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    题名: Aflatoxin B1 interferes with embryonic liver development: Involvement of p53 signaling and apoptosis in zebrafish
    作者: Cheng, YC;Wu, TS;Huang, YT;Chang, Y;Yang, JJ;Yu, FY;Liu, BH
    关键词: Aflatoxin B1;Liver development;p53 signaling;Apoptosis;Zebrafish embryos
    日期: 2021
    上传时间: 2022-08-05T09:45:33Z (UTC)
    出版者: ELSEVIER IRELAND LTD
    ISSN: 0300-483X
    摘要: Aflatoxin B-1 (AFB(1)), a naturally occurring mycotoxin, is present in human placenta and cord blood. AFB(1) at concentrations found in contaminated food commodities (0.25 and 0.5 mu M) did not alter the spontaneous movement, heart rate, hatchability, or morphology of embryonic zebrafish. However, around 86 % of 0.25 mu M AFB(1)-treated embryos had livers of reduced size, and AFB(1) disrupted the hepatocyte structures, according to histological analysis. Additionally, AFB(1) treatment that begins at any stage before 72 h post-fertilization (hpf) effectively reduced the size of embryonic livers. In hepatic areas, AFB(1) suppressed the expression of Hhex and Prox1, which are two critical transcriptional factors for initiating hepatoblast specification. KEGG analysis based on transcriptome profiling indicated that p53 signaling and apoptosis are the only observed pathways in AFB(1)-treated embryos. AFB(1) at 0.5 mu M significantly activated the expression of tp53, mdm2, puma, noxa, pidd1, and gadd45aa genes that are related to the p53 pathway and also that of baxa, casp 8 and casp 3a in the apoptotic process. TUNEL staining demonstrated that AFB(1) triggered the apoptosis of embryonic hepatocytes in a dose-dependent manner. These results indicate that the deficiency of both hhex and prox1 as well as hepatocyte apoptosis via the p53-Puma/Noxa-Bax axis may contribute to the embryonic liver shrinkage that is caused by AFB(1).
    URI: http://dx.doi.org/10.1016/j.tox.2021.152844
    https://www.webofscience.com/wos/woscc/full-record/WOS:000674669100015
    https://ir.csmu.edu.tw:8080/handle/310902500/23956
    關聯: TOXICOLOGY ,2021,v458
    显示于类别:[中山醫學大學研究成果] 期刊論文

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