Endoplasmic reticulum stress is involved in myocardial apoptosis of streptozocin-induced diabetic rats

• DOI: 10.1677/joe-07-0230
• Publication Date: 2008-02-29T18:52:07Z
• Authors: Zhenhua Li; Tao Zhang; Hongyan Dai; Guanghui Liu; Haibin Wang; Yingying Sun; Yun Zhang; Zhiming Ge
• Keywords: Male; Reverse Transcriptase Polymerase Chain Reaction; Myocardium; Apoptosis; Endoplasmic Reticulum; Immunohistochemistry; Diabetes Mellitus, Experimental; Rats; 3. Good health; Diabetes Complications; Disease Models, Animal; Stress, Physiological; In Situ Nick-End Labeling; Animals; Mitogen-Activated Protein Kinase 8; Rats, Wistar; Cardiomyopathies; Caspase 12; Heat-Shock Proteins; Transcription Factor CHOP; Molecular Chaperones

Apoptosis plays a critical role in the diabetic cardiomyopathy, and endoplasmic reticulum stress (ERS) is one of the intrinsic apoptosis pathways. Previous studies have shown that the endoplasmic reticulum becomes swollen and dilated in diabetic myocardium, and ERS is involved in heart failure and diabetic kidney. This study is aimed to demonstrate whether ERS is induced in myocardium of streptozotocin (STZ)-induced diabetic rats. We established a type 1 diabetic rat model, used echocardiographic evaluation, hematoxylin–eosin staining, and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify the existence of diabetic cardiomyopathy and enhanced apoptosis in the diabetic heart. We performed immunohistochemistry, western blot, and real-time PCR to analyze the hallmarks of ERS that include glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase12. We found these hallmarks to have enhanced expression in protein and mRNA levels in diabetic myocardium. Also, another pathway that can lead to cell death of ERS, c-Jun NH2-terminal kinase-dependent pathway, was also activated in diabetic heart. Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis occurred in the pathophysiology of diabetic cardiomyopathy.