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

Abstract

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.

Involvement of endoplasmic reticulum stress in adenosine-induced human hepatoma HepG2 cell apoptosis

“…On the other hand, cells can up-regulate the expression of GRP78 to decrease the dissociation and activation. It has been reported that the expression of GRP78 increases in ers-induced apoptosis (17,20). In the present study, we also observed the expression of GRP78 increased (Fig.…”

“…ers-induced apoptosis has been implicated in several diseases such as diabetes mellitus, parkinson's disease (15) and has been demonstrated in some tumor cell lines such as pc-12 neuronal cells (16) and lung carcinoma A-549 cells (17). Some drugs, ischemia-reperfusion, hypoxia and glucose starvation can disturb er function and may lead to ers (18)(19)(20). ERS initiates the unfolded protein response (UPR), which alleviates protein overload in the er (21).…”

Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a

“…It is unclear whether this effect extends to hyperglycemiainduced cardiomyocyte apoptosis. Hyperglycemia-induced cardiomyocyte apoptosis is associated with increased reactive oxygen species (ROS) production and subsequent endoplasmic reticulum (ER) stress (27,59). ER stress activates the unfolded protein response (UPR), a set of signaling pathways that halt cellular processes such as protein translation and that upregulate expression of chaperone proteins to restore normal ER function.…”

Hydrogen sulfide exhibits cardioprotective effects by decreasing endoplasmic reticulum stress in a diabetic cardiomyopathy rat model

“…Cellular metabolic abnormalities and defections of organelles were shown to participate in the pathology of DC (10)(11)(12)(13)(14), which is a chronic and complex process associated with impaired calcium homeostasis, increased lipid uptake, myocardial insulin resistance, glucotoxicity, increased oxidative stress and activation of the renin-angiotensin system (15). Furthermore, the pathological role of endoplasmic reticulum (ER) stress in DC has been noted in a number of studies (16)(17)(18).…”