Contribution of Disruption in Creatine Synthesis and Transporter to 6-PPD Quinone Induced Immunosuppression in...

6-PPD quinone (6-PPDQ) has been recognized as a typical emergent contaminant with the potential to cause multiple aspects of damage to organisms. Creatine is an important metabolite that mediates energy homeostasis. In Caenorhabditis elegans, creatine content was reduced by 0.1-10 μg/L of 6-PPDQ, which was accompanied by a decrease in the expression of argk-1 encoding a creatine kinase and snf-5 encoding a potential creatine transporter. Creatine content could be reduced by RNAi of argk-1 and snf-5. Moreover, RNAi of argk-1 and snf-5 aggravated 6-PPDQ-induced immunosuppression, reflected by decreased expression of antimicrobial genes (lys-7 and spp-1), and double RNAi of argk-1 and snf-5 resulted in more severe immunosuppression induction in 6-PPDQ-exposed nematodes. After 6-PPDQ exposure, RNAi of argk-1 and snf-5 decreased the expression of aak-2 encoding AMPK, and aak-2 RNAi also strengthened 6-PPDQ-induced immunosuppression. During control of 6-PPDQ caused immunosuppression, ARGK-1, SNF-5, and AAK-2 modulated expressions of PMK-1/p38 MAPK and DAF-16 signals. The immunosuppression and inhibition in PMK-1 and DAF-16 expressions induced by 6-PPDQ could be further suppressed by creatine treatment. Therefore, the environmental exposure risk of 6-PPDQ in disrupting creatine synthesis and transporter was suggested, which potentially contributes to the induction of immunosuppression in nematodes.