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Tanshinone IIA inhibits miR-1 expression through p38 MAPK signal pathway in post-infarction rat cardiomyocytes.

Abstract
Tanshinone IIA is a fat-soluble pharmacologically active ingredient of Danshen, a well-known traditional Chinese medicine used for cardiovascular diseases such as coronary heart disease. Tanshinone IIA has been confirmed to suppress miR-1 and reduce the arrhythmogenesis after myocardial infarction (MI). However, the modulation mechanism is not clear. Tanshinone IIA was administrated daily for 7 days before ligation of the left anterior descending artery (LAD) and lasted for 3 months after LAD. Neonatal cardiomyocytes were exposed to 2% O(2)+95% N(2) condition for 24 h to simulate ischemia in vivo. Protein expression was examined with Western blot and miR-1 level was quantified by Real-time PCR. Our results showed that tanshinone IIA relieved ischemia-induced injury by improving the cardiac function. This beneficial effect may due to the depression of the elevated miR-1 level in ischemic and hypoxic cardiomyocytes, which subsequently restored its target Cx43 protein. Furthermore, tanshinone IIA could inhibit activated p38 MAPK and heart special transcription factors SRF and MEF2, in ischemic and hypoxic cardiomyocytes. Pretreatment with p38 MAPK inhibitor, SB203580 (10 uM), significantly relieved hypoxia-induced miR-1 increment and restored its downstream target Cx43 protein expression. These data suggest that tanshinone IIA play a role in protection cardiomyocytes from ischemic and hypoxic injury. The effect is based on inhibiting miR-1 expression through p38 MAPK signal pathway. This might provide us a new target to explore the novel strategy for ischemic cardioprotection.
AuthorsYong Zhang, Li Zhang, Wenfeng Chu, Bing Wang, Jialin Zhang, Mei Zhao, Xuelian Li, Baoxin Li, Yanjie Lu, Baofeng Yang, Hongli Shan
JournalCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 26 Issue 6 Pg. 991-8 ( 2010) ISSN: 1421-9778 [Electronic] Switzerland
PMID21220930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 S. Karger AG, Basel.
Chemical References
  • Connexin 43
  • Diterpenes, Abietane
  • Imidazoles
  • MicroRNAs
  • Pyridines
  • SB 203580
  • SRF protein, human
  • Serum Response Factor
  • tanshinone
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Connexin 43 (metabolism)
  • Diterpenes, Abietane (chemistry, pharmacology)
  • Imidazoles (pharmacology)
  • MicroRNAs (metabolism)
  • Myocardial Infarction (metabolism)
  • Myocytes, Cardiac (drug effects, enzymology, metabolism)
  • Phosphorylation
  • Pyridines (pharmacology)
  • Rats
  • Rats, Wistar
  • Serum Response Factor (metabolism)
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)

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