凋亡信号调节激酶1促进赭曲霉毒素A诱导的肾细胞毒性。
Apoptosis signal-regulating kinase 1 promotes Ochratoxin A-induced renal cytotoxicity.
作者信息
Liang Rui, Shen Xiao Li, Zhang Boyang, Li Yuzhe, Xu Wentao, Zhao Changhui, Luo YunBo, Huang Kunlun
机构信息
Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
1] Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China [2] School of Public Health, Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.
出版信息
Sci Rep. 2015 Jan 28;5:8078. doi: 10.1038/srep08078.
Oxidative stress and apoptosis are involved in Ochratoxin A (OTA)-induced renal cytotoxicity. Apoptosis signal-regulating kinase 1 (ASK1) is a Mitogen-Activated Protein Kinase Kinase Kinase (MAPKKK, MAP3K) family member that plays an important role in oxidative stress-induced cell apoptosis. In this study, we performed RNA interference of ASK1 in HEK293 cells and employed an iTRAQ-based quantitative proteomics approach to globally investigate the regulatory mechanism of ASK1 in OTA-induced renal cytotoxicity. Our results showed that ASK1 knockdown alleviated OTA-induced ROS generation and Δψm loss and thus desensitized the cells to OTA-induced apoptosis. We identified 33 and 24 differentially expressed proteins upon OTA treatment in scrambled and ASK1 knockdown cells, respectively. Pathway classification and analysis revealed that ASK1 participated in OTA-induced inhibition of mRNA splicing, nucleotide metabolism, the cell cycle, DNA repair, and the activation of lipid metabolism. We concluded that ASK1 plays an essential role in promoting OTA-induced renal cytotoxicity.
氧化应激和细胞凋亡参与了赭曲霉毒素A（OTA）诱导的肾细胞毒性。凋亡信号调节激酶1（ASK1）是丝裂原活化蛋白激酶激酶激酶（MAPKKK，MAP3K）家族成员，在氧化应激诱导的细胞凋亡中起重要作用。在本研究中，我们在HEK293细胞中对ASK1进行了RNA干扰，并采用基于iTRAQ的定量蛋白质组学方法全面研究ASK1在OTA诱导的肾细胞毒性中的调控机制。我们的结果表明，敲低ASK1可减轻OTA诱导的活性氧生成和线粒体膜电位丧失，从而使细胞对OTA诱导的凋亡不敏感。我们分别在乱序和ASK1敲低的细胞中鉴定出OTA处理后33种和24种差异表达蛋白。通路分类和分析显示，ASK1参与了OTA诱导的mRNA剪接抑制、核苷酸代谢、细胞周期、DNA修复以及脂质代谢的激活。我们得出结论，ASK1在促进OTA诱导的肾细胞毒性中起重要作用。
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