Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

doi:10.1038/srep24024

Cited by 52 publications

(23 citation statements)

References 44 publications

(83 reference statements)

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“…Strikingly, egg‐laying and body size were the only parameters that were changed upon chronic exposure, while developmental timing, pharyngeal pumping, locomotion, and lifespan (bagging animals were censored from the population) stayed unaffected, which stands in contrast to previous GO toxicity studies in C. elegans . This discrepancy can be explained by differences between the physicochemical characteristics of GO, which has half the lateral size as compared to our study.…”

Section: Resultssupporting

confidence: 66%

“…Stress response mechanisms, including signaling pathways that regulate the innate immune response, are well‐conserved in C. elegans , and protect the animals from environmental stress, pathogens, viruses, toxins and heavy metals, making the worm a powerful model for complex human diseases . In recent years, the possible adverse effects of graphene on C. elegans have been investigated, resulting in considerable variations between the studies when measuring fecundity, development and lifespan, which might depend on the differences between the GO synthesis protocols and the specific treatment paradigm …”

Section: Introductionmentioning

confidence: 99%

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Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Rive

Reina

Wagle

et al. 2019

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Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. This study describes adverse effects of GO and amino‐functionalized GO (GONH2) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA‐Sequencing data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK‐1, which is a well‐established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk‐1 mutants show reduced tissue‐functionality and facultative vivipary. In a direct comparison, GONH2 exposure does not cause detrimental effects in the wild type or in pmk‐1 mutants, and the innate immune response is considerably less pronounced. This work establishes enhanced biocompatibility of amino‐functionalized GO in a whole‐organism, emphasizing its potential as a biomedical nanomaterial.

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Section: Resultssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Rive

Reina

Wagle

et al. 2019

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“…Exposure to GO could also induce cytotoxicity by activating the genuine autophagy35. Our previous studies in C. elegans have suggested that the insulin, JNK, apoptosis, and DNA damage signaling pathways are also involved in the control of GO toxicity242526. In this study, we observed that exposure to GO could affect the expression patterns of three Wnt ligands, CWN-1, CWN-2, and LIN-44, in nematodes (Fig.…”

Section: Discussionsupporting

confidence: 53%

“…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 nematodes242526. The Wnt signaling pathway is one of the evolutionarily conserved signal transduction pathways, and is extensively utilized during the development of animals and humans27.…”

mentioning

confidence: 99%

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

Zhi

Ren

et al. 2016

Sci Rep

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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.

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“…However, in a recent report, reduced graphene oxide (r‐GO) nanosheets showed little change in exploratory, anxiety‐like, or learning and memory behaviors, although general locomotor activity, balance and neuromuscular coordination were initially affected in mice (Zhang et al, ). A series of studies have suggested that nanomaterials elicit toxicity to C. elegans (Wang, ; Yang et al, ; Zhao et al, ). Wu et al () also observed a significant decrease in locomotion behavior in 10–100 mg l −1 GO‐exposed nematodes as reflected by endpoints of head thrash and body bend (Wu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage inCaenorhabditis elegans

et al. 2017

J. Appl. Toxicol.

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Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100 mg l GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub-lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene-based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle-frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat-4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene-based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene-based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene-based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd.

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Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

Cited by 52 publications

References 44 publications

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

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

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage inCaenorhabditis elegans

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