Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation.
Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation.
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Labdane 二萜可防止心肌细胞缺氧/再灌注损伤：参与 AKT 激活。
DOI：
10.1038/cddis.2011.113
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发表时间：
2011-11-10
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
几个labeloblastine二萜发挥抗炎和细胞保护作用，因此，我们已经研究了这些分子是否保护心肌细胞在缺氧/再灌注（A/R）模型，建立参与该过程的分子机制。本文研究了三种二萜类化合物（T1、T2和T3）对H9 c2细胞和离体大鼠心肌细胞A/R损伤的保护作用。在这两种情况下，治疗与二萜类T1和T2保护A/R诱导的细胞凋亡，推断的凋亡和caspase-3活性阳性细胞的百分比减少，Bcl-2/Bax的比例下降和抗凋亡蛋白的表达增加。细胞存活信号通路的分析表明，在A/R后加入的二萜T1和T2增加了磷酸化AKT和磷酸化ERK 1/2水平。当AKT活性受到抑制时，这些心脏保护作用丧失。此外，劳丹诱导的心脏保护涉及AMPK的激活，表明能量稳态在其作用机制中的作用。Labelditerpenes（T1和T2）也对A/R诱导的心肌细胞损伤具有心脏保护作用，其机制涉及激活特定的存活信号（PI 3 K/AKT通路，ERK 1/2和AMPK）和抑制凋亡。
Several labdane diterpenes exert anti-inflammatory and cytoprotective actions; therefore, we have investigated whether these molecules protect cardiomyocytes in an anoxia/reperfusion (A/R) model, establishing the molecular mechanisms involved in the process. The cardioprotective activity of three diterpenes (T1, T2 and T3) was studied in the H9c2 cell line and in isolated rat cardiomyocyte subjected to A/R injury. In both cases, treatment with diterpenes T1 and T2 protected from A/R-induced apoptosis, as deduced by a decrease in the percentage of apoptotic and caspase-3 active positive cells, a decrease in the Bcl-2/Bax ratio and an increase in the expression of antiapoptotic proteins. Analysis of cell survival signaling pathways showed that diterpenes T1 and T2 added after A/R increased phospho-AKT and phospho-ERK 1/2 levels. These cardioprotective effects were lost when AKT activity was pharmacologically inhibited. Moreover, the labdane-induced cardioprotection involves activation of AMPK, suggesting a role for energy homeostasis in their mechanism of action. Labdane diterpenes (T1 and T2) also exerted cardioprotective effects against A/R-induced injury in isolated cardiomyocytes and the mechanisms involved activation of specific survival signals (PI3K/AKT pathways, ERK1/2 and AMPK) and inhibition of apoptosis.
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