Erythropoietin Attenuates Cardiac Dysfunction in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Diabetic Cardiomyopathy
- 04.08.2017
- ORIGINAL ARTICLE
Erschienen in:
- Verfasst von
- Jing Lu
- Qi-ming Dai
- Gen-shan Ma
- Yue-hong Zhu
- Bing Chen
- Bing Li
- Yu-yu Yao
- Erschienen in
- Cardiovascular Drugs and Therapy | Ausgabe 4/2017
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.
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- Titel
- Erythropoietin Attenuates Cardiac Dysfunction in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Diabetic Cardiomyopathy
- Verfasst von
-
Jing Lu
Qi-ming Dai
Gen-shan Ma
Yue-hong Zhu
Bing Chen
Bing Li
Yu-yu Yao
- Publikationsdatum
- 04.08.2017
- Verlag
- Springer US
- Erschienen in
-
Cardiovascular Drugs and Therapy / Ausgabe 4/2017
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241 - DOI
- https://doi.org/10.1007/s10557-017-6742-1
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