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© 2021 American Chemical Society.In this study, the association of expressional alterations in neuronal G protein–coupled receptors (GPCRs) with induction of protective response to polystyrene nanoparticles (PS–NPs) was investigated in Caenorhabditis elegans. On the basis of both phenotypic analysis and expression levels, the alterations in expressions of NPR–1, NPR–4, NPR–8, NPR–9, NPR–12, DCAR–1, GTR–1, DOP–2, SER–4, and DAF–37 in neuronal cells mediated the protective response to PS–NPs exposure. In neuronal cells, NPR–9, NPR–12, DCAR–1, and GTR–1 controlled the PS–NPs toxicity by activating or inhibiting JNK–1/JNK MAPK signaling. Neuronal NPR–8, NPR–9, DCAR–1, DOP–2, and DAF–37 controlled the PS–NPs toxicity by activating or inhibiting MPK–1/ERK MAPK signaling. Neuronal NPR–4, NPR–8, NPR–9, NPR–12, GTR–1, DOP–2, and DAF–37 controlled the PS–NPs toxicity by activating or inhibiting DBL–1/TGF–β signaling. Neuronal NPR–1, NPR–4, NPR–12, and GTR–1 controlled the PS–NPs toxicity by activating or inhibiting DAF–7/TGF–β signaling. Our data provides an important neuronal basis for induction of protective response to PS–NPs in C. elegans.
