Cardiac apoptosis induced under high glucose condition involves activation of IGF2R signaling in H9c2 cardiomyoblasts and streptozotocin-induced diabetic rat hearts

Chih Chung Feng, Sudhir Pandey, Ching Yuang Lin, Chia Yao Shen, Ruey Lin Chang, Tung Ti Chang, Ray Jade Chen, Vijaya Padma Viswanadha, Yueh Min Lin, Chih Yang Huang

研究成果: 雜誌貢獻文章

7 引文 斯高帕斯(Scopus)

摘要

The insulin-like growth factor type 2 receptor (IGF2R) overexpression has been implicated in heart disease progression. Unregulated IGF2R signaling triggers cardiac hypertrophy, apoptosis, and cardiomyopathies. The present study investigated the role of IGF2R in cardiomyocyte apoptosis under high glucose (HG) levels and in streptozotocin (STZ) induced diabetic rat hearts. We found that IGF2 and IGF2R protein expression were highly upregulated under high glucose condition in H9c2 cells as well as in STZ induced diabetic rat hearts. Using immunoblotting and TUNEL assay, we found that elevated glucose condition induced IGF2R expression leads to activation of Gαq mediated calcineurin-dependent signaling pathway, which further leads to downstream activation and expression of cardiac hypertrophy related proteins, ANP and BNP. Further, we found that glucose-induced IGF2R expression downregulated survival protein p-Akt, p-Bad (Ser 155) and enhanced the expression of apoptosis-inducing proteins cytochrome c and cleaved Caspase-3. Our results suggested that hyperglycemic condition leads to cellular cardiomyocyte apoptosis both in vitro and in vivo models, via abnormally increased activation of the IGF2R signaling pathway.
原文英語
頁(從 - 到)880-885
頁數6
期刊Biomedicine and Pharmacotherapy
97
DOIs
出版狀態已發佈 - 一月 1 2018

    指紋

ASJC Scopus subject areas

  • Pharmacology

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