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

Abstract

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.

• Authors: 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
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 97 Pg. 880-885 (Jan 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29136764 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Igf2 protein, rat
• Receptor, IGF Type 2
• Streptozocin
• Insulin-Like Growth Factor II
• Caspase 3
• Glucose

Topics

• Animals
• Apoptosis (physiology)
• Cardiomegaly (physiopathology)
• Caspase 3 (metabolism)
• Cell Line
• Diabetes Mellitus, Experimental (physiopathology)
• Down-Regulation
• Glucose (metabolism)
• Hyperglycemia (complications)
• In Situ Nick-End Labeling
• Insulin-Like Growth Factor II (genetics, metabolism)
• Male
• Myocytes, Cardiac (pathology)
• Rats
• Rats, Wistar
• Receptor, IGF Type 2 (genetics, metabolism)
• Signal Transduction
• Streptozocin
• Up-Regulation