Exposure to 6-PPD quinone disrupts glucose metabolism associated with lifespan reduction by affecting insulin and AMPK signals in Caenorhabditis elegans.

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.