Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase.

Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase.
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DOI:
10.1016/j.lfs.2008.08.003
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发表时间:
2008-10-10
期刊:
影响因子:
6.1
通讯作者:
LeBoeuf, Renee C.
LeBoeuf, Renee C.
中科院分区:
医学2区
文献类型:
--
作者:
Li, Yu-I;Elmer, Gary;LeBoeuf, Renee C.

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丹参酮Ⅱ A是丹参(Salvia miltiorrhiza)中的一种重要成分,在我国用于治疗动脉粥样硬化、心绞痛等心血管疾病已有数百年的历史。有许多报道称TIIA具有抗氧化特性,但化学结构表明TIIA被完全氧化。在这里,我们测试的假设,TIIA改变特定的抗氧化酶的表达和/或活性,以保护细胞免受氧化损伤。我们利用J774巨噬细胞来模拟用H2 O2攻击时对TIIA的细胞应答。研究了几种抗氧化酶的表达和活性水平,TIIA调节的唯一系统是谷胱甘肽过氧化物酶(GPx)。GPx-1 mRNA水平显着增加TIIA,但不是维生素E类似物,Trolox。GPx活性也显着增加TIIA。巯基琥珀酸抑制GPx活性,TIIA的保护作用减弱。因此,TIIA保护培养的巨噬细胞免受H2 O2诱导的细胞死亡,并且保护在很大程度上是通过TIIA诱导GPx基因表达和活性介导的。由于GPx在健康中的重要性,因为TIIA能够在一定程度上调节GPx的活性在细胞培养中,我们认为,TIIA是一个值得进一步研究的候选人在动脉粥样硬化的动物模型,并最终在人类的前瞻性试验。
Tanshinone IIA is an important ingredient in the herb danshen (Salvia miltiorrhiza), which has been used to treat cardiovascular diseases such as atherosclerosis and angina for hundreds of years in China. There are numerous reports that TIIA has antioxidant properties but the chemical structure indicates that TIIA is fully oxidized. Here, we test the hypothesis that TIIA alters the expression and/or activity of specific anti-oxidation enzymes to protect cells from oxidant damage. We utilized J774 macrophages to model cellular responses to TIIA when challenged with H2O2. Expression and activity levels of several anti-oxidation enzymes were investigated and the only system modulated by TIIA was glutathione peroxidase (GPx). GPx-1 mRNA levels were significantly increased by TIIA but not the vitamin E analogue, Trolox. GPx activities were also significantly increased by TIIA. Mercaptosuccinic acid inhibited GPx activity and the protective effect of TIIA was attenuated. Thus, TIIA protects cultured macrophages from H2O2-induced cell death and protection is mediated in large part by TIIA induction of GPx gene expression and activity. Because of the importance of GPx in health and because TIIA is able to modulate GPx activity to some extent in cell culture, we suggest that TIIA is a worthwhile candidate for further study in animal models of atherosclerosis and eventually in human prospective trials.
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