title: p53 activation inhibits ochratoxin A-induced apoptosis in monkey and human kidney epithelial cells via suppression of JNK activation.
abstract: Ochratoxin A (OTA), one of the major food-borne mycotoxins, induces apoptosis in various types of cells. Induction of apoptosis is suggested to be one of the major cellular mechanisms behind OTA-induced diverse toxic effects. However, the molecular mechanisms involved, especially the role of p53 in OTA-induced apoptosis have not been clearly elucidated. In the present study, we find that p53 activation exerts pro-survival function to inhibit apoptosis induction in MARC-145, Vero monkey kidney cells and HEK293 human kidney cells in response to ochratoxin A treatment. We further demonstrate that the pro-survival activity of p53 is attributed to its ability to suppress JNK activation that mediates apoptotic signaling through down-regulation of Bcl-xL. To our knowledge, this is first report of pro-survival role of p53 in OTA-induced apoptosis in kidney epithelial cells. Our findings provide a novel insight into the mechanisms of OTA-induced apoptosis in kidney epithelial cells.
authors.affiliation: Division of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.forename: Shutao
authors.initials: S
authors.lastname: Yin
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Dong
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000096:biosynthesis*; D014709:Vero Cells
chemical_list: D009183:Mycotoxins; D009793:Ochratoxins; D016159:Tumor Suppressor Protein p53; C025589:ochratoxin A; D048670:MAP Kinase Kinase 4