6-PPD quinone inhibits ammonia excretion to cause multiple aspects of toxicity in Caenorhabditis elegans by activating dual oxidase complex-SKN-1 axis.
Abstract — Entities Highlighted
Gene/ProteinChemicalDiseasePhenotypeAnatomyDev. Stage
Maintenance of normal ammonia excretion is critical for the health of organisms. We here examined effect of 6-PPD quinone (6-PPDQ) at environmentally relevant concentrations (ERCs, 0.1-10 μg/L) on ammonia excretion and its association with toxicity induction in nematodes. Ammonia excretion content was reduced by 6-PPDQ. Additionally, expressions of rhr-1, rhr-2, cah-4, eat-6, nhx-3, and vha-8 were decreased by 6-PPDQ, and ammonia excretion content was inhibited by epidermal RNAi of these genes. Animals with RNAi of these genes governing ammonia excretion showed susceptibility to 6-PPDQ toxicity. After 6-PPDQ exposure, epidermal RNAi of rhr-1, rhr-2, cah-4, eat-6, nhx-3, and vha-8 increased expression of genes (bli-3, tsp-15, and doxa-1) encoding dual oxidase complex. Ammonia excretion content after 6-PPDQ exposure was increased by epidermal RNAi of bli-3, tsp-15, and doxa-1, and resistance to 6-PPDQ toxicity was caused by epidermal RNAi of bli-3, tsp-15, and doxa-1. After 6-PPDQ exposure, epidermal RNAi of bli-3, tsp-15, and doxa-1 further increased expression of skn-1 encoding Nrf. Ammonia excretion content in 6-PPDQ exposed nematodes was decreased by epidermal RNAi of skn-1, and epidermal RNAi of skn-1 induced susceptibility to 6-PPDQ toxicity. Moreover, epidermal RNAi of skn-1 inhibited resistance of bli-3(RNAi), tsp-15(RNAi), and doxa-1(RNAi) to 6-PPDQ toxicity. Therefore, 6-PPDQ at ERCs could cause inhibition in ammonia excretion, which was linked to toxicity induction by activating dual oxidase complex-SKN-1 axis.
Relation Network
Specialists Used
gene_gene: 19
All Extracted Relations (24)
| Entity 1 | Relation | Entity 2 | Confidence | Specialist | Direction |
|---|---|---|---|---|---|
| cah-4 | regulation | nhx-3 | 100% | gene_gene | supports |
| bli-3 | regulation | tsp-15 | 100% | gene_gene | supports |
| bli-3 | regulation | tsp-15 | 100% | gene_gene | supports |
| rhr-2 | regulation | nhx-3 | 100% | gene_gene | supports |
| tsp-15 | regulation | doxa-1 | 100% | gene_gene | supports |
| tsp-15 | regulation | tsp-15 | 100% | gene_gene | supports |
| rhr-1 | regulation | eat-6 | 100% | gene_gene | supports |
| cah-4 | regulation | eat-6 | 100% | gene_gene | supports |
| rhr-1 | binding | rhr-2 | 100% | gene_gene | supports |
| rhr-1 | binding | rhr-2 | 100% | gene_gene | supports |
| skn-1 | regulation | bli-3(RNAi) | 99% | gene_gene | supports |
| rhr-1 | regulation | tsp-15 | 98% | gene_gene | supports |
| tsp-15 | regulation | skn-1 | 96% | gene_gene | supports |
| bli-3 | regulation | skn-1 | 93% | gene_gene | supports |
| skn-1 | regulation | doxa-1(RNAi) | 92% | gene_gene | supports |
| nhx-3 | regulation | doxa-1 | 90% | gene_gene | supports |
| bli-3(RNAi) | regulation | tsp-15(RNAi) | 88% | gene_gene | supports |
| cah-4 | regulation | bli-3 | 85% | gene_gene | supports |
| bli-3 | regulation | bli-3 | 83% | gene_gene | supports |
| skn-1 | negatively regulates | bli-3(RNAi) | 59% | — | supports |
| skn-1 | positively regulates | skn-1 | 59% | — | supports |
| bli-3 | causes | tsp-15 | 59% | — | supports |
| rhr-1 | negatively regulates | rhr-2 | 59% | — | supports |
| SKN-1 | positively regulates | axis | 54% | — | supports |