Laboratório Integrado de Bioquímica Hatisaburo Masuda, NUPEM, Núcleo em Ecologia e Desenvolvimento Ambiental de Macaé, Universidade Federal do Rio de Janeiro, Avenida São José Barreto, N° 764, Bairro: São José do Barreto, Macaé, RJ CEP: 27.965-045, Brazil.
Laboratório Integrado de Computação Científica-LICC-NUPEM, Núcleo em Ecologia e Desenvolvimento Ambiental de Macaé, Universidade Federal do Rio de Janeiro, Avenida São José Barreto, N° 764, Bairro: São José do Barreto, Macaé, RJ CEP: 27.965-045, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2019 Aug;222:74-81. doi: 10.1016/j.cbpc.2019.04.007. Epub 2019 Apr 11.
Roundup® is currently the most widely used and sold agricultural pesticide in the world. The objective of this work was to investigate the effects of Roundup® on energy metabolism during zebrafish (Danio rerio) embryogenesis. The embryo toxicity test was performed for 96 h post-fertilisation and the sublethal concentration of Roundup® was defined as 58.3 mg/L, which resulted in failure to inflate the swim bladder. Biochemical assays were performed with viable embryos following glyphosate exposure, and no significant effects on protein, glucose, glycogen, triglyceride levels or the enzymatic activities of alanine aminotransferase and aspartate aminotransferase were observed. However, the activity of hexokinase was significantly altered following exposure to 11.7 mg/L Roundup®. Through molecular docking we have shown for the first time that the interactions of glucokinase and hexokinases 1 and 2 with glyphosate showed significant interactions in the active sites, corroborating the biochemical results of hexokinase activity in zebrafish exposed to the chemical. From the results of molecular docking interactions carried out on the Zfishglucok, ZfishHK1 and ZfishHK2 models with the glyphosate linker, it can be concluded that there are significant interactions between glyphosate and active sites of glucokinase and hexokinase 1 and 2 proteins. The present work suggests that Roundup® can induce problems in fish embryogenesis relating to the incapacity of swim bladder to inflate. This represents the first study demonstrating the interaction of glyphosate with hexokinase and its isoforms.
Roundup® 是目前世界上使用最广泛和销量最大的农业农药。本工作旨在研究 Roundup® 对斑马鱼胚胎发生过程中能量代谢的影响。胚胎毒性试验在受精后 96 小时进行,确定的亚致死浓度 Roundup® 为 58.3mg/L,导致鳔无法充气。在暴露于草甘膦后,对具有活力的胚胎进行生化分析,未观察到对蛋白质、葡萄糖、糖原、甘油三酯水平或丙氨酸氨基转移酶和天冬氨酸氨基转移酶的酶活性有显著影响。然而,暴露于 11.7mg/L Roundup® 后,己糖激酶的活性明显改变。通过分子对接,我们首次表明,葡萄糖激酶和己糖激酶 1 和 2 与草甘膦的相互作用在活性部位显示出显著的相互作用,这与暴露于该化学物质的斑马鱼中己糖激酶活性的生化结果相符。从对 Zfishglucok、ZfishHK1 和 ZfishHK2 模型与草甘膦连接子进行的分子对接相互作用的结果可以得出结论,草甘膦与葡萄糖激酶和己糖激酶 1 和 2 蛋白的活性部位之间存在显著的相互作用。本工作表明,Roundup® 可能会导致鱼类胚胎发生中出现与鳔无法充气有关的问题。这是首次证明草甘膦与己糖激酶及其同工酶相互作用的研究。