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过氧化氢和维生素 C 对鸡胚成纤维细胞的凋亡作用:氧化还原状态与细胞程序性死亡。

Apoptotic effects of hydrogen peroxide and vitamin C on chicken embryonic fibroblasts: redox state and programmed cell death.

机构信息

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, People's Republic of China.

出版信息

Cytotechnology. 2011 Oct;63(5):461-71. doi: 10.1007/s10616-011-9360-y. Epub 2011 Aug 6.

Abstract

The pro-apoptotic effects of hydrogen peroxide and the purported anti-apoptotic effects of Vitamin C on chicken embryonic fibroblasts were investigated. Hydrogen peroxide induced morphological changes in a dose dependent manner, and a myriad of autophagosomes were observed using transmission electron microscopy. Doxorubicin elicited alterations were not inhibited by co-incubation with Vitamin C except that mitochondrial structure was slightly improved. TUNEL assay, cytotoxicity analysis and flow cytometry revealed that the cytotoxicity, DNA fragmentation and apoptotic rates were dose dependent upon treatment with hydrogen peroxide. Calcium homeostasis was disrupted in a dose dependent manner, and cell cycle was blocked at G(2)/M checkpoint at low concentration and S/G(2) checkpoint at high concentration respectively upon treatment with hydrogen peroxide. The administration of Vitamin C only has a modest effect against doxorubicin induced apoptosis, calcium homeostasis disruption and cell cycle arrest. This research demonstrated that the elevation of reactive oxygen species is sufficient to induce the apoptosis of chicken embryonic fibroblasts, whereas the administration of Vitamin C does not necessarily have certain anti-apoptotic effects, especially when the stimulus is not directly linked with redox state.

摘要

研究了过氧化氢的促凋亡作用和维生素 C 据称的抗凋亡作用对鸡胚成纤维细胞的影响。过氧化氢以剂量依赖的方式诱导形态变化,并且使用透射电子显微镜观察到大量自噬体。阿霉素引起的改变不能被维生素 C 的共孵育所抑制,除了线粒体结构略有改善。TUNEL 测定、细胞毒性分析和流式细胞术显示,过氧化氢处理的细胞毒性、DNA 片段化和凋亡率均呈剂量依赖性。钙稳态以剂量依赖的方式受到破坏,并且过氧化氢处理分别在低浓度下阻断细胞周期在 G2/M 检查点,在高浓度下阻断 S/G2 检查点。维生素 C 的给药对阿霉素诱导的细胞凋亡、钙稳态破坏和细胞周期阻滞仅有适度的作用。这项研究表明,活性氧的升高足以诱导鸡胚成纤维细胞的凋亡,而维生素 C 的给药不一定具有确定的抗凋亡作用,特别是当刺激与氧化还原状态没有直接联系时。

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