Dung-shen (Codonopsis pilosula) attenuated the cardiac-impaired insulin-like growth factor II receptor pathway on myocardial cells

Previous studies from our lab showed that increase in AngIl in H9c2 cells causes elevated IGFII and IGFIIR through MEK and JNK, leading to rise in intracellular calcium, calcineurin activation by PLC-beta 3 via G alpha q, 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 Leu(27)-IGFII-induced calcium influx and apoptosis in H9c2 cardiomyoblasts. C pilosula significantly attenuated AngII induced IGFIIR promoter activity. Leu(27)-IGFII was applied to enhance the Angll effect. C pilosula also reversed Ca2+ influx, MOMP and apoptosis increased by AngIl plus Leu(27)-IGFIL Molecular markers in IGFIIR apoptotic pathway (IGFIIR, calcineurin, etc.) and IGFIIR-G alpha q association were downregulated by C pilosula. However, p-Bad(Ser136) and BcI-2 were increased. Therefore, C pilosula suppresses Angll plus Leu(27)-IGFII-induced IGFII/IGFIIR pathway in myocardial cells. (C) 2012 Elsevier Ltd. All rights reserved.