Aflatoxin B1 disrupts transient receptor potential channel activity and increases COX-2 expression in JEG-3 placental cells.
Aflatoxins are fungal metabolites which pose a major threat to food safety. Although these mycotoxins are established hepatocarcinogens, their effect on the reproductive organ is unknown. Transient Receptor Potential Channels (TRPs) are ubiquitously expressed in human tissues, including the placenta. These channels are associated with various functions in the placenta. The fetus and the placenta are especially sensitive to xenobiotic assault; therefore, exposure to the aflatoxins during gestation might lead to the undesirable outcome. Previously we have shown that aflatoxin B1 administered in late gestation may increase cox-2 expression in mouse placentae. In the present study, we examined the effect of aflatoxin B1 on COX-2 by using the placental cell model JEG-3 and the respective signaling pathway. In our result, COX-2 expression was induced by the mycotoxin administration. The intracellular calcium levels were also increased in cells by aflatoxin B1 treatment as little as 1 nM. Immunoblot result showed that some TRP expressions were elevated. As inflated intracellular calcium might activate MAPKs, the underlying signaling pathway was investigated. With the help of TRP-specific inhibitors, the mycotoxin appeared to increase the expression of TRPC-3 and activate PKCβ and ERK. The significance of COX-2 in pregnancy has been well established. Exposure to this mycotoxin may perturb the physiological processes dictated by COX-2 in pregnancy.
Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Yun
Y
Zhu
Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Yan Qin
YQ
Tan
Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong; Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address: laikleung@cuhk.edu.hk.
Lai K
LK
Leung
D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D010920:Placenta / Q000201:enzymology* / Q000473:pathology*; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D050051:Transient Receptor Potential Channels; D016604:Aflatoxin B1; D051546:Cyclooxygenase 2; D002118:Calcium
Aflatoxin B1; Placental cells; TRP