1,4-Naphthoquinone Triggers Nematode Lethality by Inducing Oxidative Stress and Activating Insulin/IGF Signaling Pathway in Caenorhabditis elegans.

Jia Wang,Guangzhi Zeng,Xiaobing Huang,Ninghua Tan,Zhe Wang

doi:10.3390/molecules22050798

Abstract

Plant-parasitic nematodes are destructive pathogens causing enormous economic losses worldwide. With the withdrawal of fumigants, organophosphates and carbamates, pathogenic nematode control is more difficult. Phytochemicals are the plant secondary metabolites and are friendly for men and the environment. For developing new nematocidal candidates, we screened 790 phytochemicals using the model organism Caenorhabditis elegans and found 10 active compounds, 3 of which were further evaluated for their inhibitory activities against egg hatching of C. elegans and J2 Meloidogyne incognita. Among them, 1,4-naphthoquinone (1,4-NQ) was the only compound that could kill more than 50% of targets at 50 μg/mL, prompting us to investigate how 1,4-NQ triggers nematode lethality. In C. elegans, we observed that 1,4-NQ could influence reactive oxygen production, superoxide dismutase activity, and the heat-shock transcription factor (HSF)-1 pathway, which indicated that 1,4-NQ stimulated significant oxidative stress. Furthermore, using quantitative RT-PCR and transgenetic nematodes, we revealed that 1,4-NQ lethality was related to the Insulin/IGF signaling (IIS) pathway, and the effect of 1,4-NQ on IIS pathway related genes indicated that 1,4-NQ could activate this pathway and suppress the expression of DAF-16 target genes. The triggering of oxidative stress and activation of the IIS pathway indicated that 1,4-NQ operates through the generation of oxygen radicals, which can be lethal to C. elegans, thus making it an interesting lead compound for the development of future nematocides.

Highlights

Plant-parasitic nematode infections cause huge economic losses in global agriculture, which are estimated nearly at $157 billion annually [1,2]
The triggering of oxidative stress and activation of the Insulin/IGF signaling (IIS) pathway indicated that 1,4-NQ operates through the generation of oxygen radicals, which can be lethal to C. elegans, making it an interesting lead compound for the development of future nematocides
C. elegans as the model organism, we screened 790 phytochemicals against wild type N2 (N2) L4 worms at 50 μg/mL

Summary

Introduction

Plant-parasitic nematode infections cause huge economic losses in global agriculture, which are estimated nearly at $157 billion annually [1,2]. Synthetic nematocides, such as fumigants, organophosphates, and carbamates, are effective for nematode control, their use is becoming increasingly restricted due to their side effects to the environment and human health, increasing the demand for more sustainable nematocides [3]. Molecules 2017, 22, 798 organisms and biodegradability in a proper period of time [4]. Plants and their naturally occurring byproducts provide alternatives to synthetic nematocides. Phytochemicals are the plant’s secondary metabolites and they play a key role in nematocidal plants, including essential oils, triterpenoids, alkaloids, glucosinolates, and phenolics [5]

Methods

Results

Conclusion