Tanshinone IIA Improves miR-133 Expression Through MAPK ERK1/2 Pathway in Hypoxic Cardiac Myocytes

Zhang, Li; Wu, Yanli; Li, Yumei; Xu, Chaoqian; Li, Xuelian; Zhu, Daling; Zhang, Yan; Xing, Shu; Wang, Haoyan; Zhang, Zhihua; Shan, Hongli

doi:10.1159/000341462

Cited by 38 publications

(32 citation statements)

References 35 publications

(43 reference statements)

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“…The relative expression of miR-133 was calculated and normalized to U6 using the comparative Cq method. Relative expression intensity values were calculated as 2 -ΔΔCq (16). The RT-qPCR was performed using the SYBR green method with an Applied Biosystems 7500 Real-Time PCR System (Thermo Fisher Scientific, Inc.).…”

Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

“…Due to their involvement in the regulation of gene expression, miRNAs serve an important role in cardiac function, including the conductance of electrical signals, heart muscle contraction, development and morphogenesis; miRNAs are also involved in the proliferation and apoptosis of cardiomyocytes, cardiac hypertrophy and heart failure (13)(14)(15). In particular, a number of studies suggest that miRNA-133 (miR-133) serves an important role in the cardiovascular system (15)(16)(17). In the present study, the role of miR-133 in the myocardial protective effect of tanshinone IIA against hydrogen peroxide (H 2 O 2 )-induced induce cell death was investigated.…”

Section: Introductionmentioning

confidence: 99%

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Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation

Liang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the cardioprotective effect of tanshinone IIA and the underlying molecular mechanisms. An in vitro model of oxidative stress injury was established in cardiac H9c2 cells, and the effects of tanshinone IIa were investigated using cell viability, reverse transcription-quantitative polymerase chain reaction and western blotting assays. The results demonstrated that tanshinone IIA protects H9c2 cells from H 2 O 2 -induced cell death in a concentration-dependent manner, via a mechanism involving microRNA-133 (miR-133), and that treatment with TIIA alone exerted no cytotoxic effects on H9c2. In order to further elucidate the mechanisms underlying the actions of TIIA, reverse transcription-quantitative polymease chain reaction and western blot analysis were performed. Reductions in miR-133 expression levels induced by increasing concentrations of H 2 O 2 were reversed by treatment with tanshinone IIA. In addition, the inhibition of miR-133 by transfection with an miR-133 inhibitor abolished the cardioprotective effects of tanshinone IIA against H 2 O 2 -induced cell death. Furthermore, western blot analysis demonstrated that tanshinone IIA activated Akt kinase via the phosphorylation of serine 473. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway by pretreatment with the PI3K specific inhibitors wortmannin and LY294002 also eliminated the cardioprotective effects of tanshinone IIA against H 2 O 2 -induced cell death. Western blot analysis demonstrated that H 2 O 2 -induced reductions in B cell lymphoma 2 (Bcl-2) expression levels were reversed by tanshinone IIA. In addition, the effect of tanshinone IIA on Bcl-2 protein expression level in an oxidative environment was suppressed by a PI3K inhibitor, wortmannin, indicating that tanshinone IIA exerts cardioprotective effects against H 2 O 2 -induced cell death via the activation of the PI3K/Akt signal transduction pathway and the consequent upregulation of Bcl-2. In conclusion, the present study demonstrates that TIIA is able to protcet H9c2 cells from oxidative stress-induced cell death through signalling pathways involving miR-133 and Akt, and that tanshinone IIA is a promising natural cardioprotective agent.

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Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation

Liang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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“…Growing evidences show that miRNAs play pivotal roles in diverse aspects of heart diseases, including myocardial ischemia [10,11], apoptosis [12,13], arrhythmia [14], cardiac fibrosis [15], and heart failure [16,17]. Notably, evidence from recent studies has shown that miRNAs are involved in regulating cardiomyocyte cell size, cardiac growth and fibrosis in cardiac hypertrophy [18,19].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-22 Downregulation by Atorvastatin in a Mouse Model of Cardiac Hypertrophy: a new Mechanism for Antihypertrophic Intervention

Wan

et al. 2013

Cell Physiol Biochem

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Background: Growing evidence shows that microRNAs (miRNAs) are involved in various cardiac processes including cardiac hypertrophy. However, the modulation of miRNA by pharmacological intervention in cardiomyocyte hypertrophy has not been disclosed yet. Methods: We constructed neonatal rat cardiomyocyte hypertrophy induced by angiotensin II stimulation and subjected to cardiomyocyte immunochemistry, qRT-PCR and immunoblotting analysis. In addition, we constructed the mouse cardiac hypertrophy using angomir-22 stimulation and demonstrated the potential antihypertrophic mechnism of atorvastatin. Results: The results showed that a collection of miRNAs were aberrantly expressed in hypertrophic cardiomyocytes induced by angiotensin II stimulation. In addition, overexpression of miR-22 was found in angiotensin II-induced hypertrophic cardiomyocytes, whereas administration of atorvastatin could reverse the upregulation of miRNA-22 nearly back to the control level. Furthermore, up-regulation of miRNA-22 in cardiomyocytes in vitro and in vivo could induce cardiac hypertrophy, which could suppress the protein level of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Concomitantly, the production of ANP, BNP and β-MHC was enhanced and cardiomyocyte size was increased. However, atorvastatin could markedly knockdown miRNA-22 expression and reverse these changes in cardiomyocytes. These results suggest that the contribution of atrovastatin to cardiomyocyte hypertrophy may be involved in downregulation of miRNA-22 expression, which modulates the activity of PTEN in cardiomyocyte hypertrophy. Conclusion: This study demonstrates for the first time the modulation of miRNA-22 can be achieved by pharmacological intervention. The data generated from this study provides a rationale for the development of miRNA-based strategies for antihypertrophic treatment.

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“…These results also suggest an anti-apoptotic function of miR-133. 25 Accordingly, the compound loss of both copies of miR-133a in mice (miR-133a-1 and miR-133a-2) resulted in enhanced apoptosis. 9,26 Finally, we observed a decreasing proliferation index with increasing gestational age, as measured by the expression of Ki67, where proliferation rates remained high until the 25 th gestational week, but decreased significantly after the 29 th gestational week.…”

Section: Discussionmentioning

confidence: 99%

miR-1, miR-133a/b, and miR-208a in human fetal hearts correlate to the apoptotic and proliferation markers

Boštjančič

Jerše

Glavač

et al. 2014

Exp Biol Med (Maywood)

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The heart is the first organ to function in the developing embryo. MicroRNAs (miRNAs) are small non-coding RNAs involved in the translational regulation of gene expression, which is beside transcriptional regulation crucial for the morphologic development of muscle tissue. The aim of our study was to test the hypothesis that the expression of miR-1, miR-133a/b, and miR-208a correlates with gestational age as well as with an apoptotic and proliferative index in the developing human heart. Our study included normal heart tissue samples obtained at autopsy from 46 fetuses, 12 children, and 15 adults. Proliferation and apoptosis were measured by the immunohistochemical detection of Ki67 and cleaved-CK18. Expression of miR-1, miR-133a, miR-133b, and miR-208a was measured using real-time PCR. We found a similar level of expression of miR-133a/b in fetal and children hearts that was different from the levels in healthy adults. We also found a correlation between a miR-208a expression to the gestational age of fetuses. We observed an inverse correlation between Ki67 expression and gestational age. Expression of Ki67 was positively correlated to the expression of miR-208a and miR-1, but inversely correlated to the expression of miR-133a/b. Expression of cleaved-CK18 was also inversely correlated to the expression of miR-133a/b. Our results showed a general decrease in the expression of miR-1 and an increase of miR-133a/b with increasing gestational age. We also found a general decrease in the expression of miR-208a, mimicking the expression of its host gene. Our results also suggest the involvement of miR-208a and miR-1 in the proliferation as well as anti-proliferative and anti-apoptotic roles of miR-133a/b.

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Tanshinone IIA Improves miR-133 Expression Through MAPK ERK1/2 Pathway in Hypoxic Cardiac Myocytes

Cited by 38 publications

References 35 publications

Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation

Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation

MicroRNA-22 Downregulation by Atorvastatin in a Mouse Model of Cardiac Hypertrophy: a new Mechanism for Antihypertrophic Intervention

miR-1, miR-133a/b, and miR-208a in human fetal hearts correlate to the apoptotic and proliferation markers

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