Tanshinone IIA improves miR-133 expression through MAPK ERK1/2 pathway in hypoxic cardiac myocytes.
Tanshinone IIA is a lipid-soluble pharmacologically active compound extracted from the rhizome of Chinese herb Salvia miltiorrhiza, a well-known traditional Chinese medicine used for the treatment of cardiovascular disorders. Previous studies have identified that tanshinone IIA inhibited overexpression of miR-1 in hypoxic neonatal cardiomyocytes. This study was designed to examine the effects of tanshinone IIA on miR-133 expression under hypoxic condition. Neonatal rat cardiomyocytes were cultured in a hypoxic environment (2% O(2)+93% N(2)+5% CO(2)) at 37°C for 24 hours. MTT, TUNEL assays, and Flow Cytometry (FCM) were performed to identify cell apoptosis. Western blot was used to examine the expression of ERK1/2 and miR-133 level was quantified by Real-time PCR. Our results showed that apoptosis was induced by hypoxia. Typical apoptotic cells were seen by TUNEL assay, and FCM showed an apoptosis rate of 13.32% in hypoxic group. Apoptosis rate in hypoxic cells was reduced significantly by tanshinone IIA. In addition, the expression level of miR-133 was increased in hypoxic cells and further upregulated by tanshinone IIA. The stress-activated protein kinase MAPK ERK1/2 was activated by hypoxia and further increased with tanshinone IIA treatment. The present study demonstrated that tanshinone IIA enhanced cell resistance to hypoxic insult by upregulating miR-133 expression through activating MAPK ERK1/2 in neonatal cardiomyocytes.
Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Daqing, Heilongjiang, PR China.
Li
L
Zhang
Yanli
Y
Wu
Yumei
Y
Li
Chaoqian
C
Xu
Xuelian
X
Li
Daling
D
Zhu
Yan
Y
Zhang
Shu
S
Xing
Haoyan
H
Wang
Zhihua
Z
Zhang
Hongli
H
Shan
D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D035683:MicroRNAs / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D027561:Salvia miltiorrhiza / Q000737:chemistry
D045784:Abietanes; D004365:Drugs, Chinese Herbal; C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; C021751:tanshinone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3