGF2R could directly interact with Gq and after treatment with Leu27IGF-II the binding ability of Gq to IGF2R was increased. This sequentially resulted in the phosphorylation of phospholipase C-β (PLC-β), a key downstream modulator of Gq, on serine 537. Moreover, disruption of the Gq protein by siRNA reduced the cell apoptosis induced by Leu27IGF-II. Our findings demonstrate that IGF2R activation appears to induce cell apoptosis via Gq-deriving signaling cascades and its effect is completely different from IGF1R survival signaling.