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Neuronal ERK MAPK signaling in response to low-dose nanopolystyrene exposure by suppressing insulin peptide expression in Caenorhabditis elegans

The Science of The Total Environment 2020 78 citations

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Researchers found that nanopolystyrene exposure activates ERK MAPK signaling in C. elegans neurons, which suppresses three insulin peptide genes (ins-4, ins-39, daf-28) and subsequently modulates intestinal insulin receptor and FOXO transcription factor activity, revealing a neuron-to-intestine signaling axis as a key protective mechanism against nanoplastic toxicity.

The responses of different organs are important for organisms against the toxicity of environmental toxicants. So far, the neuronal response to nanoplastic exposure and the underlying mechanisms are still largely unclear. Due to the sensitivity to environmental exposures, we here employed Caenorhabditis elegans as an animal model to examine the role of ERK MAPK signaling pathway in the neurons to regulate the response to nanopolystyrene (100 nm). Nanopolystyrene exposure in the range of μg/L could significantly increase expressions of genes (lin-45, mek-2, and mpk-1) encoding ERK MAPK signaling pathway. Nanopolystyrene at the predicted environmental concentration of 1 μg/L could only significantly increase the mpk-1 expression. Meanwhile, RNAi knockdown of any of these genes caused a susceptibility to nanopolystyrene toxicity. ERK/MPK-1 acted in the neurons to regulate the response to nanopolystyrene. Moreover, three genes (ins-4, ins-39, and daf-28) encoding insulin peptides were identified as the downstream targeted genes of neuronal mpk-1 in regulating the response to nanopolystyrene. In nanopolystyrene exposed nematodes, neuronal RNAi knockdown of ins-4, ins-39, or daf-28 decreased expression of intestinal daf-2 encoding insulin receptor and increased expression of intestinal daf-16 encoding FOXO transcriptional factor. Therefore, the neuronal ERK MAPK signaling responded to nanopolystyrene by modulating the insulin signaling-mediated communication between neurons and intestine in nematodes. Our findings are helpful for understanding the molecular basis of neuronal response to nanopolystyrene in organisms.

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