title: Aflatoxin B1 augments the synthesis of corticotropin releasing hormone in JEG-3 placental cells.
abstract: Aflatoxins pose a major threat to food safety. These toxins are classified as hepatocarcinogens; however, their effect on the other tissues is unclear. During pregnancy, the fetus and placental tissues are especially sensitive to toxin exposure. In the present study aflatoxin B1 was found to induce the mRNA expression of corticotrophin-releasing hormone (CRH) in placental cells. A corresponding increase in CRH peptide in the culture medium was also observed. Since signal transduction pathways have been described previously in the control of CRH transcription, the status of protein kinase Cs (PKCs) and mitogen-activated protein kinases (MAPKs) were determined by Western analysis. In the aflatoxin B1-treated cultures, PKC α/βII/δ and ERK-1/2 were activated. As the PKC inhibitor bisindolylmaleimide I and the ERK inhibitor PD98059 could revert the induced CRH expression, the pathways dictated by PKC and ERK were likely involved in the transcriptional regulation. Electrophoretic mobility shift assay showed that C/EBP could be the ultimate activated transcription factor. Taken together, this study demonstrated that aflatoxin B1 could increase the parturition-related placental hormone in vitro. These findings might have significant implications for public health.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, People's Republic of China; Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Tan
authors.initials: T
authors.lastname: Wenjuan
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong; Food and Nutritional Sciences 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.
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D016604:Aflatoxin B1; D002118:Calcium
keywords: Aflatoxin B1; CRH; Placental cells