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首页> 外文期刊>Molecular and Cellular Biochemistry: An International Journal for Chemical Biology >The lipophilic vitamin C derivative, 6-o-palmitoylascorbate, protects human lymphocytes, preferentially over ascorbate, against X-ray-induced DNA damage, lipid peroxidation, and protein carbonylation
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The lipophilic vitamin C derivative, 6-o-palmitoylascorbate, protects human lymphocytes, preferentially over ascorbate, against X-ray-induced DNA damage, lipid peroxidation, and protein carbonylation

机译:亲脂性维生素C衍生物6-o-palmitoylascorbate保护人类淋巴细胞(优先于抗坏血酸)免受X射线诱导的DNA损伤,脂质过氧化和蛋白质羰基化

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摘要

The aim of this study was to investigate protective effects of the lipophilic vitamin C derivative, 6-o-palmitoylascorbate (PlmtVC), against X-ray radiation-induced damages including cell death, DNA double-strand breaks (DSBs), lipid peroxidation, and protein carbonylation in human lymphocytes HEV0082, and the stability of PlmtVC under cell-cultured or cell-free condition. Irradiation with X-ray (1.5 Gy) diminished the cell viability and induced apoptosis, both of which were protected by pre-irradiational administration with PlmtVC. Gamma-H2A.X foci as a hallmark of DSBs were markedly enhanced in the irradiated cells. PlmtVC prevented X-ray-induced DSBs more appreciably than l-ascorbic acid (l-AA). Intracellular ROS production, lipid peroxidation, and protein carbonylation in HEV0082 cells were increased by X-ray at 1.5 Gy, all of which were significantly repressed by PlmtVC. PlmtVC also elevated endogenous reduced glutathione (GSH) in HEV0082 cells, and prevented X-ray-induced GSH depletion that are more appreciably over l-AA. Thus, PlmtVC prevents X-ray-induced cell death through its antioxidative activity. Stability tests showed that after being kept under physiological conditions (pH 7.4, 37 A degrees C) for 14 days, vitamin C residual rates in PlmtVC solutions (62.2-82.0 %) were significantly higher than those in l-AA solutions (20.5-28.7 %). When PlmtVC or l-AA was added to HEV0082 lymphocytes, intracellular vitamin C in l-AA-treated cells was not detectable after 24 h, whereas PlmtVC-treated cells could keep a high level of intracellular vitamin C, suggesting an excellent stability of PlmtVC. Thus, X-ray-induced diverse harmful effects could be prevented by PlmtVC, which was suggested to ensue intrinsically from the persistent enrichment of intracellular vitamin C, resulting in relief to X-ray-caused oxidative stress.
机译:这项研究的目的是研究亲脂性维生素C衍生物6-邻-棕榈糖原酸酯(PlmtVC)对X射线辐射诱导的损伤的保护作用,包括细胞死亡,DNA双链断裂(DSB),脂质过氧化,细胞培养或无细胞条件下人淋巴细胞HEV0082的蛋白质和蛋白质羰基化以及PlmtVC的稳定性。用X射线(1.5 Gy)照射会降低细胞活力并诱导细胞凋亡,这两者都受到PlmtVC的预照射管理的保护。作为DSBs标志的Gamma-H2A.X焦点在受辐照的细胞中明显增强。与1-抗坏血酸(1-AA)相比,PlmtVC可以更有效地阻止X射线诱导的DSB。 X射线在1.5 Gy下增加HEV0082细胞的细胞内ROS产生,脂质过氧化和蛋白质羰基化,PlmtVC均显着抑制了这些细胞。 PlmtVC还提高了HEV0082细胞中的内源性还原型谷胱甘肽(GSH),并阻止了X射线诱导的GSH消耗,这种消耗比I-AA更明显。因此,PlmtVC通过其抗氧化活性防止X射线诱导的细胞死亡。稳定性测试表明,在生理条件下(pH 7.4,37 A摄氏度)放置14天后,PlmtVC溶液中的维生素C残留率(62.2-82.0%)显着高于l-AA溶液中的维生素C残留率(20.5-28.7) %)。当将PlmtVC或l-AA添加到HEV0082淋巴细胞中时,在24小时后无法检测到l-AA处理的细胞中的细胞内维生素C,而PlmtVC处理的细胞可以保持高水平的细胞内维生素C,这表明PlmtVC具有出色的稳定性。因此,PlmtVC可以防止X射线引起的各种有害影响,这被认为是由于细胞内维生素C的持续富集而固有地发生的,从而减轻了X射线引起的氧化应激。

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