Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

J of Applied Toxicology

et al. 2015

Acrylamide can form in foods during the cooking process and cause multiple adverse effects. However, the neurotoxicity and mechanisms of acrylamide have not been fully elucidated. In Caenorhabditis elegans, we showed that 48 h exposure to 10-625 mg l(-1) acrylamide resulted in a significant decline in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, acrylamide exposure reduced crawling speeds and changed angles of body bending. It indicates that acrylamide induces locomotor defects, along with parkinsonian-like movement impairment, including bradykinesia and hypokinesia. Acrylamide also affected chemotaxis plasticity and reduced learning ability. Using transgenic nematodes, we found that acrylamide induced downexpression of P(dat-1) and led to the degeneration of dopaminergic neurons. Moreover, the enhanced expression of unc-54, encoding a subunit of α-synuclein was found. It illustrates that acrylamide is efficient in inducing crucial parkinsonian pathology, including dopaminergic damage and α-synuclein aggregation. These findings suggest the acrylamide-induced locomotor defects and neurotoxicity are associated with Parkinson's disease.

Section: Introductionmentioning

confidence: 97%

Acrylamide induces locomotor defects and degeneration of dopamine neurons in Caenorhabditis elegans

Li¹,

Li²,

J of Applied Toxicology

et al. 2015

“…Using C. elegans , previous studies have suggested the GO toxicity on the functions of both primary (such as intestine) and secondary (such as neuron and reproductive organs) targeted organs15161718. Regarding the cellular mechanisms of GO toxicity, the published data have suggested that GO toxicity might be consequent to the bioavailability, induction of reactive oxygen species (ROS), enhanced intestinal permeability, disrupted innate immune response, and prolonged defecation cycle length in nematodes16171920. Previous studies have also implied the crucial role of intestinal biological barrier against GO toxicity in nematodes1721.…”

mentioning

confidence: 99%

“…Regarding the cellular mechanisms of GO toxicity, the published data have suggested that GO toxicity might be consequent to the bioavailability, induction of reactive oxygen species (ROS), enhanced intestinal permeability, disrupted innate immune response, and prolonged defecation cycle length in nematodes16171920. Previous studies have also implied the crucial role of intestinal biological barrier against GO toxicity in nematodes1721. It has also been reported that the induction of oxidative stress might play a key role in the chemical mechanism for GO induced shortened longevity in exposed nematodes15.…”

mentioning

confidence: 99%

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

Zhao

Rui

et al. 2016

Sci Rep

Self Cite

Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

“…The classic model animal of nematode Caenorhabditis elegans is an important non-mammalian alternative for toxicological study67. Previous studies using nematodes have demonstrated that GO exposure could lead to toxic effects on the functions of both primary (such as intestine) and secondary (such as neuron and reproductive organs) targeted organs8910111213. Furthermore, the activation of oxidative stress, enhanced intestinal permeability, disrupted innate immune response, and prolonged defecation cycle length were found to contribute to the formation of GO toxicity in nematodes91011.…”

mentioning

confidence: 99%

A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

Ren

Rui

et al. 2016

Sci Rep

Self Cite

Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.