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首页> 外文期刊>The FEBS journal >Involvement of mitochondrial permeability transition pore opening in l-bisabolol induced apoptosis
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Involvement of mitochondrial permeability transition pore opening in l-bisabolol induced apoptosis

机译：线粒体通透性转变开孔参与l-bisabolol诱导的细胞凋亡

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l-Bisabolol is a natural monocyclic sesquiterpene alcohol. It has been used in cosmetics for hundreds of years because of its perceived skin-healing properties. l-Bisabolol is known to have anti-irritant, anti-inflammatory and antimicrobial properties. In precedent studies, we described how l-bisabolol exerts a selective pro-apoptotic action towards transformed cells [Cavalieri E et al. (2004) Biochem Biophys Res Commun315, 589-594] and its uptake is mediated by lipid rafts on the plasma membrane [Darra E et al. (2008) Arch Biochem Biophys476, 113-123]. In this study, we hypothesize that the intracellular target of l-bisabolol may be the mitochondrial permeability transition pore (mPTP). To evaluate this hypothesis, we used one transformed cell line (human glioma T67) in comparison with a nontransformed one (human fibroblasts). We assessed the effect of a specific mPTP inhibitor (cyclosporine A) on the toxic action of l-bisabolol. Results show that the l-bisabolol-induced decrease in oxygen consumption is abolished by the addition of cyclosporine A in T67 cells, indicating that l-bisabolol may target mPTP. The central role of mitochondria was also demonstrated by using galactose to force cells to a more aerobic metabolism. In this condition, we observed higher l-bisabolol toxicity. Furthermore, we studied the effect of l-bisabolol on isolated rat liver mitochondria. This study expands the notion of the specific action of l-bisabolol on transformed cells and suggests that it may act by disturbing the structure and function of the mPTP. l-Bisabolol toxicity is clearly related to its cellular uptake, which is higher in transformed cell lines.
机译：1-没药醇是天然的单环倍半萜烯醇。由于其可感知的皮肤愈合特性，它已在化妆品中使用了数百年。已知1-没食子醇具有抗刺激，抗炎和抗微生物的特性。在先例研究中，我们描述了1-bisabolol如何对转化细胞发挥选择性促凋亡作用[Cavalieri E等。 （2004）Biochem Biophys Res Commun315，589-594]，其摄取是由质膜上的脂筏介导的[Darra E et al。（2003）。 （2008）Arch Biochem Biophys 476，113-123]。在这项研究中，我们假设1-bisabolol的细胞内靶标可能是线粒体通透性转换孔（mPTP）。为了评估这一假设，我们使用了一种转化的细胞系（人神经胶质瘤T67）与未转化的细胞系（人成纤维细胞）进行比较。我们评估了特定的mPTP抑制剂（环孢素A）对1-bisabolol毒性作用的影响。结果表明，在T67细胞中加入环孢菌素A可以消除1-bisabolol诱导的耗氧量降低，这表明1-bisabolol可以靶向mPTP。线粒体的核心作用还通过使用半乳糖迫使细胞进行更富氧的代谢来证明。在这种情况下，我们观察到更高的l-bisabolol毒性。此外，我们研究了l-bisabolol对离体大鼠肝脏线粒体的影响。这项研究扩展了l-bisabolol对转化细胞的特定作用的概念，并暗示它可能通过干扰mPTP的结构和功能发挥作用。 1-没药醇的毒性明显与其细胞摄取有关，在转化的细胞系中更高。

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