Long-Term Exposure to 6-PPD Quinone Inhibits Glutamate Synthesis and Glutamate Receptor Function Associated with Its Toxicity Induction in .

6-PPD quinone (6-PPDQ) is widely distributed in environments. In , we first examined the effects of 6-PPDQ on glutamate synthesis and receptor function by analyzing glutamate content, related gene expression, and phenotypes after RNAi of these genes. Moreover, we performed glutamate treatment after 6-PPDQ exposure to determine the potential pharmacological effects of glutamate against 6-PPDQ toxicity. After exposure, the glutamate content was reduced by 0.1-10 μg/L 6-PPDQ, which was due to decreased expression of , , and governing glutamate synthesis from α-ketoglutarate, glutamine, and proline. RNAi of , , and decreased glutamate content in 6-PPDQ-exposed nematodes, and caused susceptibility to 6-PPDQ toxicity. Among glutamate transporter genes, expression was decreased by 0.1-10 μg/L 6-PPDQ. Moreover, 0.1-10 μg/L 6-PPDQ decreased glutamate receptor genes (, , and ), and their expression was decreased by RNAi of , , , and . RNAi of these receptor genes resulted in susceptibility to 6-PPDQ toxicity, and , , and were identified as targets of neuronal , , and . Furthermore, 5 mM glutamate suppressed 6-PPDQ toxicity and increased expression of , , and . Our results demonstrated the risk of 6-PPDQ exposure in disrupting glutamate synthesis and affecting function of glutamate receptors, which was related to 6-PPDQ toxicity induction.