1 / 2019-08-19 10:56:14

Molecular mechanisms for TF/MXL-3 in the regulation of Graphene Oxide toxicity in Caenorhabditis elegans

graphene oxide, MXL-3, LGG-1, Caenorhabditis elegans

Graphene oxide (GO) brings great application value to our society, meanwhile poses a great threat to human health. MXL-3 is a conserved transcription factor, which plays a vital role in regulating the physiological functions of Caenorhabditis elegans. However, the molecular mechanisms of MXL-3 against GO toxicity remained unclear. In this study, using in vivo assay system, we investigated the underlying molecular mechanism of MXL-3 in response to GO exposure. GO exposure suppressed the transcriptional expression of MXL-3 gene. Mroeover, neuron-specific RNAi knockdown of MXL-3 and intestine-specific RNAi knockdown of MXL-3 could induce a resistant property to GO toxicity. In the neurons, MXL-3 regulated the response to GO toxicity by activing MEK-2-MPK-1-SKN-1b signaling cascade. In the intestine, SKN-1c/HLH-30 acted downstream of MXL-3, and LGG-1, a homologue of human GABA type A receptor-associated protein, further acted downstream of the SKN-1c/HLH-30 to regulate the response to GO exposure.Therefore, a signaling cascade of MXL-3- SKN-1c/HLH-30-LGG-1 was identified to be involved in the regulation of response to GO toxicity. Our results demonstrate the crucial function of MXL-3 for animals in response to nanomaterial exposure.