Wang Yiwen, Misto Maïlys, Yang Jing, Gehring Nicole, Yu Xiaoyu, Moussian Bernard
School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, China.
Interfaculty Institute for Cell Biology (Ifiz), University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.
Toxicol Rep. 2020 Dec 26;8:124-130. doi: 10.1016/j.toxrep.2020.12.014. eCollection 2021.
The thiol-containing compound Dithiothreitol (DTT) has been shown to be toxic to cultured cells by inducing the generation of reactive oxygen species that ultimately cause cell death. However, its effects on multicellular organisms and the environment have not been investigated yet in detail. In this work, we tested the toxicity of DTT to the model insect . We show that DTT is lethal to by topical application but not through feeding. DTT treatment triggers the transcription of the canonical apoptosis regulators , and at low amounts. The amplitude of this induction declines with elevating DTT amounts. By live microscopy, we observe apoptotic cells especially in the gut of DTT treated flies. In parallel, low DTT amounts also activate the expression of the cuticle barrier component gene . This indicates that a physical defence response is launched upon DTT contact. This combined measure is seemingly successful in preventing fly death. The expression of a number of known detoxification genes including , , and is also enhanced through DTT contact. The degree of upregulation of these genes is proportional to the applied DTT amounts. Despite this effort, flies exposed to high amounts of DTT eventually die. Together, is able to sense DTT toxicity and adjust the defence response successfully at least at low concentrations. This is the first time to analyse the molecular consequences of DTT exposure in a multicellular organism. Our work provides a new model to discuss the physiological response of animals against thiol toxins and to resurvey the effect of redox agents on the environment.
含硫醇化合物二硫苏糖醇(DTT)已被证明可通过诱导活性氧的产生对培养细胞产生毒性,最终导致细胞死亡。然而,其对多细胞生物和环境的影响尚未得到详细研究。在这项工作中,我们测试了DTT对模式昆虫的毒性。我们发现,通过局部应用DTT对[昆虫名称未给出]是致命的,但通过喂食则不然。低剂量的DTT处理会触发经典凋亡调节因子[凋亡调节因子名称未给出]、[凋亡调节因子名称未给出]和[凋亡调节因子名称未给出]的转录。随着DTT剂量的增加,这种诱导的幅度会下降。通过活体显微镜观察,我们尤其在经DTT处理的果蝇肠道中观察到凋亡细胞。同时,低剂量的DTT也会激活表皮屏障成分基因[基因名称未给出]的表达。这表明在接触DTT时会启动一种物理防御反应。这种联合措施似乎成功地防止了果蝇死亡。包括[解毒基因名称未给出]、[解毒基因名称未给出]、[解毒基因名称未给出]和[解毒基因名称未给出]在内的一些已知解毒基因的表达也通过接触DTT而增强。这些基因的上调程度与所应用的DTT剂量成正比。尽管如此,暴露于高剂量DTT的果蝇最终还是会死亡。总之,[昆虫名称未给出]能够感知DTT毒性,并至少在低浓度下成功调节防御反应。这是首次分析多细胞生物中DTT暴露的分子后果。我们的工作提供了一个新的模型,用于讨论动物对硫醇毒素的生理反应,并重新审视氧化还原剂对环境的影响。