Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes

Zhang, Mei-qi; Tu, Jian‐Feng; Chen, Huan; Ye, Shen; Pang, Lei; Yang, Xianghong; Zheng, Youbin

doi:10.3892/mmr.2014.3063

Cited by 10 publications

(6 citation statements)

References 26 publications

(31 reference statements)

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“…These results suggest that JAK2/STAT3 activation is involved in multiple HG-stimulated injuries. Our results are supported by several recent reports [ 31 – 33 ]. Previous research has found that AG490 exerts anti-inflammatory effects [ 34 , 35 ].…”

Section: Discussionsupporting

confidence: 93%

Naringin attenuates high glucose-induced injuries and inflammation by modulating the leptin-JAK2/STAT3 pathway in H9c2 cardiac cells

Luo

Ke²,

Xiong

et al. 2019

Arch Med Sci

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Introduction: Our previous study showed that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting p38 mitogen-activated protein kinase (MAPK). Leptin induces hypertrophy in rat cardiomyocytes via p38/MAPK activation. The present study aimed to test the hypothesis that leptin-Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), which are responsible for leptin's functions, are involved in HG-induced injuries and cardioprotective effects of NRG in cardiomyocytes. Material and methods: H9c2 cells were exposed to HG for 24 h to establish a cardiomyocyte injury model. Cells were pretreated with NRG and other drugs before exposure to HG. Protein expression was measured by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Apoptotic cells were assessed by Hoechst 33258 staining assay. Intracellular reactive oxygen species levels were determined by dichlorofluorescein diacetate staining. Mitochondrial membrane potential was evaluated using JC-1. An enzyme-linked immunosorbent assay was performed to determine the inflammatory cytokines. Results: NRG significantly attenuated HG-induced increases in leptin and Ob-R expression. Pretreatment with either a leptin antagonist (LA) or NRG markedly ameliorated HG-induced elevation of phosphorylated (p)-JAK2 and p-STAT3, respectively. Pretreatment with NRG, LA, Ob-R antagonist, or AG490 clearly alleviated HG-induced injuries and inflammation. Conclusions: This study provides new evidence of the NRG protective effects of H9c2 cells against HG-induced injuries possibly via modulation of the leptin-JAK2/STAT3 pathway.

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Section: Discussionsupporting

confidence: 93%

Naringin attenuates high glucose-induced injuries and inflammation by modulating the leptin-JAK2/STAT3 pathway in H9c2 cardiac cells

Luo

Ke²,

Xiong

et al. 2019

Arch Med Sci

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“…Our study has also demonstrated that TIIA (3 M) reduced hypoxia induced late apoptosis in H9C2 cells, the effect linked to decreasing hypoxia inducible factor-1 (HIF-1 ) translocation, balancing in Bcl-2/Bax ratio, reducing cytochrome c release and caspase 3 activity [36]. A recent study also found that the protection by TIIA on hypoxic ischemia-induced injury could be enhanced by the JAK2/STAT3 inhibitors [87]. Additionally, the antiapoptosis effects of TIIA were associated with regulation of intracellular calcium, ATP, mitochondrial superoxide, and SOD levels but not intracellular H 2 O 2 [35].…”

Section: Effects Of Tanshinones On Ischemia Reperfusion Injuriessupporting

confidence: 64%

Molecular Mechanisms of Cardioprotective Actions of Tanshinones

Jin¹,

2016

Journal of Chemistry

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Tanshinones are lipophilic compounds derived fromSalvia miltiorrhiza(Danshen) that has been widely used to treat coronary heart diseases in China. The cardioprotective actions of tanshinones have been extensively studied in various models of myocardial infarction, cardiac ischemia reperfusion injury, cardiac hypertrophy, atherosclerosis, hypoxia, and cardiomyopathy. This review outlines the recent development in understanding the molecular mechanisms and signaling pathways involved in the cardioprotective actions of tanshinones, in particular on mitochondrial apoptosis, calcium, nitric oxide, ROS, TNF-α, PKC, PI3K/Akt, IKK/NF-κB, and TGF-β1/Smad mechanisms, which highlights the potential of these compounds as therapeutic agents for treating cardiovascular diseases.

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“…[30][31][32] Its protective mechanisms have been broadly investigated. Several reports reveal the inhibited effect of TSA on ERS.…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested TSA is a plentiful lipophilic abietane diterpene element which was separated from Danshen (Salvia miltiorrhiza), a Traditional Chinese Medicine usually utilized for therapy of cardiovascular diseases. [30][31][32] Its protective mechanisms have been broadly investigated. Several reports reveal the inhibited effect of TSA on ERS.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA ameliorates apoptosis of cardiomyocytes induced by endoplasmic reticulum stress

Feng

Chen

2016

Exp Biol Med (Maywood)

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The fat-soluble diterpenoids tanshinone IIA (TSA) is the major active element of Danshen, which has widespread cardioprotective effect. However, the mechanism of its beneficial effect on cardiomyocytes has not been fully investigated. Here, we aim to demonstrate that TSA ameliorates apoptosis of cardiomyocytes activated by endoplasmic reticulum stress (ERS). Primary cultures of neonatal rat cardiomyocytes are used, in which ERS-mediated apoptosis is induced by tunicamycin (Tm). Apoptosis of cardiomyocytes are detected by Hoechst staining and caspase 3 activity analysis. Protein expression of ERS markers are detected by Western blot, and level of miroRNA-133 (miR-133) is detected by real-time polymerase chain reaction. Tm treatment significantly triggers the apoptosis and ERS of cardiomyocytes. TSA dramatically ameliorates apoptosis and ERS of cardiomyocytes induced by Tm. Interestingly, level of miR-133 is reduced by Tm treatment, which is reversed by TSA. The cardioprotective effect of TSA on apoptosis and ERS of cardiomyocytes is blocked by anti-miR-133. These results suggest that TSA protects cardiomyocytes through ameliorated ERS-mediated apoptosis, which may be resulted from upregulation of miR-133.

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Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes

Cited by 10 publications

References 26 publications

Naringin attenuates high glucose-induced injuries and inflammation by modulating the leptin-JAK2/STAT3 pathway in H9c2 cardiac cells

Naringin attenuates high glucose-induced injuries and inflammation by modulating the leptin-JAK2/STAT3 pathway in H9c2 cardiac cells

Molecular Mechanisms of Cardioprotective Actions of Tanshinones

Tanshinone IIA ameliorates apoptosis of cardiomyocytes induced by endoplasmic reticulum stress

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