Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease.
Endoplasmic reticulum stress has been suggested to play a crucial role in the pathogenesis of diabetic complications. However, whether it is involved in the renal injury of diabetic nephropathy is still not known. We investigated the involvement of ER-associated apoptosis in kidney disease of streptozocin (STZ)-induced diabetic rats. We used albuminuria examination, hematoxylin & eosin (H&E) staining and TUNEL analysis to identify the existence of diabetic nephropathy and enhanced apoptosis. We performed immunohistochemistry, Western blot, and real-time PCR to analyze indicators of ER molecule chaperone and ER-associated apoptosis. GRP78, the ER chaperone, was up-regulated significantly in diabetic kidney compared to control. Furthermore, three hallmarks of ER-associated apoptosis, C/EBP homologous protein (CHOP), c-JUN NH2-terminal kinase (JNK) and caspase-12, were found to have activated in the diabetic kidney. Taken together, those results suggested that apoptosis induced by ER stress occurred in diabetic kidney, which may contribute to the development of diabetic nephropathy.
Liu
Guanghui
G
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Sun
Yingying
Y
Li
Zhenhua
Z
Song
Tao
T
Wang
Haibin
H
Zhang
Yun
Y
Ge
Zhiming
Z
D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP