Neuronal ERK Signaling In Response To Graphene Oxide In Caenorhabditis Elegans

Graphene oxide(GO),as a new type of nanomaterials,have a wide range of applications in many fields.With the application of GO,its safety and environmental exposure also attract people's concern.Extracellular signal-regulated kinase(ERK)signaling pathway is one of the important mitogen-activated protein kinase(MAPKs)signaling pathways and its mechanism in the regulation of GO toxicity has not been elucidated.We explored in vivo assay system of Caenorhabditis elegans to investigate the function of ERK signaling pathway in response to GO exposure and the molecular mechanism underlying.We chose lifespan and intestinal reactive oxygen species(ROS)production as the toxicity assessment endpoints.GO exposure increased the expression of MEK-2/MEK and MPK-1/ERK in the ERK signaling pathway.Mutation of mek-2 or mpk-1 resulted in a susceptibility to GO toxicity.Both MEK-2 and MPK-1 acted in the neurons to regulate the response to GO exposure.Neuronal overexpression of MEK-2 or MPK-1 caused a resistance to GO toxicity.In the neurons,SKN-1b/Nrf acted downstream of the MPK-1,and AEX-3,a guanine exchange factor for GTPase,further acted downstream of the SKN-lb to regulate the response to GO exposure.Therefore,a signaling cascade of MEK-2-MPK-1-SKN-1b/-AEX-3 was identified in the neurons required for the regulation of response to GO exposure.Moreover,genetic interaction assay demonstrated that the neuronal ERK signaling pathway and the intestinal p38 MAPK signaling pathway functioned synergistically in the regulation of response to GO exposure.Our results highlight the crucial function of the neuronal ERK signaling in the regulation of response to nanomaterials in organisms.Our data provide the evidence for ERK signaling in the regulation of GO toxicity.Our results about the role of ERK signaling pathway provide useful molecular targets for future chemical design or pharmacological prevention of certain nanomaterials.