IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Gq interaction and protein kinase Cα-/CaMKII activation in H9c2 cardiomyoblast cells

Chun Hsien Chu, Bor Show Tzang, Li Mien Chen, Chia Hua Kuo, Yi Chang Cheng, Ling Yun Chen, Fuu Jen Tsai, Chang Hai Tsai, Wei Wen Kuo, Chih Yang Huang

研究成果: Article同行評審

70 引文 斯高帕斯(Scopus)

摘要

The role played by IGF-II in signal transduction through the IGF-II/ mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. In our previous studies, we detected an increased expression of IGF-II and IGF2R in cardiomyocytes that had undergone pathological hypertrophy. We hypothesized that after binding with IGF-II, IGF2R may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. In this study, we used immunohistochemical analysis of the human cardiovascular tissue array to detect expression of IGF2R. In our study of H9c2 cardiornyoblast cell cultures, we used the rhodamine phalloidin staining to measure the cell hypertrophy and western blot to measure tho expression of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. We found that a significant association between IGF2R overexpression and myocardial infarction. The treatment of H9c2 cardiomyoblast cells with IGF-II not only induced cell hypertrophy but also increased the protein level of ANP and BNP. Using Leu27IGF-II, an analog of IGF-II which interacts selectively with the IGF2R, to specifically activate IGF2R signaling cascades, we found that binding of Leu27IGF-II to IGF2R led to an increase in the phosphorylation of protein Kinase II (PKC)-α and calcium/calmodulin-dependent protein kinase 11 (CaMKII) in a Gαq-dependent manner. By the inhibition of PKC-α/CaMKII activity, we found that IGF-II and Leu27IGF-II-induced cell hypertrophy and upregulation of ANP and BNP were significantly suppressed. Taken together, this study provides a new insight into the effects of the IGF2R and its downstream signaling in cardiac hypertrophy. The suppression of IGF2R signaling pathways may be a good strategy to prevent the progression of pathological hypertrophy.

原文English
頁(從 - 到)381-390
頁數10
期刊Journal of Endocrinology
197
發行號2
DOIs
出版狀態Published - 2008 五月

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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