Abstract |
Hyperglycemia-induced reactive oxygen species (ROS) generation and Ca(2+) overload contribute to the development of diabetic cardiomyopathy. In this study, we aimed to study the protective effects of Chikusetsu saponin IVa (CHS) from Aralia taibaiensis against hyperglycemia-induced myocardial injuries. Treatment of H9c2 cells with high glucose (HG) for 24 h resulted in a loss of cell viability and increase of ROS, LDH and Ca(2+) levels, and also induced cell apoptosis, and those changes were all markedly reversed by the administration of CHS. In further studies, CHS dose-dependently increased the expression of Homer1a, ERK1/2 and SIRT1 in both H9c2 cells and rat primary cardiomyocytes. However, transfection of Homer1a-specific siRNA abolished the ability of CHS in controlling the ROS and Ca(2+) homeostasis. Moreover, specific SIRT1 inhibitors or siRNA significantly suppressed the enhanced phosphorylation of ERK1/2 and expression of Homer1a induced by CHS as well as its cytoprotective effect. CHS induced Homer1a expression was also suppressed by siERK1/2. Additionally, results in diabetic mice also showed that CHS protected myocardium from I/R-introduced apoptosis by activating the SIRT1/ERK1/2/Homer1a pathway. These results demonstrated that CHS protected against hyperglycemia-induced myocardial injury through SIRT1/ERK1/2 and Homer1a pathway in vivo and in vitro.
|
Authors | Jialin Duan, Ying Yin, Guo Wei, Jia Cui, Enhu Zhang, Yue Guan, Jiajia Yan, Chao Guo, Yanrong Zhu, Fei Mu, Yan Weng, Yanhua Wang, Xiaoxiao Wu, Miaomiao Xi, Aidong Wen |
Journal | Scientific reports
(Sci Rep)
Vol. 5
Pg. 18123
(Dec 09 2015)
ISSN: 2045-2322 [Electronic] England |
PMID | 26648253
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cardiotonic Agents
- Reactive Oxygen Species
- Saponins
- chikusetsu saponin IVa
- Oleanolic Acid
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Sirtuin 1
- Glucose
- Calcium
|
Topics |
- Animals
- Apoptosis
(drug effects)
- Calcium
(metabolism)
- Cardiotonic Agents
(pharmacology)
- Cardiotoxicity
- Glucose
(metabolism, toxicity)
- Male
- Mice
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Myoblasts, Cardiac
(drug effects, metabolism)
- Myocytes, Cardiac
(drug effects, metabolism)
- Oleanolic Acid
(analogs & derivatives, pharmacology)
- Oxidative Stress
(drug effects)
- Rats
- Reactive Oxygen Species
(metabolism)
- Saponins
(pharmacology)
- Signal Transduction
(drug effects)
- Sirtuin 1
(metabolism)
|