Exp Mol Med.
2007 Feb;39(1):65-73.
Sodium tanshinone IIA sulfonate depresses angiotensin II-induced cardiomyocyte hypertrophy through MEK/ERK pathway
- Affiliations
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- 1Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, P.R.China. lqstjmu@yahoo.com.cn
- 2Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, P.R.China.
- 3School of Medicine and Health Administration, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, P.R.China.
Abstract
- Cardiomyocyte hypertrophy is a major cause of morbidity and mortality worldwide. The aim of this study is to determine the effects of sodium tanshinone IIA sulfonate (STS) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) in vivo and in vitro. In long-term treatment, adult Wistar rats were infused with Ang II for three weeks via osmotic mini-pumps and some of them were given intragastrically of STS. Left ventricle was isolated; the ratio of left ventricular weight to body weight and systolic blood pressure (SBP) were determined and heart morphometry was assessed after hematoxylin and eosin staining. Results indicated STS inhibited Ang II-induced increases in myocyte diameter and decreased the LVW/BW ratio independent of decreasing systolic blood pressure. In vitro, treatment of cultured cardiomyocytes with STS inhibited Ang II-induced increase in cell size, protein synthesis, ANP expression, activation of extracellular signal-regulated kinase (ERK) and ERK kinase (MEK). Then we reexamined the mechanism of STS-induced anti-hypertrophic effects. Results revealed MEK inhibitor U0126 (20 microM) markedly enhanced STS-induced depressions in [3H]leucine incorporation and ANP expression. In conclusion, MEK/ERK pathway plays a significant role in the anti-hypertrophic effects of STS.
Keyword
MeSH Terms
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Rats, Wistar
Rats
Phenanthrenes/chemistry/*pharmacology
Myocytes, Cardiac/*drug effects/enzymology/pathology
Molecular Structure
Mitogen-Activated Protein Kinase Kinases/*metabolism
MAP Kinase Signaling System/*drug effects
Extracellular Signal-Regulated MAP Kinases/*metabolism
Enzyme Activation/drug effects
Cardiomegaly/chemically induced/enzymology/*metabolism/pathology
Animals
Angiotensin II/*antagonists & inhibitors/pharmacology
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