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H2O2促进氯化钆诱导HepG2细胞凋亡

发表时间:2013-04-15  浏览量:1382  下载量:424
全部作者: 叶丽华,刘会雪,王夔,杨晓达
作者单位: 北京大学医学部药学院
摘 要: 研究H2O2对氯化钆(GdCl3)诱导HepG2细胞凋亡的影响。结果显示:H2O2能够显著促进Gd3+诱导细胞凋亡;用Western blotting检测凋亡相关蛋白,发现H2O2与Gd3+共同作用时,可导致明显的DNA修复酶(poly ADP-ribose polymerase, PARP)剪切,但对凋亡相关促分裂素原活化蛋白激酶(mitogen-activated protein kinases, MAPK)以及线粒体信号通路的激活较两者单独作用都弱;溶液中H2O2和Gd3+共同作用可导致小牛胸腺DNA的断裂损伤。因此,上述结果表明H2O2促进Gd3+杀伤HepG2肿瘤细胞的机制不是通过增强Gd3+启动的细胞信号实现,而可能是二者共同作用造成对DNA的损伤所致,这为抗肿瘤稀土化合物研究提供了新的思路,有关其化学和分子生物学机制值得深入研究。
关 键 词: 生物无机化学;GdCl3;H2O2;细胞凋亡;癌症;HepG2
Title: Hydrogen peroxide promotes gadolinium-induced apoptosis of HepG2 cells
Author: YE Lihua, LIU Huixue, WANG Kui, YANG Xiaoda
Organization: School of Pharmaceutical Sciences, Peking University Health Science Center
Abstract: The present work investigated the roles of H2O2 on gadolinium (GdCl3)-induced apoptosis of HepG2 cancer cell line. The experimental results revealed that H2O2 promoted gadolinium-induced HepG2 apoptosis significantly. Analysis of apoptotic relevant proteins with Western blotting indicated that incubation of cells with (Gd3+) and H2O2 resulted in significant cleavage of poly ADP-ribose polymerase (PARP) proteins, but caused much weaker effects on mitogen-activated protein kinases (MAPK) or mitochondrial apoptotic signal transduction. Meanwhile, combination of (Gd3+) with hydrogen peroxide could cause fragmentations of calf thymus DNA. All these results suggested that, instead of enhancing Gd-induced cellular signal, H2O2 promoted HepG2 apoptosis by increasing Gd-induced DNA damages. Therefore, this mechanism might provide a new insight for design and discovery of anticaner lanthanide compounds, further works on the chemistry and molecular biology mechanisms would be appropriate.
Key words: bio-inorganic chemistry; GdCl3; H2O2; apoptosis; cancer; HepG2
发表期数: 2013年4月第7期
引用格式: 叶丽华,刘会雪,王夔,等. H2O2促进氯化钆诱导HepG2细胞凋亡[J]. 中国科技论文在线精品论文,2013,6(7):645-650.
 
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