Abstract
BackgroundIntestinal barrier is crucial for animals against translocation of engineered nanomaterials (ENMs) into secondary targeted organs. However, the molecular mechanisms for the role of intestinal barrier against ENMs toxicity are still largely unclear. The intestine of Caenorhabditis elegans is a powerful in vivo experimental system for the study on intestinal function. In this study, we investigated the molecular basis for intestinal barrier against toxicity and translocation of graphene oxide (GO) using C. elegans as a model animal.ResultsBased on the genetic screen of genes required for the control of intestinal development at different aspects using intestine-specific RNA interference (RNAi) technique, we identified four genes (erm-1, pkc-3, hmp-2 and act-5) required for the function of intestinal barrier against GO toxicity. Under normal conditions, mutation of any of these genes altered the intestinal permeability. With the focus on PKC-3, an atypical protein kinase C, we identified an intestinal signaling cascade of PKC-3-SEC-8-WTS-1, which implies that PKC-3 might regulate intestinal permeability and GO toxicity by affecting the function of SEC-8-mediated exocyst complex and the role of WTS-1 in maintaining integrity of apical intestinal membrane. ISP-1 and SOD-3, two proteins required for the control of oxidative stress, were also identified as downstream targets for PKC-3, and functioned in parallel with WTS-1 in the regulation of GO toxicity.ConclusionsUsing C. elegans as an in vivo assay system, we found that several developmental genes required for the control of intestinal development regulated both the intestinal permeability and the GO toxicity. With the focus on PKC-3, we raised two intestinal signaling cascades, PKC-3-SEC-8-WTS-1 and PKC-3-ISP-1/SOD-3. Our results will strengthen our understanding the molecular basis for developmental machinery of intestinal barrier against GO toxicity and translocation in animals.
Highlights
Intestinal barrier is crucial for animals against translocation of engineered nanomaterials (ENMs) into secondary targeted organs
Our previous study has indicated that acute exposure to graphene oxide (GO) at concentrations more than 10 mg/L could result in significant induction of intestinal reactive oxygen species (ROS) production and decrease in locomotion behavior in nematodes [28]
After acute exposure to GO, intestine-specific RNA interference (RNAi) knockdown of erm-1 or pkc-3 enhanced the induction of intestinal ROS production, and intestine-specific RNAi knockdown of act-5 suppressed the induction of intestinal ROS production (Fig. 1a)
Summary
Intestinal barrier is crucial for animals against translocation of engineered nanomaterials (ENMs) into secondary targeted organs. We investigated the molecular basis for intestinal barrier against toxicity and translocation of graphene oxide (GO) using C. elegans as a model animal. Graphene and its derivatives are two-dimensional carbon engineered nanomaterials (ENMs) with a single layer of sp2-bonded carbon atoms. They have the properties of chemical stability, high coefficient of thermal conduction, amphipathicity, large surface area, and ease of functionalization [1]. Intestinal barrier is very important for nematodes against ENMs toxicity and to block translocation of ENMs into secondary targeted organs [30, 36,37,38]. We hypothesized that deficit in intestinal development at certain aspects may alter the function of intestinal barrier and affect the toxicity and the translocation of GO in nematodes
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