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Involvement of endoplasmic reticulum stress in myocardial apoptosis of streptozocin-induced diabetic rats.

Li Z, Zhang T, Dai H, Liu G, Wang H, Sun Y, Zhang Y, Ge Z - J Clin Biochem Nutr (2007)

Bottom Line: We performed immunohistochemistry, Western blot and real time PCR to analysis two hallmarks of ERS, glucose regulated protein78 (Grp78) and Caspase12.We found both Grp78 and Caspase12 had enhanced expression in protein and mRNA levels in diabetic myocardium than normal rat's, and Caspase12 was activated in diabetic heart.Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis took part in the pathophysiology of diabetic cardiomyopathy.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
Apoptosis plays critical role in diabetic cardiomyopathy and endoplasmic reticulum stress (ERS) is one of intrinsic apoptosis pathways. For previous studies have shown that endoplasmic reticulum become swell in diabetic myocardium and ERS was involved in diabetes mellitus and heart failure, this study aimed to demonstrate whether ERS was induced in myocardium of streptozocin (STZ)-induced diabetic rats. We established type 1 diabetic rat model with STZ intraperitoneal injection, 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 analysis two hallmarks of ERS, glucose regulated protein78 (Grp78) and Caspase12. We found both Grp78 and Caspase12 had enhanced expression in protein and mRNA levels in diabetic myocardium than normal rat's, and Caspase12 was activated in diabetic heart. Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis took part in the pathophysiology of diabetic cardiomyopathy.

No MeSH data available.


Related in: MedlinePlus

A, B: The normal (A) and diabetic (B) myocardium were stained with haematoxylin-eosin, diabetic cardiac muscle fibers were disorder and many of them were collapsed, diabetic myocardium showed fibrosis and extensive focal coalescent areas of ischemic myocyte degeneration in the subendocardial, subepicardial region and papillary muscles of the myocardium.C, D, E: Diabetic heart (E) showed more TUNEL-positive cardiocytes and endothelial cells than normal (D) heart (p<0.05). C was negative control.F, G, H, I, J, K, L, M, N: Immunoreactive Grp78 and Caspase12 of sections from diabetic heart (H: Grp78; K: Caspase12) and normal heart (G: Grp78; J: Caspase12) were shown. The diabetic heart showed strong immunoreactivity for Grp78 (p<0.05) and Caspase12 (p<0.05). F (Grp78) and I (Caspase12) were negative control. Bar = 50 µm.
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Figure 2: A, B: The normal (A) and diabetic (B) myocardium were stained with haematoxylin-eosin, diabetic cardiac muscle fibers were disorder and many of them were collapsed, diabetic myocardium showed fibrosis and extensive focal coalescent areas of ischemic myocyte degeneration in the subendocardial, subepicardial region and papillary muscles of the myocardium.C, D, E: Diabetic heart (E) showed more TUNEL-positive cardiocytes and endothelial cells than normal (D) heart (p<0.05). C was negative control.F, G, H, I, J, K, L, M, N: Immunoreactive Grp78 and Caspase12 of sections from diabetic heart (H: Grp78; K: Caspase12) and normal heart (G: Grp78; J: Caspase12) were shown. The diabetic heart showed strong immunoreactivity for Grp78 (p<0.05) and Caspase12 (p<0.05). F (Grp78) and I (Caspase12) were negative control. Bar = 50 µm.

Mentions: With hematoxylin-eosin and TUNEL staining, the characteristics of diabetic cardiomyopathy and more apoptotic cardiocytes and endothelial cells were found in diabetic group. Correspondingly, the two ERS hallmarks, Grp78 and Caspase12, in the diabetic heart showed strong immunoreactivity than normal group. (Fig. 2 A–N)


Involvement of endoplasmic reticulum stress in myocardial apoptosis of streptozocin-induced diabetic rats.

Li Z, Zhang T, Dai H, Liu G, Wang H, Sun Y, Zhang Y, Ge Z - J Clin Biochem Nutr (2007)

A, B: The normal (A) and diabetic (B) myocardium were stained with haematoxylin-eosin, diabetic cardiac muscle fibers were disorder and many of them were collapsed, diabetic myocardium showed fibrosis and extensive focal coalescent areas of ischemic myocyte degeneration in the subendocardial, subepicardial region and papillary muscles of the myocardium.C, D, E: Diabetic heart (E) showed more TUNEL-positive cardiocytes and endothelial cells than normal (D) heart (p<0.05). C was negative control.F, G, H, I, J, K, L, M, N: Immunoreactive Grp78 and Caspase12 of sections from diabetic heart (H: Grp78; K: Caspase12) and normal heart (G: Grp78; J: Caspase12) were shown. The diabetic heart showed strong immunoreactivity for Grp78 (p<0.05) and Caspase12 (p<0.05). F (Grp78) and I (Caspase12) were negative control. Bar = 50 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: A, B: The normal (A) and diabetic (B) myocardium were stained with haematoxylin-eosin, diabetic cardiac muscle fibers were disorder and many of them were collapsed, diabetic myocardium showed fibrosis and extensive focal coalescent areas of ischemic myocyte degeneration in the subendocardial, subepicardial region and papillary muscles of the myocardium.C, D, E: Diabetic heart (E) showed more TUNEL-positive cardiocytes and endothelial cells than normal (D) heart (p<0.05). C was negative control.F, G, H, I, J, K, L, M, N: Immunoreactive Grp78 and Caspase12 of sections from diabetic heart (H: Grp78; K: Caspase12) and normal heart (G: Grp78; J: Caspase12) were shown. The diabetic heart showed strong immunoreactivity for Grp78 (p<0.05) and Caspase12 (p<0.05). F (Grp78) and I (Caspase12) were negative control. Bar = 50 µm.
Mentions: With hematoxylin-eosin and TUNEL staining, the characteristics of diabetic cardiomyopathy and more apoptotic cardiocytes and endothelial cells were found in diabetic group. Correspondingly, the two ERS hallmarks, Grp78 and Caspase12, in the diabetic heart showed strong immunoreactivity than normal group. (Fig. 2 A–N)

Bottom Line: We performed immunohistochemistry, Western blot and real time PCR to analysis two hallmarks of ERS, glucose regulated protein78 (Grp78) and Caspase12.We found both Grp78 and Caspase12 had enhanced expression in protein and mRNA levels in diabetic myocardium than normal rat's, and Caspase12 was activated in diabetic heart.Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis took part in the pathophysiology of diabetic cardiomyopathy.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
Apoptosis plays critical role in diabetic cardiomyopathy and endoplasmic reticulum stress (ERS) is one of intrinsic apoptosis pathways. For previous studies have shown that endoplasmic reticulum become swell in diabetic myocardium and ERS was involved in diabetes mellitus and heart failure, this study aimed to demonstrate whether ERS was induced in myocardium of streptozocin (STZ)-induced diabetic rats. We established type 1 diabetic rat model with STZ intraperitoneal injection, 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 analysis two hallmarks of ERS, glucose regulated protein78 (Grp78) and Caspase12. We found both Grp78 and Caspase12 had enhanced expression in protein and mRNA levels in diabetic myocardium than normal rat's, and Caspase12 was activated in diabetic heart. Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis took part in the pathophysiology of diabetic cardiomyopathy.

No MeSH data available.


Related in: MedlinePlus