Abstract
Exposure to graphene oxide (GO) induced some dysregulated microRNAs (miRNAs), such as the increase in mir-247, in nematode Caenorhabditis elegans. We here further identified goa-1 encoding a Gαo and pkc-1 encoding a serine/threonine protein kinase as the targets of neuronal mir-247 in the regulation of GO toxicity. GO exposure increased the expressions of both GOA-1 and PKC-1. Mutation of goa-1 or pkc-1 induced a susceptibility to GO toxicity, and suppressed the resistance of mir-247 mutant to GO toxicity. GOA-1 and PKC-1 could also act in the neurons to regulate the GO toxicity, and neuronal overexpression of mir-247 could not affect the resistance of nematodes overexpressing neuronal goa-1 or pkc-1 lacking 3′-UTR to GO toxicity. In the neurons, GOA-1 acted upstream of diacylglycerol kinase/DGK-1 and PKC-1 to regulate the GO toxicity. Moreover, DGK-1 and GOA-1 functioned synergistically in the regulation of GO toxicity. Our results highlight the crucial role of neuronal Gαo signaling in response to GO in nematodes.
Highlights
Graphene oxide (GO), a member of graphenic nanomaterials, can be potentially applied in at least drug delivery, biosensors, bioimaging, cancer therapy, catalytic, and environmental decontamination due to its unique physical and chemical properties[12,13]
Among the searched genes possibly acting as the targets for mir-24718, goa-1, gpb-2, tcer-1, eat-16, rps-8, lin-41, cwn-1, vhp-1, rab-39, ceh-18, acy-1, daf-19, pkc-1, lrk-1, cnb-1, dve-1, acs-22, egl-15, kin-1, mdt-15, apr-1, and dkf-2 are associated with the regulation of stress response in nematodes[21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]
We first provide several lines of evidence to indicate the potential role of GOA-1 and PKC-1 as the targets for neuronal mir-247 in the regulation of graphene oxide (GO) toxicity
Summary
Graphene oxide (GO), a member of graphenic nanomaterials, can be potentially applied in at least drug delivery, biosensors, bioimaging, cancer therapy, catalytic, and environmental decontamination due to its unique physical and chemical properties[12,13]. Exposure to GO resulted in damage on the functions of both primary targeted organs (such as intestine) and secondary targeted organs (such as neurons and reproductive organs)[6]. Molecular mechanism for the role of neuronal mir-247 in the regulation of GO toxicity is still unclear. We here further employed C. elegans to investigate the underlying mechanism for the function of neuronal mir-247 in regulating GO toxicity. We here identified GOA-1, an ortholog of heterotrimeric G protein α subunit Gαo, as a downstream target for neuronal mir-247 in regulating GO toxicity. In the neurons, a signaling cascade of GOA-1-DGK-1/PKC-1 was raised to explain the underlying mechanism for induction of GO toxicity. Our study provides an important molecular basis for neuronal Gαo signaling in response to GO in organisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
