Evaluation the role of insulin signaling pathway in reproductive toxicity of dispersed diesel particulate extract under environmental conditions

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Comparative Biochemistry and Physiology C-toxicology & Pharmacology Pub Date : 2024-06-10 DOI:10.1016/j.cbpc.2024.109959
Yajun Zhang , Xun Luo , Mengyun Zhu , Yu Wu
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Abstract

Diesel particulate extract (DPE), which is a significant constituent of airborne particle pollution, has a strong association with the development of cancer and respiratory diseases. Fulvic acid (FA), a plentiful organic macromolecule found in water, has the capability to modify particle surface charge and adsorption capacity when combined with minerals. Nevertheless, there is a scarcity of data regarding the influence of their interaction on DPE toxicity. To examine the impact of environmental factor on the toxic effects of DPE, we used the Caenorhabditis elegans (C. elegans) model to investigate the reproductive toxicity of DPE and FA on insulin signaling pathway. C. elegans were subjected to a semi-fluid medium (NGG) containing different concentrations of DPE or DPE + FA in order to assess germline apoptosis and the expression of important genes in the insulin signaling pathway. Through several mutant strains, we found that daf-2, age-1, pdk-1, akt-1 and daf-16 were involved in DPE-induced apoptosis. Furthermore, and the expression levels of these genes significantly altered. The ratio of daf-16 translocation to nucleation, as well as the amount of reactive oxygen species (ROS), exhibited a dose-response relationship, however, the presence of FA could altered these effects. The results revealed that the insulin signaling pathway plays a vital role in mediating the harmful effects caused by DPE, whereas environmental factors have a substantial impact on its toxicity. Moreover, it was noted that semi-fluid medium could effectively replicate three-dimensional exposure circumstances closely resembling those observed in actual situations.

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评估胰岛素信号通路在环境条件下分散柴油微粒萃取物生殖毒性中的作用
柴油微粒萃取物(DPE)是空气中微粒污染的重要成分,与癌症和呼吸系统疾病的发生密切相关。富维酸(FA)是一种大量存在于水中的有机大分子,当它与矿物质结合时,能够改变颗粒的表面电荷和吸附能力。然而,有关二者相互作用对 DPE 毒性影响的数据却很少。为了研究环境因素对 DPE 毒性作用的影响,我们使用 elegans(秀丽隐杆线虫)模型来研究 DPE 和 FA 对胰岛素信号通路的生殖毒性。将 elegans 放在含有不同浓度 DPE 或 DPE + FA 的半流体培养基(NGG)中,以评估生殖细胞凋亡和胰岛素信号通路中重要基因的表达。通过几个突变株,我们发现 daf-2、age-1、pdk-1、akt-1 和 daf-16 参与了 DPE 诱导的细胞凋亡。此外,这些基因的表达水平也发生了显著变化。daf-16 转位与成核的比例以及活性氧(ROS)的数量呈现出剂量反应关系,但 FA 的存在可能会改变这些效应。研究结果表明,胰岛素信号通路在介导 DPE 的有害效应中起着重要作用,而环境因素对其毒性有很大影响。此外,研究还注意到半流体培养基可以有效地复制与实际情况非常相似的三维暴露环境。
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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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