Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells

Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells
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DOI:
10.1007/s10495-014-1032-x
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发表时间:
2014-11-01
期刊:
影响因子:
7.2
通讯作者:
Kondo, Takashi
Kondo, Takashi
中科院分区:
生物学2区
文献类型:
--
作者:
Wu, Li-Hua;Li, Peng;Kondo, Takashi

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电离辐射(IR)会产生活性氧(ROS)。过量的ROS有可能损害包括DNA、蛋白质和脂质在内的细胞大分子,最终导致细胞死亡。在这项研究中,我们通过测量X-射线照射的U937细胞内羟基自由基的清除能力来评估熊果苷的潜力,熊果苷是一种从一系列传统草药中挑选出来的药物。熊果苷(氢醌-β-D-吡喃葡萄糖苷)是一种天然存在的对苯二酚葡萄糖苷,传统上被用来治疗色素障碍。然而,目前还没有关于熊果苷对IR诱导的细胞凋亡的影响的报道。我们证实熊果苷对X射线诱导的细胞凋亡具有保护作用。熊果苷与X射线联合应用可减少细胞内羟基自由基的产生,防止线粒体膜电位损失。还可下调全细胞裂解液中磷酸化JNK、磷酸化p38的表达,激活线粒体中的Bax。熊果苷还抑制细胞色素C从线粒体向胞浆的释放。为了验证JNK在X射线诱导的细胞凋亡中的作用,用JNK抑制剂对细胞进行预处理,发现JNK抑制剂可以减少X射线诱导的细胞凋亡。综上所述,我们的数据表明熊果苷通过减少细胞内羟基自由基的产生,抑制Bax-线粒体途径和激活JNK/p38MAPK途径而发挥抗细胞凋亡的作用。
Ionizing radiation (IR) can generate reactive oxygen species (ROS). Excessive ROS have the potential to damage cellular macromolecules including DNA, proteins, and lipids and eventually lead to cell death. In this study, we evaluated the potential of arbutin, a drug chosen from a series of traditional herbal medicine by measuring intracellular hydroxyl radical scavenging ability in X-irradiated U937 cells. Arbutin (hydroquinone-beta-D-glucopyranoside), a naturally occurring glucoside of hydroquinone, has been traditionally used to treat pigmentary disorders. However, there are no reports describing the effect of arbutin on IR-induced apoptosis. We confirmed that arbutin can protect cells from apoptosis induced by X-irradiation. The combination of arbutin and X-irradiation could reduce intracellular hydroxyl radical production and prevent mitochondrial membrane potential loss. It also could down-regulate the expression of phospho-JNK, phospho-p38 in whole cell lysate and activate Bax in mitochondria. Arbutin also inhibits cytochrome C release from mitochondria to cytosol. To verify the role of JNK in X-irradiation-induced apoptosis, the cells were pretreated with a JNK inhibitor, and found that JNK inhibitor could reduce apoptosis induced by X-irradiation. Taken together, our data indicate that arbutin plays an anti-apoptotic role via decreasing intracellular hydroxyl radical production, inhibition of Bax-mitochondria pathway and activation of the JNK/p38 MAPK pathway.