title: 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.
authors.affiliation: Department of Pharmacology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Chu
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Jialin
authors.initials: J
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Xuelian
authors.initials: X
authors.lastname: Li
authors.forename: Baoxin
authors.initials: B
authors.lastname: Li
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D035683:MicroRNAs / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D045784:Abietanes; D018031:Connexin 43; D007093:Imidazoles; D035683:MicroRNAs; D011725:Pyridines; C476858:SRF protein, human; D026362:Serum Response Factor; C021751:tanshinone; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580