title: Apoptosis signal-regulating kinase 1 promotes Ochratoxin A-induced renal cytotoxicity.
abstract: 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.
authors: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
authors: Rui
authors: R
authors: Liang
authors: 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.
authors: Xiao Li
authors: XL
authors: Shen
authors: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
authors: Boyang
authors: B
authors: Zhang
authors: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
authors: Yuzhe
authors: Y
authors: Li
authors: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
authors: Wentao
authors: W
authors: Xu
authors: Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA.
authors: Changhui
authors: C
authors: Zhao
authors: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
authors: YunBo
authors: Y
authors: Luo
authors: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P.R. China.
authors: Kunlun
authors: K
authors: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009793:Ochratoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D020543:Proteome / Q000032:analysis / Q000187:drug effects; D034622:RNA Interference; D012326:RNA Splicing / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D009793:Ochratoxins; D020543:Proteome; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C025589:ochratoxin A; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human
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