Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Chemosphere. 2024 Sep;363:142975. doi: 10.1016/j.chemosphere.2024.142975. Epub 2024 Jul 29.
Glucose metabolism plays an important role for formation of normal physiological state of organisms. However, association between altered glucose metabolism and toxicity of 6-PPD quinone (6-PPDQ) remains largely unknown. In 1-100 μg/L 6-PPDQ exposed Caenorhabditis elegans, we observed increased glucose content. After 6-PPDQ exposure (1-100 μg/L), expressions of F47B8.10 and fbp-1 governing gluconeogenesis were increased, and expressions of hxk-1, hxk-3, pfk-1.1, pyk-1, and pyk-2 governing glycolysis were decreased. Under 6-PPDQ exposure condition, glucose content could be changed by RNAi of F47B8.10, hxk-1, and hxk-3, key genes for gluconeogenesis and glycolysis. In 6-PPDQ exposed nematodes, RNAi of daf-16 and aak-2 elevated glucose content, increased expressions of F47B8.10 and/or fbp-1, and decreased expressions of hxk-1, hxk-3, and/or pfk-1.1. Additionally, lifespan and locomotion during aging were increased by RNAi of F47B8.10 and decreased by RNAi of hxk-1 and hxk-3 in 6-PPDQ exposed nematodes. Moreover, after 6-PPDQ exposure, RNAi of F47B8.10 decreased expressions of insulin peptide genes (ins-7 and daf-28) and insulin receptor gene daf-2 and increased expressions of daf-16 and aak-2. In 6-PPDQ exposed nematodes, RNAi of hxk-1 and hxk-3 further increased expressions of ins-7, daf-28, and daf-2 and decreased expressions of daf-16 and aak-2. Our results demonstrated important association between altered glucose metabolism and toxicity of 6-PPDQ in inducing lifespan reduction in organisms.
葡萄糖代谢对于生物体正常生理状态的形成起着重要作用。然而，改变的葡萄糖代谢与 6-PPD 醌（6-PPDQ）毒性之间的关联在很大程度上仍是未知的。在 1-100μg/L 6-PPDQ 暴露的秀丽隐杆线虫中，我们观察到葡萄糖含量增加。在 6-PPDQ 暴露（1-100μg/L）后，调控糖异生的 F47B8.10 和 fbp-1 的表达增加，而调控糖酵解的 hxk-1、 hxk-3、pfk-1.1、pyk-1 和 pyk-2 的表达减少。在 6-PPDQ 暴露条件下，通过 RNAi 干扰 F47B8.10、 hxk-1 和 hxk-3 这三个调控糖异生和糖酵解的关键基因，可改变葡萄糖含量。在 6-PPDQ 暴露的线虫中，daf-16 和 aak-2 的 RNAi 使葡萄糖含量升高，F47B8.10 和/或 fbp-1 的表达增加，而 hxk-1、 hxk-3 和/或 pfk-1.1 的表达减少。此外，F47B8.10 的 RNAi 增加了 6-PPDQ 暴露线虫的寿命和衰老期间的运动，而 hxk-1 和 hxk-3 的 RNAi 则减少了寿命和运动。此外，在 6-PPDQ 暴露后，F47B8.10 的 RNAi 降低了胰岛素肽基因（ins-7 和 daf-28）和胰岛素受体基因 daf-2 的表达，增加了 daf-16 和 aak-2 的表达。在 6-PPDQ 暴露的线虫中， hxk-1 和 hxk-3 的 RNAi 进一步增加了 ins-7、daf-28 和 daf-2 的表达，降低了 daf-16 和 aak-2 的表达。我们的结果表明，改变的葡萄糖代谢与 6-PPDQ 的毒性之间存在重要关联，这导致了生物体寿命的缩短。
