Different stress condition stimulates the expression level of insulin-like growth factor receptor II (IGF-IIR) in cardiomyoblasts that lead to apoptosis. Tanshinone IIA (TSN), a pharmacologically active component from Danshen, has been shown cardioprotective effects against cardiac apoptosis induced by several stress conditions. Therefore, this study was conducted to assess the cardioprotective effects of TSN IIA mediated through the estrogen receptor (ER) in order to inhibit the Leu27IGF-II-enhanced IGF-IIR-mediated cardiac apoptosis. The estrogenic activity of TSN IIA was examined after myocardial cells were pretreated with the ER antagonist, and inhibited the phospho-inositide-3 kinase (PI3K). Here, we found that TSN IIA significantly induced ER that phosphorylated Akt. Further, Akt activation considerably suppressed the Leu27IGF-II induced IGF-IIR expression level and the downstream effectors, including Gαq and calcineurin as well as mitochondrial dependent apoptosis proteins including Bad, cytochrome c, and active caspase-3 that result in cardiac apoptosis resistance. However, the western blot analysis, JC-1 staining, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay revealed that TSN IIA attenuated Leu27IGF-II-induced IGF-IIR mediated cardiac apoptosis was reversed by an ER antagonist such as ICI 182780, and PI3K inhibition. All these findings demonstrate that TSN IIA exerts estrogenic activity, which can activate PI3K-Akt pathway, and thereby inhibits Leu27IGFII induced IGF-IIR mediated cardiac apoptosis. Thus, TSN IIA can be considered as an effective therapeutic strategy against IGF-IIR signaling cascade to suppress cardiac apoptosis.

中文翻译：

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丹参酮 IIA 通过雌激素受体介导的 Akt 激活抑制 Leu27IGF-II 诱导的胰岛素样生长因子受体 II 信号传导和心肌细胞凋亡

不同的应激条件刺激心肌细胞中胰岛素样生长因子受体 II (IGF-IIR) 的表达水平，导致细胞凋亡。丹参酮 IIA (TSN) 是一种来自丹参的药理活性成分，已显示出对多种应激条件诱导的心脏凋亡的心脏保护作用。因此，本研究旨在评估通过雌激素受体 (ER) 介导的 TSN IIA 的心脏保护作用，以抑制 Leu27IGF-II 增强的 IGF-IIR 介导的心脏细胞凋亡。在用 ER 拮抗剂预处理心肌细胞并抑制磷酸肌醇 3 激酶 (PI3K) 后，检查了 TSN IIA 的雌激素活性。在这里，我们发现 TSN IIA 显着诱导磷酸化 Akt 的 ER。更远，c和导致心脏细胞凋亡抵抗的活性 caspase-3。然而，蛋白质印迹分析、JC-1 染色和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记分析表明，TSN IIA 减弱了 Leu27IGF-II 诱导的 IGF-IIR 介导的心脏细胞凋亡，被内质网拮抗剂如 ICI 182780 逆转，和 PI3K 抑制。所有这些发现表明 TSN IIA 发挥雌激素活性，可以激活 PI3K-Akt 通路，从而抑制 Leu27IGFII 诱导的 IGF-IIR 介导的心脏细胞凋亡。因此，TSN IIA 可以被认为是一种有效的治疗策略，可以对抗 IGF-IIR 信号级联以抑制心脏细胞凋亡。