Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery

Abstract

BackgroundThe principal toxicity of acute organophosphate (OP) pesticide poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethality—particularly through the inhibition of AChE—studies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.ResultsWe exposed cultures of worms in axenic, defined medium to dichlorvos under three exposure protocols. In the first, worms were exposed continuously throughout the experiment. In the second and third, the worms were exposed for either 2 or 8 h, the dichlorvos was washed out of the culture, and the worms were allowed to recover. We then analyzed gene expression using whole genome microarrays from RNA obtained from worms sampled at multiple time points throughout the exposure. The worms showed a time-dependent increase in the expression of genes involved in stress responses. Early in the exposure, the predominant effect was on metabolic processes, while at later times, an immune-like response and cellular repair mechanisms dominated the expression pattern. Following removal of dichlorvos, the gene expression in the worms appeared to relatively rapidly return to steady-state levels.ConclusionThe changes in gene expression observed in the worms following exposure to dichlorvos point towards two potential mechanisms of toxicity: inhibition of AChE and mitochondrial disruption.

Mutations in Acetylcholinesterase2 (ace2) increase the insensitivity of acetylcholinesterase to fosthiazate in the root-knot nematode Meloidogyne incognita

“…Based on the results of the present study, the resistance of M. incognita to fosthiazate has been circumstantiated in tomato greenhouse, where chemical pest control strategies have been used for at least 7 years; however, the underlying molecular mechanism remains poorly understood. The fosthiazate-resistant population exhibited lower levels of AChE activity than the susceptible population, suggesting that a modified AChE might contribute to the reduced substrate affinity1721. RNAi results further confirmed that the ace 2 gene plays a major role in the interaction of AChE and fosthiazate, although mutation of ace 2 did not affect nematode infection.…”

“…In addition, mutations in at least 18 Caenorhabditis elegans genes were shown to confer resistance to the OP-like carbamate pesticide aldicarb20. Alterations of gene expression in C. elegans were found to be associated with organophosphate pesticide intoxication and recovery21. Class C of acetylcholinesterase of Meloidogyne had high affinity for acetylcholine, but was highly resistant to carbamate and organophosphate inhibitors2223.…”

The nematode Caenorhabditis elegans as an integrated toxicological tool to assess water quality and pollution

“…This aspect reinforces the concept that there must be other substances or chemicals in the water samples that were not detected a priori but even so exert weighty toxicological effects. Several reports showed that C. elegans was sensitive to different substances such as pesticides, heavy metals and toxins (Höss et al, 2013;Jiang et al, 2016;Lewis et al, 2013;Negga et al, 2011;Ruan et al, 2009;Yunhui et al, 2009). So it is possible that C. elegans toxicity could be explained by pollutants derived from the anthropogenic activities developed in the area (like agriculture, livestock and recreations).…”

WormNet v3: a network-assisted hypothesis-generating server for Caenorhabditis elegans

“…Finally, we tested a new context-centric prediction method, ‘find context-associated hub genes’, using toxicogenomics data derived from the exposure of C. elegans to the organophosphate pesticide, dichlorvos (17). The principle mechanism of acute toxicity by organophosphate pesticide is the inhibition of acetylcholinesterase.…”

“…We therefore conducted an analysis with 32 up-regulated genes (defined by >1.5-fold increase of expression levels after 26 h) and identified gene C14C10.1, which is a putative mitochondrial carrier protein, as the top candidate gene associated with prolonged intoxication by dichlorvos. Mitochondrial dysfunction has been suggested as a mechanism of intoxication (17) and many human diseases, such as metabolic disorders, neurodegenerative diseases, and muscle dystrophy, are associated with mutations of the mitochondrial carrier proteins (18). C14C10.1 may therefore represent a potential target for dichlorvos.…”