Endoplasmic reticulum stress is involved in myocardial apoptosis of streptozocin-induced diabetic rats.
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 NH(2)-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.
Li
Zhenhua
Z
Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education and Ministry of Health, Jinan 250012, China.
Zhang
Tao
T
Dai
Hongyan
H
Liu
Guanghui
G
Wang
Haibin
H
Sun
Yingying
Y
Zhang
Yun
Y
Ge
Zhiming
Z
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology*; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000502:physiology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
D053454:Caspase 12; D006360:Heat-Shock Proteins; D048055:Mitogen-Activated Protein Kinase 8; D018832:Molecular Chaperones; D051742:Transcription Factor CHOP; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat