Molecular insights into 4-nitrophenol-induced hepatotoxicity in zebrafish: Transcriptomic, histological and targeted gene expression analyses

被引:39
作者
Lam, Siew Hong [1 ,2 ]
Ung, Choong Yong [1 ,4 ]
Hlaing, Mya Myintzu [1 ]
Hu, Jing [1 ]
Li, Zhi-Hua [1 ]
Mathavan, Sinnakaruppan [3 ]
Gong, Zhiyuan [1 ,2 ]
机构
[1] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore
[2] NUS Environm Res Inst, Singapore 117411, Singapore
[3] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore
[4] Univ Malaya, Inst Biol Sci, Bioinformat Programme, Kuala Lumpur 50603, Malaysia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2013年 / 1830卷 / 10期
基金
新加坡国家研究基金会;
关键词
4-Nitrophenol; Zebrafish; Liver; Transcriptomic; Microarray; Toxicity; ORGANIC PRIORITY POLLUTANTS; NF-KAPPA-B; PROTEIN-SYNTHESIS; SPOTTED-MICROARRAY; SET ENRICHMENT; ACUTE TOXICITY; P-NITROPHENOL; TRANSFER-RNA; RAT-LIVER; APOPTOSIS;
D O I
10.1016/j.bbagen.2013.06.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: 4-Nitrophenol (4-NP) is a prioritized environmental pollutant and its toxicity has been investigated using zebrafish, advocated as an alternative toxicological model. However, molecular information of 4-NP induced hepatotoxicity is still limited. This study aimed to obtain molecular insights into 4-NP-induced hepatotoxicity using zebrafish as a model. Methods: Adult male zebrafish were exposed to 4-NP for 8, 24, 48 and 96 h. Livers were sampled for microarray experiment, qRT-PCR and various histological analyses. Results: Transcriptomic analysis revealed that genes associated with oxidative phosphorylation and electron transport chain were significantly up-regulated throughout early and late stages of 4-NP exposure due to oxidative phosphorylation uncoupling by 4-NP. This in turn induced oxidative stress damage and up-regulated pathways associated with tumor suppressors Rb and p53, cell cycle, DNA damage, proteasome degradation and apoptosis. Pathways associated with cell adhesion and morphology were deregulated. Carbohydrate and lipid metabolisms were down-regulated while methionine and aromatic amino acid metabolisms as well as NFKB pathway associated with chronic liver conditions were up-regulated. Up-regulation of NFKB, NFAT and interleukin pathways suggested hepatitis. Histological analyses with specific staining methods and qRT-PCR analysis of selected genes corroborated with the transcriptomic analysis suggesting 4-NP induced liver injury. Conclusion: Our findings allowed us to propose a plausible model and provide a broader understanding of the molecular events leading to 4-NP induced acute hepatotoxicity for future studies involving other nitrophenol derivatives. General significance: This is the first transcriptomic report on 4-NP induced hepatotoxicity. (c) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:4778 / 4789
页数:12
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