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This Article Full Text Full Text (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.

¹ Trauma and Emergency Center
² School of Medicine, China Medical University Hospital, Taichung 404, Taiwan, ROC
³ Division of Cardiology, Armed Force Taichung General Hospital, Taichung 411, Taiwan, ROC
⁴ Graduate Institute of Chinese Medical Science, China Medical University, Taichung 404, Taiwan, ROC
⁵ School of Applied Chemistry
⁶ Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan, ROC
⁷ Division of Gastroenterology, Department of Internal Medicine, Armed-Force Taichung General Hospital, Taichung 411, Taiwan, ROC
⁸ Department of Pediatrics, Medical Research and Medical Genetics, China Medical University, Taichung 404, Taiwan, ROC
⁹ Department of Healthcare Administration, Asia University, Taichung 413, Taiwan, ROC
¹⁰ Division of Medical Technology, Department of Internal Medicine, Armed-Force Taichung General Hospital, Taichung 411, Taiwan, ROC
¹¹ Graduate Institute of Basic Medical Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC
¹² Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan, ROC

(Correspondence should be addressed to C-H Chu; Email: s210001{at}smail.csmu.edu.tw)

^* (L-M Chen, C-Y Huang and C-H Chu contributed equally to this paper)

This study examines the role of IGF2/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 IGF2 signaling without interfacing with IGFI receptor (IGF1R) after exposure to IGF2. Leu27IGF2, an analog of IGF2 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 IGF1 treatment preventing angiotensin II and AG1024-induced cell apoptosis, Leu27IGF2 appears to synergistically increase apoptosis in those cells. We further found cell apoptosis induction and an increase in the active form of caspase 3 in the treatment of cells with Leu27IGF2, but not IGF1. To detect the interaction between IGF2R and Gq using the immunoprecipitation assay, we found that IGF2R could directly interact with Gq and after treatment with Leu27IGF2 the binding ability of Gq to IGF2R had increased. This sequentially resulted in the phosphorylation of phospholipase C-β, a key downstream modulator of Gq, on serine 537. Moreover, disruption of the Gq protein by small interferon RNA reduced the cell apoptosis induced by Leu27IGF2. 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.