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ELUCIDATION OF ANTI-APOPTOTIC MECHANISMS OF TANSHINONE IIA REVEALS THE ROLE OF MIR-34 IN CARDIOMYOCYTE APOPTOSIS
CHU Xia 1,LU Huimin 1,BAI Yunlong 1,XIAO Jiening 2,PAN Zhenwei 1,LUO Xiaobin 2,ZHANG Yong 3,SHAN Hongli 1,LU Yanjie 1,YANG Baofeng 1,WANG Zhiguo 4 *
1.Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
2.Research Center, Montreal Heart Institute, Montreal, PQ H1T 1C8 Canada
3. Department of Medicine, University of Montreal, Montreal, PQ H3C 3J7, Canada
4. Research Center, Montreal Heart Institute, Montreal, PQ H1T 1C8 Canada
*Correspondence author
#Submitted by
Subject:
Funding: Specialized Research Fund for the Doctoral Program of Higher Education（No.SRFDP）
Opened online: 4 January 2011
Accepted by: none
Citation: CHU Xia,LU Huimin,BAI Yunlong.ELUCIDATION OF ANTI-APOPTOTIC MECHANISMS OF TANSHINONE IIA REVEALS THE ROLE OF MIR-34 IN CARDIOMYOCYTE APOPTOSIS[OL]. [ 4 January 2011] http://en.paper.edu.cn/en_releasepaper/content/4401790
 
 
In this paper，microRNAs (miRNAs) have recently emerged as a central player of gene regulatory network involved in decision of cell fate. Apoptosis, an active process that leads to cell death, has been shown to be controlled by miRNAs. It has also been implicated in a variety of human disease, such as heart disease, and established as a target process for disease therapy. Tanshinone IIA (TIIA), a monomer of phenanthrenequinones used to treat cardiovascular diseases, is known to insert cardioprotective effects in myocardial infarction by targeting apoptosis through enhancing Bcl-2 expression. To explore the potential link between miRNAs and the anti-apoptotic action of TIIA, we studied the possible involvement of miRNAs. We found that expression of all three members of the miR-34 family, miR-34a, miR-34b and miR-34c that have been known to mediate the apoptotic effect of p53, was robustly upregulated after exposure to either the DNA-damaging agent doxorubicin or pro-oxidant H2O2 for 24 hr. This upregulation caused significant apoptotic cell death, as determined by DNA fragmentation, and the effects were reversed by the antisense to these miRNAs. Pretreatment of cells with TIIA prior to incubation with doxorubicin or H2O2 prevented upregulation of miR-34 and reduced apoptosis. We then established BCL2L2, API5 and TCL1, in addition to BCL2, as the novel target genes for miR-34. We further unraveled that repression of these genes by miR-34 accounts for their proapoptotic effect in cardiomyocytes whereas upregulation of these genes by TIIA through downregulating miR-34 is likely the molecular mechanism for its beneficial effect against ischemic myocardial injuries.
Keywords:Pharmacology；TIIA; miRNA; apoptosis
 
 
 

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