Jing Lu1, Qi-Ming Dai1, Gen-Shan Ma1, Yue-Hong Zhu1, Bing Chen1, Bing Li1, Yu-Yu Yao2. 1. Department and Institute of Cardiology, Zhongda Hospital, Medical School of Southeast University, No. 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China. 2. Department and Institute of Cardiology, Zhongda Hospital, Medical School of Southeast University, No. 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China. yaoyuyunj@hotmail.com.
Abstract
PURPOSE: Enhanced endoplasmic reticulum (ER) stress and down-regulated SERCA2a expression play crucial roles in diabetes. We aimed to verify whether erythropoietin (EPO) attenuates cardiac dysfunction by suppressing ER stress in diabetic rats. METHODS: Forty male SD rats were randomly divided into four groups: control, EPO-treated control, vehicle-treated diabetic, and EPO-treated diabetic groups. The animals in the EPO-treated control and diabetic groups were administered recombinant human EPO (1000 U/kg body weight) once per week for 12 weeks. RT-PCR and Western blotting assays were performed to detect the expression of 78-kDa glucose-regulated protein precursor (GRP78) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a). We cultured neonatal rat cardiomyocytes and investigated the protective effects of EPO against high glucose (HG)-induced apoptosis. Intracellular calcium levels were measured through confocal microscopy. RESULTS: We observed increased myocardial GRP78 expression and decreased myocardial SERCA2a expression in diabetic rats. EPO prevented the changes in GRP78, SERCA2a expression and cardiac dysfunction in diabetic rats. The levels of GRP78 protein were significantly reduced in EPO-treated diabetic rats compared with vehicle-treated diabetic rats (GRP78 protein 0.09 ± 0.03 vs. 0.54 ± 0.04, P < 0.01). The levels of the SERCA2a proteins were significantly increased in EPO-treated diabetic rats compared with vehicle-treated diabetic rats (SERCA2a protein 0.60 ± 0.05 vs. 0.13 ± 0.04, P < 0.01). A reduction in apoptosis was observed in the cardiomyocytes treated with 20 U/mL EPO compared with the cardiomyocytes cultured under HG conditions (apoptosis rate 18.9 ± 1.94 vs. 37.9 ± 1.59%, P < 0.01). CONCLUSIONS: This study demonstrates that EPO treatment improved the parameters of cardiac function following HG-induced injury by suppressing ER stress and inducing SERCA2a expression.
PURPOSE: Enhanced endoplasmic reticulum (ER) stress and down-regulated SERCA2a expression play crucial roles in diabetes. We aimed to verify whether erythropoietin (EPO) attenuates cardiac dysfunction by suppressing ER stress in diabeticrats. METHODS: Forty male SD rats were randomly divided into four groups: control, EPO-treated control, vehicle-treated diabetic, and EPO-treated diabetic groups. The animals in the EPO-treated control and diabetic groups were administered recombinant humanEPO (1000 U/kg body weight) once per week for 12 weeks. RT-PCR and Western blotting assays were performed to detect the expression of 78-kDa glucose-regulated protein precursor (GRP78) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a). We cultured neonatal rat cardiomyocytes and investigated the protective effects of EPO against high glucose (HG)-induced apoptosis. Intracellular calcium levels were measured through confocal microscopy. RESULTS: We observed increased myocardial GRP78 expression and decreased myocardial SERCA2a expression in diabeticrats. EPO prevented the changes in GRP78, SERCA2a expression and cardiac dysfunction in diabeticrats. The levels of GRP78 protein were significantly reduced in EPO-treated diabeticrats compared with vehicle-treated diabeticrats (GRP78 protein 0.09 ± 0.03 vs. 0.54 ± 0.04, P < 0.01). The levels of the SERCA2a proteins were significantly increased in EPO-treated diabeticrats compared with vehicle-treated diabeticrats (SERCA2a protein 0.60 ± 0.05 vs. 0.13 ± 0.04, P < 0.01). A reduction in apoptosis was observed in the cardiomyocytes treated with 20 U/mL EPO compared with the cardiomyocytes cultured under HG conditions (apoptosis rate 18.9 ± 1.94 vs. 37.9 ± 1.59%, P < 0.01). CONCLUSIONS: This study demonstrates that EPO treatment improved the parameters of cardiac function following HG-induced injury by suppressing ER stress and inducing SERCA2a expression.
Authors: Lauren L Jantzie; Akosua Y Oppong; Fatu S Conteh; Tracylyn R Yellowhair; Joshua Kim; Gabrielle Fink; Adam R Wolin; Frances J Northington; Shenandoah Robinson Journal: Front Neurol Date: 2018-04-13 Impact factor: 4.003
Authors: Kirsten T Nijholt; Laura M G Meems; Willem P T Ruifrok; Alexander H Maass; Salva R Yurista; Mario G Pavez-Giani; Belend Mahmoud; Anouk H G Wolters; Dirk J van Veldhuisen; Wiek H van Gilst; Herman H W Silljé; Rudolf A de Boer; B Daan Westenbrink Journal: Pflugers Arch Date: 2021-06-17 Impact factor: 3.657