Magnesium Lithospermate B Protects Cardiomyocytes from Ischemic Injury Via Inhibition of TAB1-p38 Apoptosis Signaling.
Magnesium Lithospermate B Protects Cardiomyocytes from Ischemic Injury Via Inhibition of TAB1-p38 Apoptosis Signaling.
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DOI：
10.3389/fphar.2010.00111
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发表时间：
2010
影响因子：
5.6
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Du CS;Yang RF;Song SW;Wang YP;Kang JH;Zhang R;Su DF;Xie X
丹参用于治疗心血管疾病已有数百年的历史。然而，其确切的心脏保护成分和潜在的机制仍不清楚。在本研究中，我们证明，在大鼠急性心肌梗死模型中，丹参酚酸的代表性成分紫草酸镁B（MLB）的治疗，显着减少梗死面积和血乳酸脱氢酶水平。而丹参中亲脂性丹参酮的代表成分丹参酮IIA则没有这种保护作用。此外，在模拟缺血细胞模型中，MLB处理显着增加了细胞活力并减少了亚G1群体和凋亡细胞核，表明其抗凋亡作用。进一步的机制研究表明，缺血诱导的p38磷酸化被MLB治疗取消。有趣的是，MLB通过破坏TGFβ活化蛋白激酶1结合蛋白1（TAB 1）与p38的相互作用，特异性地抑制TAB 1介导的p38磷酸化，但不影响丝裂原活化蛋白激酶3/6介导的p38磷酸化。结论：丹参中的MLB可能通过特异性抑制TAB 1-p38凋亡信号通路而保护心肌细胞免受缺血性损伤。这些结果表明TAB 1-p38相互作用作为治疗缺血性心脏病的假定药物靶标。
Danshen has been used in traditional Chinese medicine for hundreds of years to treat cardiovascular diseases. However, its precise cardioprotective components and the underlying mechanism are still unclear. In the present study, we demonstrated that in a rat model of acute myocardial infarction, the treatment with magnesium lithospermate B (MLB), the representative component of phenolic acids in Danshen, significantly reduced the infarct size and the blood lactate dehydrogenase level. In contrast, tanshinone IIA, the representative component of lipophilic tanshinones in Danshen, had no such protective effects. Moreover, in the simulated ischemia cell model, MLB treatment considerably increased the cell viability and reduced the sub-G1 population and the apoptotic nuclei, indicating its anti-apoptotic effect. Further mechanism study revealed that the ischemia-induced p38 phosphorylation was abolished by MLB treatment. Interestingly, MLB specifically inhibited the TGFβ-activated protein kinase 1-binding protein 1 (TAB1) mediated p38 phosphorylation through disrupting the interaction between TAB1 and p38, but it did not affect the mitogen-activated protein kinase 3/6 mediated p38 phosphorylation. In conclusion, the present study identifies MLB as an active component of Danshen in protecting cardiomyocytes from ischemic injury through specific inhibition of TAB1–p38 apoptosis signaling. These results indicate TAB1–p38 interaction as a putative drug target in treating ischemic heart diseases.
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