Tungsten carbide-cobalt particles activate Nrf2 and its downstream target genes in JB6 cells possibly by ROS generation.
Tungsten carbide-cobalt particles activate Nrf2 and its downstream target genes in JB6 cells possibly by ROS generation.
复制标题
DOI：
10.1615/jenvironpatholtoxicoloncol.v29.i1.60
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Xing-dong Zhang;Jinshun Zhao;L. Bowman;Xianglin Shi;V. Castranova;M. Ding
中科院分区：
文献类型：
--
作者：
Xing-dong Zhang;Jinshun Zhao;L. Bowman;Xianglin Shi;V. Castranova;M. Ding
由碳化钨（WC）和金属钴（Co）混合物组成的硬质金属在2003年被国际癌症研究机构评估为可能的人类致癌物。研究表明，核因子红系2相关因子2 （Nrf2）是化学敏感和转录系统之一，在化学毒性、致癌和病理过程中起重要作用。为了阐明WC-Co的健康危害机制，本研究在JB6细胞株上研究了纳米WC-Co颗粒对Nrf2信号通路的影响。纳米wc - co处理5小时后，Nrf2从细胞质中的Keap1中释放出来，并转运到细胞核中。Nrf2靶基因谷胱甘肽s转移酶（GST）和NAD(P)H：醌氧化还原酶1 （NQO1）活性在处理后24和48 H均升高。利用活性氧（ROS）敏感染料的研究表明，纳米wc - co颗粒处理的细胞中产生了活性氧。过氧化氢酶预处理细胞，而不是甲酸钠预处理细胞，对纳米wc - co颗粒诱导的Nrf2靶基因激活有显著的抑制作用。这些发现表明，Nrf2及其下游基因的激活可能是由ROS生成启动的，而ROS可能是纳米wc - co颗粒诱导的不良健康影响的主要因素。
Hard metal consisting of a mixture of tungsten carbide (WC) and metallic cobalt (Co) was evaluated as a possible carcinogen in humans by IARC in 2003. Studies have suggested that nuclear factor erythroid 2-related factor 2 (Nrf2) constitutes one of the chemical-sensing and transcription systems that play an essential role(s) in chemical toxicity, carcinogenesis, and pathological processes. To elucidate the mechanisms of health hazards of WC-Co, effects of nano-WC-Co particles on Nrf2 signaling pathway were investigated in the present study in a JB6 cell line. After a 5 h treatment with nano-WC-Co particles, Nrf2 was released from Keap1 in the cytoplasm and translocated into the nucleus. Enzymatic activities of Nrf2 target genes, including glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), increased at 24 and 48 h after the treatment. Studies using reactive oxygen species (ROS) sensitive dyes indicated that ROS were produced in nano-WC-Co particle-treated cells. Pretreatment of the cells with catalase, but not sodium formate, resulted in a significant inhibitory effect on nano-WC-Co particle-induced Nrf2 target gene activation. These findings suggest that activation of Nrf2 and its downstream genes may be initiated by ROS generation, and ROS may act as a major contributor in nano-WC-Co particle-induced adverse health effects.