Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio.
Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio.
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DOI：
10.1186/s12864-015-1941-2
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发表时间：
2015-10-24
期刊：
影响因子：
4.4
通讯作者：
Jackson DA
中科院分区：
文献类型：
--
作者：
Bui-Nguyen TM;Baer CE;Lewis JA;Yang D;Lein PJ;Jackson DA
已知接触有机磷农药敌敌畏（DDVP）会导致神经毒性以及其他代谢紊乱。然而，敌敌畏毒性的分子原因知之甚少，特别是在神经元和肌肉细胞以外的细胞中。为了更好地了解非神经元DDVP毒性的过程，我们将斑马鱼暴露于不同浓度的DDVP，并研究了肝脏组织学和基因转录的变化。对受敌敌畏暴露影响的基因的功能富集分析确定了肝脏中涉及能量利用和应激反应的一些过程。参与葡萄糖代谢的蛋白质的转录本的丰度受到了深刻的影响，这表明碳通量可能会转向戊糖磷酸途径，以补偿对能量的需求增加和解毒当量的减少。引人注目的是，参与β-氧化和脂肪酸合成的分子的许多转录物被下调。我们发现，参与活性氧反应以及泛素化、蛋白酶体降解和自噬的分子的信息水平增加。为了确保敌敌畏对能量代谢的影响不只是因为神经肌肉损伤的不良喂养的结果，我们禁食鱼29或50小时，并分析肝脏基因表达。在禁食和DDVP暴露的鱼的能量代谢的基因表达模式显着不同。我们观察到大量参与能量代谢和氧化应激反应的基因表达的协调变化。这些结果表明，敌敌畏的影响的一个可观的部分是对能量代谢和调节的信息水平。虽然我们观察到一些证据表明，暴露的鱼，可能会导致减少喂养的神经肌肉损伤，暴露的鱼的基因表达的改变不能很容易地解释营养剥夺。本文的在线版本（doi：10.1186/s12864-015-1941-2）包含补充材料，可供授权用户使用。
Exposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. However, the molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. To obtain a better understanding of the process of non-neuronal DDVP toxicity, we exposed zebrafish to different concentrations of DDVP, and investigated the resulting changes in liver histology and gene transcription. Functional enrichment analysis of genes affected by DDVP exposure identified a number of processes involved in energy utilization and stress response in the liver. The abundance of transcripts for proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to compensate for an elevated demand for energy and reducing equivalents for detoxification. Strikingly, many transcripts for molecules involved in β-oxidation and fatty acid synthesis were down-regulated. We found increases in message levels for molecules involved in reactive oxygen species responses as well as ubiquitination, proteasomal degradation, and autophagy. To ensure that the effects of DDVP on energy metabolism were not simply a consequence of poor feeding because of neuromuscular impairment, we fasted fish for 29 or 50 h and analyzed liver gene expression in them. The patterns of gene expression for energy metabolism in fasted and DDVP-exposed fish were markedly different. We observed coordinated changes in the expression of a large number of genes involved in energy metabolism and responses to oxidative stress. These results argue that an appreciable part of the effect of DDVP is on energy metabolism and is regulated at the message level. Although we observed some evidence of neuromuscular impairment in exposed fish that may have resulted in reduced feeding, the alterations in gene expression in exposed fish cannot readily be explained by nutrient deprivation. The online version of this article (doi:10.1186/s12864-015-1941-2) contains supplementary material, which is available to authorized users.