Wnt Ligands Differentially Regulate Toxicity and Translocation of Graphene Oxide through Different Mechanisms in Caenorhabditis elegans.

Hanyu Zhang,Dayong Wang,Mingxia Ren,Man Qu,Lingtong Zhi

doi:10.1038/srep39261

Abstract

In this study, we investigated the possible involvement of Wnt signals in the control of graphene oxide (GO) toxicity using the in vivo assay system of Caenorhabditis elegans. In nematodes, the Wnt ligands, CWN-1, CWN-2, and LIN-44, were found to be involved in the control of GO toxicity. Mutation of cwn-1 or lin-44 gene induced a resistant property to GO toxicity and resulted in the decreased accumulation of GO in the body of nematodes, whereas mutation of cwn-2 gene induces a susceptible property to GO toxicity and an enhanced accumulation of GO in the body of nematodes. Genetic interaction assays demonstrated that mutation of cwn-1 or lin-44 was able to suppress the susceptibility to GO toxicity shown in the cwn-2 mutants. Loss-of-function mutations in all three of these Wnt ligand genes resulted in the resistance of nematodes to GO toxicity. Moreover, the Wnt ligands might differentially regulate the toxicity and translocation of GO through different mechanisms. These findings could be important in understanding the function of Wnt signals in the regulation of toxicity from environmental nanomaterials.

Highlights

Up to this point, the classic animal model Caenorhabditis elegans has been widely used in the assessment of toxicity and toxicological studies of environmental toxicants, including the engineered nanomaterials (ENMs)[13,14,15,16]
In order to determine the role of CWN-1, CWN-2, MOM-2, EGL-20, or LIN-44 in the regulation of graphene oxide (GO) toxicity, we investigated the effects of cwn-1, cwn-2, mom-2, egl-20, or lin-44 mutation on GO toxicity in nematodes
After GO (100 mg/L) exposure, we found that mutation of cwn-1 or lin-44 gene induced a resistant property to GO toxicity, whereas mutation of cwn-2 gene induced a susceptible property to GO toxicity, using intestinal reactive oxygen species (ROS) production and locomotion behavior as the endpoints (Fig. 1)

Summary

Introduction

The classic animal model Caenorhabditis elegans has been widely used in the assessment of toxicity and toxicological studies of environmental toxicants, including the engineered nanomaterials (ENMs)[13,14,15,16]. C. elegans make a useful model in elucidating the molecular mechanism of toxicity induction of ENMs in other organism due to the conservation of the basic stress response and molecular signaling pathways with mammals and humans[23]. A few important signaling pathways, including insulin, c-Jun N-terminal kinase (JNK), apoptosis, and DNA damage signaling pathways have already been shown to be involved in the control of GO toxicity in nematodes[24,25,26]. In C. elegans, the Wnt signals are involved in controlling different aspects of development, including the proliferation, fate specification, and polarity[28]. The potential important role of Wnt signals in the regulation of GO toxicity in nematodes was investigated. Out data suggests that the Wnt signals might act through different mechanisms in the regulation of GO toxicity in nematodes

Methods

Results

Conclusion