PUBLICATION
Aflatoxin B1 interferes with embryonic liver development: involvement of p53 signaling and apoptosis in zebrafish
- Authors
- Cheng, Y.C., Wu, T.S., Huang, Y.T., Chang, Y., Yang, J.J., Yu, F.Y., Liu, B.H.
- ID
- ZDB-PUB-210703-46
- Date
- 2021
- Source
- Toxicology 458: 152844 (Journal)
- Registered Authors
- Keywords
- aflatoxin B1, apoptosis, liver development, p53 signaling, zebrafish embryos
- MeSH Terms
-
- Aflatoxin B1/toxicity*
- Animals
- Apoptosis/drug effects*
- Apoptosis Regulatory Proteins/drug effects
- Apoptosis Regulatory Proteins/genetics
- Dose-Response Relationship, Drug
- Embryonic Development/drug effects*
- Gene Expression Regulation, Developmental/drug effects
- Liver/drug effects*
- Liver/embryology*
- Liver/pathology
- MicroRNAs/biosynthesis
- MicroRNAs/genetics
- RNA, Messenger/biosynthesis
- RNA, Messenger/genetics
- Signal Transduction/drug effects*
- Teratogens/toxicity*
- Tumor Suppressor Protein p53/drug effects*
- Zebrafish/physiology*
- PubMed
- 34214637 Full text @ Toxicology
- CTD
- 34214637
Citation
Cheng, Y.C., Wu, T.S., Huang, Y.T., Chang, Y., Yang, J.J., Yu, F.Y., Liu, B.H. (2021) Aflatoxin B1 interferes with embryonic liver development: involvement of p53 signaling and apoptosis in zebrafish. Toxicology. 458:152844.
Abstract
Aflatoxin B1 (AFB1), a naturally occurring mycotoxin, is present in human placenta and cord blood. AFB1 at concentrations found in contaminated food commodities (0.25 and 0.5 μM) did not alter the spontaneous movement, heart rate, hatchability, or morphology of embryonic zebrafish. However, around 86% of 0.25 μM AFB1-treated embryos had livers of reduced size, and AFB1 disrupted the hepatocyte structures, according to histological analysis. Additionally, AFB1 treatment that begins at any stage before 72 hour post-fertilization (hpf) effectively reduced the size of embryonic livers. In hepatic areas, AFB1 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 AFB1-treated embryos. AFB1 at 0.5 μM 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 AFB1 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 AFB1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping