S Cao1, B Yan2, Y Lu2, G Zhang1, J Li1, W Guo1, Y Zhao3, S Zhang4. 1. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 2. Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 3. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 4. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: shuijunzhangzzu@gmail.com.
Abstract
BACKGROUND: C/EBP homologous protein (CHOP) is an important marker in endoplasmic reticulum stress (ERS)-associated cell apoptosis. The role of CHOP-induced renal apoptosis remains unclear in rats with brain death (BD). The present study aims to investigate the possible implication of CHOP-mediated, ERS-related BD-induced apoptosis in rats. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided randomly into 4 experimental groups. We examined activation of ERS and apoptosis-related protein expression using Western blot and immunohistochemical staining. In addition, apoptosis is assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay. RESULTS: Kidneys harvested after BD show increased ERS- and apoptosis-related protein markers compared with kidneys of non-BD rats. Salubrinal (Sal) significantly increased levels of p-eIF2a and decreased the activity of CHOP at 6 hours after BD compared with vehicle-treated dimethylsulfoxide. CONCLUSIONS: Treating the BD donor with Sal influences renal apoptosis compared with vehicle-treated BD rats. Our results indicate that targeting the CHOP pathway provides a promising therapeutic approach for kidney injury associated with donor BD.
BACKGROUND:C/EBP homologous protein (CHOP) is an important marker in endoplasmic reticulum stress (ERS)-associated cell apoptosis. The role of CHOP-induced renal apoptosis remains unclear in rats with brain death (BD). The present study aims to investigate the possible implication of CHOP-mediated, ERS-related BD-induced apoptosis in rats. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided randomly into 4 experimental groups. We examined activation of ERS and apoptosis-related protein expression using Western blot and immunohistochemical staining. In addition, apoptosis is assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay. RESULTS: Kidneys harvested after BD show increased ERS- and apoptosis-related protein markers compared with kidneys of non-BD rats. Salubrinal (Sal) significantly increased levels of p-eIF2a and decreased the activity of CHOP at 6 hours after BD compared with vehicle-treated dimethylsulfoxide. CONCLUSIONS: Treating the BD donor with Sal influences renal apoptosis compared with vehicle-treated BD rats. Our results indicate that targeting the CHOP pathway provides a promising therapeutic approach for kidney injury associated with donor BD.