The use of Drosophila melanogaster as a model organism to study immune-nanotoxicity

Abstract

Nanomaterials (NMs) are widely used in consumer and industrial products, as well as in the field of nanomedicine. Despite their wide array of applications, NMs are regarded as foreign entities by the body and thus induce various immune reactions. In mammals, NMs trigger differential recognition by immune cells such as macrophages, causing perturbation of the immune system. Studies on the pattern recognition of NMs have revealed that the Toll-like receptor signaling pathway plays an essential role in NM-induced innate immunity. However, effects caused by physicochemical properties of NMs on immune response and how NMs are recognized by immune cells are not fully understood. Furthermore, the complexity of the mammalian immune system and interspecies variation are still being debated, and the discordant results warrant the need to address these issues. Drosophila melanogaster has gained popularity as a model to study nanotoxicity. Drosophila innate immunity has extensively been studied, providing insights into our understanding of key signaling cascades involved, and importantly it has conserved immune-related genes and mechanogenetic pathways that represents a useful basis for studying its biological response at molecular level to environmental contaminants such as NMs. Moreover, various genetic tools and reagents enable to elucidate the molecular mechanisms underlying the internalization of NMs by immune cells. Furthermore, numerous forward and reverse genetic approaches can be employed to dissect complex biological processes, such as identifying signal transduction pathways and their core components involved in NM-induced immune responses. This review presents an overview of Drosophila innate immunity, as well as summarizes the impact of NM exposure on immune response in Drosophila. We also highlight the recent advancement of suitable methodologies and tools regarding the use of Drosophila as a model for studying the immune-related toxicity of NMs, taking into account the limitations associated with studying NM-induced toxicity in the mammalian system.     

Facilitating fructose-driven metabolism exerts a protective effect on anoxic stress in Drosophila

Hypoxic stress is linked to various cardiovascular disorders (e.g., stroke, myocardial infarction), mediated, at least in part, by a reduction in ATP synthesis. Fructose-driven glycolysis is proposed as an alternative pathway capable of sustaining ATP production even under anoxic conditions. Here, we tested the hypothesis that facilitating fructose-driven metabolism exerts a protective effect against anoxic stress in Drosophila. Genetically modified flies with the human fructose transporter (GluT5) and ketohexokinase (KHK) genes downstream of upstream activating sequence (UAS) were constructed. The GAL4-UAS system was confirmed to: (i) increase the expression of GluT5 and KHK in a tissue-specific and a time-dependent manner (i.e., whole flies [with Act5c-gene switch GAL4 driver], neurons [with elav-gene switch GAL4 driver]) and (ii) reduce mortality of flies when placed under anoxic stress. Taken together, these data suggest that increasing fructose metabolism may be a clinically relevant approach to minimize hypoxia-induced cellular damage.     

酸枣仁皂苷A对果蝇睡眠影响的量效关系与时效关系研究

目的 研究酸枣仁皂苷A对野生型CS品系果蝇睡眠作用影响的量效关系与时效关系.方法 选择野生型CS品系7d龄雄性果蝇为研究对象,采用液体给药的方式,利用果蝇活动监测系统,观察不同浓度酸枣仁皂苷A对果蝇睡眠影响的量效关系和时效关系.结果 1 mg/mL剂量为最佳给药浓度,给药3d为最佳给药时间,并可以明显延长果蝇白天平均睡眠的总时间和夜晚平均睡眠的总时间,增强果蝇的片段化睡眠.结论 酸枣仁皂苷A对野生型CS品系7d龄雄果蝇的睡眠具有一定的改善作用.     

阿尔茨海默病的发病机制和动物模型研究进展

阿尔茨海默病（Alzheimer's disease,AD）是一种慢性中枢神经系统退行性疾病。AD的病因不明、发病机制复杂,因此动物模型的建立对探索其发病机制及寻找防治疾病的药物具有重要作用。在动物模型中,转基因小鼠模型和转基因果蝇模型已成为研究热点。本文就阿尔茨海默病的发病机制和动物模型的研究现状进行综述。     

过表达DBHS家族基因可促进食管鳞癌细胞的迁移侵袭

目的 研究人类剪切蛋白(drosophila behavior human splicing,DBHS)家族基因,包括p5nrb、PSF、PSPC1基因,对食管鳞状细胞癌(以下简称食管磷癌)细胞系TE-8细胞系迁移、侵袭能力的影响。方法 构建p54nrb、PSF、PSPC1基因过表达载体,通过脂质体法转染TE-8细胞,转染48 h后qRT-PCR和Western blotting检测各组细胞p54nrb、PSF、PSPC1在mRNA和蛋白质水平的表达。细胞划痕实验及覆盖有Matrigel的Transwell小室检测食管鳞癌细胞的迁移、侵袭能力。结果 过表达p54nrb、PSF、PSPC1后,qRT-PCR和Western blotting检测证实食管鳞癌TE-8细胞中上述基因表达在mRNA水平和蛋白质水平均明显上调,细胞划痕实验及Transwell小室实验证实食管鳞癌TE-8细胞过表达p54nrb、PSF、PSPC1后,其迁移、侵袭能力增强。结论 过表达DBHS家族基因可促进食管鳞癌细胞的迁移侵袭。     

Is the white-ivory assay of Drosophila melanogaster a useful tool in genetic toxicology?

The white-ivory assay of Drosophila is based on the detection of reversions to wild-type phenotype of ommatidia with the white-ivory mutation. A tandem quadruplication of this gene is used in order to increase the reversion probability. Although the exact mechanism implicated in reversion is not known, revertant spots are believed to arise as a consequence of intrachromosomal recombination or related phenomena. Since the white-ivory assay has not been broadly used, the number of chemicals tested until now is still limited. In this work, we have assayed 25 chemicals belonging to several chemical groups, i.e., cross-linking agents, DNA-topoisomerase inhibitors, antimetabolites/nucleotide pool inhibitors, cyclic-adduct inducers, halogenated hydrocarbons, bulky-damage inducers, and a multiple damage inducer, to validate this test. Cross-linking agents, halogenated hydrocarbons, and the multiple damage inducer, daunomycin, were positive. On the contrary, the three antimetabolites/nucleotide pool inhibitors tested were negative. The other chemical groups showed disparate results, since some chemicals were positive, whereas others were negative in each group. A comparison with the results obtained in the w/w⁺ and mwh/flr³ assays shows that the wⁱ assay detects a more restricted spectrum of damages than those, although, with respect to carcinogenicity, its sensitivity (0.76, with the 62 chemicals tested until now) is similar to that estimated for the mentioned somatic assays. The conclusion of this work, then, is that the wⁱ assay is not recommended as a general screening test, because the background reversion frequencies show a high variability among solvents, the range of lesion-recognition is lower than in the w/w⁺ and mwh/flr³ SMARTs, and the mechanism implicated in the white-ivory reversion is poorly understood. Environ. Mol. Mutagen. 29:406–417, 1997 © 1997 Wiley-Liss, Inc.     

垂序商陆保肝作用及对果蝇寿命的影响

实验研究了垂序商陆的保肝作用及其对果蝇寿命的影响。结果发现垂序商陆水煎剂对 CCl4所致小鼠急性肝损伤有明显保护作用 ,其作用与给药剂量呈依赖关系 ;浓度为 2 5 μg/ml的垂序商陆总皂甙延长雄性果蝇的平均寿命(P<0 .0 5 )。