title: Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes.
abstract: Lipid rafts are microdomains in plasma membrane and can mediate cytotoxicity. In this study, the role of lipid rafts in ochratoxin A-induced toxicity was investigated using Hepatoblastoma Cell Line HepG-2 cells. Disruption of cholesterol-containing lipid rafts enhanced Ochratoxin A (OTA) toxicity, as shown by increased lactate dehydrogenase leakage, increased reactive oxygen species level and reduction of superoxide dismutase activity in a time-dependent manner. Isobaric tags for relative and absolute quantitation-based proteomics of the cell membranes showed that nearly 85.5% proteins were downregulated by OTA, indicating that OTA inhibited the membrane protein synthesis. Most of altered proteins were involved in Gene Ontology "transport", "cell adhesion" and "vesicle-mediated transport". In conclusion, lipid rafts play a key role in OTA-induced cytotoxicity. This study provides insight into how OTA toxicity is regulated by the plasma membrane, especially the lipid rafts.
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China. xuwentao@cau.edu.cn.|Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University (BTBU), Beijing, 100048, P.R. China. xuwentao@cau.edu.cn.
authors: Yu
authors: Y
authors: Zhang
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Xiaozhe
authors: X
authors: Qi
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Juanjuan
authors: J
authors: Zheng
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Yunbo
authors: Y
authors: Luo
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, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Junran
authors: J
authors: Hao
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Xiaohong
authors: X
authors: Li
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Kunlun
authors: K
authors: Huang
authors: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China 6 Agricultural University, Beijing, 100083, China.
authors: Wentao
authors: W
authors: Xu
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D009793:Ochratoxins / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D009793:Ochratoxins; D017382:Reactive Oxygen Species; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C025589:ochratoxin A; D002784:Cholesterol; D013482:Superoxide Dismutase
keywords: Hepatotoxicity; Lipid rafts; Membrane proteomics; Ochratoxin A; Plasma membrane