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1.
Chemosphere ; 261: 128162, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33113662

RESUMO

Microplastics, anthropogenically released into freshwaters, settle in sediments, where they are directly ingested by benthic organisms. However, to the best of our knowledge, fine-scale studies of microplastic ingestion and egestion by nematodes, one of the most abundant meiofaunal taxa, are lacking. We therefore conducted a time series of the ingestion and egestion by adult Caenorhabditis elegans and Pristionchus pacificus of 0.5- and 1.0-µm fluorescent polystyrene (PS) beads along with bacteria. The nematodes were exposed to 107 beads ml-1 in aqueous medium for 5 min-24 h and pumping rates of C. elegans were determined. In the egestion study, PS bead egestion was monitored in nematodes with high microplastic body burdens for 5 min-24 h in microplastic-free medium. Ingested beads were detected already within 5 min and up to 203 ± 15 PS beads (1.0 µm; C. elegans) were found after 30 min. Overall, significantly more 1.0-µm than 0.5-µm PS beads were taken up. The distinct feeding behaviors of the two species influenced their PS bead body burdens. Ingested PS beads were almost completely egested within the first 20-40 min in the presence of sufficient food. In C. elegans, 1.0-µm beads were egested less rapidly than 0.5-µm PS beads. Given the rapid ingestion and egestion of the beads, our study demonstrates that the actual amount of ingested and egested microplastics by nematodes in the environment may be several times higher than the microplastic body burdens may imply. However, spherical PS beads did not bioconcentrate in nematodes.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Microplásticos/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Bactérias , Exposição Dietética , Ingestão de Alimentos , Comportamento Alimentar , Água Doce , Microplásticos/análise , Poliestirenos/análise , Poliestirenos/farmacocinética , Poluentes Químicos da Água/análise
2.
Toxicol Lett ; 334: 102-109, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002525

RESUMO

Beauvericin is an ubiquitous mycotoxin with relevant occurrence in food and feed. It causes a high toxicity in several cell lines, but its general mechanism of action is not fully understood and only limited in vivo studies have been performed. We used Caenorhabditis elegans as a model organism to investigate effects of beauvericin. The mycotoxin displays a moderate acute toxicity at 100 µM; at this concentration also reproductive toxicity occurred (reduction of total progeny to 32.1 %), developmental toxicity was detectable at 250 µM. However, even lower concentrations were capable to reduce stress resistance and life span of the nematode: A significant reduction was detected at 10 µM beauvericin (decrease in mean survival time of 4.3 % and reduction in life span of 12.9 %). An increase in lipofuscin fluorescence was demonstrated starting at 10 µM suggesting oxidative stress as a mechanism of beauvericin toxicity. Beauvericin (100 µM) increases the number of apoptotic germ cells comparable to the positive control UV-C (400 J/m2). Conclusion: Low concentrations of beauvericin are capable to cause adverse effects in C. elegans, which may be relevant for hazard identification of this compound.


Assuntos
Apoptose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Depsipeptídeos/toxicidade , Células Germinativas/efeitos dos fármacos , Lipofuscina/metabolismo , Longevidade/efeitos dos fármacos , Micotoxinas/toxicidade , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Relação Dose-Resposta a Droga , Fertilidade/efeitos dos fármacos , Contaminação de Alimentos , Células Germinativas/patologia , Atividade Motora/efeitos dos fármacos , Testes de Toxicidade Aguda
3.
Ecotoxicol Environ Saf ; 203: 111001, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888585

RESUMO

Environmental nanomaterials contamination is a great concern for organisms including human. Copper oxide nanoparticles (CuO NPs) are widely used in a huge range of applications which might pose potential risk to organisms. This study investigated the in vivo transgenerational toxicity on development and reproduction with parental CuO NPs exposure in the nematode Caenorhabditis elegans. The results showed that CuO NPs (150 mg/L) significantly reduced the body length of parental C. elegans (P0). Only about 1 mg/L Cu2+ (~0.73%) were detected from 150 mg/L CuO NPs in 0.5X K-medium after 48 h. In transgenerational assays, CuO NPs (150 mg/L) parental exposure significantly induced developmental and reproductive toxicity in non-exposed C. elegans progeny (CuO NPs free) on body length (F1) and brood size (F1 and F2), respectively. In contrast, parental exposure to Cu2+ (1 mg/L) did not cause transgenerational toxicity on growth and reproduction. This suggests that the transgenerational toxicity was mostly attributed to the particulate form of CuO NPs. Moreover, qRT-PCR results showed that the mRNA levels of met-2 and spr-5 genes were significantly decreased at P0 and F1 upon only maternal exposure to CuO NPs (150 mg/L), suggesting the observed transgenerational toxicity was associated with possible epigenetic regulation in C. elegans.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Cobre/toxicidade , Epigênese Genética/efeitos dos fármacos , Nanopartículas/toxicidade , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Feminino , Humanos , Exposição Materna/efeitos adversos , Reprodução/efeitos dos fármacos , Reprodução/genética
4.
Chemosphere ; 254: 126909, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957299

RESUMO

Soil contamination by heavy metals (HMs) is an environmental problem, and nanoremediation by using zero-valent iron nanoparticles (nZVI) has attracted increasing interest. We used ecotoxicological test and global transcriptome analysis with DNA microarrays to assess the suitability of C. elegans as a useful bioindicator to evaluate such strategy of nanoremediation in a highly polluted soil with Pb, Cd and Zn. The HMs produced devastating effect on C. elegans. nZVI treatment reversed this deleterious effect up to day 30 after application, but the reduction in the relative toxicity of HMs was lower at day 120. We stablished gene expression profile in C. elegans exposed to the polluted soil, treated and untreated with nZVI. The percentage of differentially expressed genes after treatment decreases with exposure time. After application of nZVI we found decreased toxicity, but increased biosynthesis of defensive enzymes responsive to oxidative stress. At day 14, when a decrease in toxicity has occurred, genes related to specific heavy metal detoxification mechanisms or to response to metal stress, were down regulated: gst-genes, encoding for glutathione-S-transferase, htm-1 (heavy metal tolerance factor), and pgp-5 and pgp-7, related to stress response to metals. At day 120, we found increased HMs toxicity compared to day 14, whereas the transcriptional oxidative and metal-induced responses were attenuated. These findings indicate that the profiled gene expression in C. elegans may be considered as an indicator of stress response that allows a reliable evaluation of the nanoremediation strategy.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Ferro/química , Metais Pesados/toxicidade , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Poluentes do Solo/toxicidade , Transcrição Genética/efeitos dos fármacos , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Ecotoxicologia , Nanopartículas Metálicas , Metais Pesados/análise , Estresse Oxidativo/genética , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise , Toxicogenética
5.
PLoS One ; 15(9): e0238637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903270

RESUMO

Neonicotinoids, a class of insecticides structurally similar to nicotine that target biting and sucking insects, are the most widely used insecticides today, in part due to their supposed low toxicity in other organisms. However, a growing body of research has found that even low doses of neonicotinoids can induce unexpected negative effects on the physiology and survival of a wide range of non-target organisms. Importantly, no work has been done on the commercial formulations of pesticides that include imidacloprid as the active ingredient, but that also contain many other components. The present study examines the sublethal effects of "Tree and Shrub"™ ("T+S"), a commercial insecticide containing the neonicotinoid imidacloprid as its active ingredient, on Caenorhabditis elegans. We discovered that "T+S" significantly stunted the overall growth in wildtype nematodes, an effect that was exacerbated by concurrent exposure to heat stress. "T+S" also negatively impacted fecundity as measured by increased germline apoptosis, a decrease in egg-laying, and fewer viable offspring. Lastly, exposure to "T+S" resulted in degenerative changes in nicotinic cholinergic neurons in wildtype nematodes. As a whole, these findings demonstrate widespread toxic effects of neonicotinoids to critical functions in nematodes.


Assuntos
Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Inseticidas/toxicidade , Locomoção/efeitos dos fármacos , Neonicotinoides/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/metabolismo , Aberrações Cromossômicas , Fertilidade/efeitos dos fármacos , Células Germinativas/citologia , Células Germinativas/efeitos dos fármacos , Resposta ao Choque Térmico , Degeneração Neural/patologia , Oviposição/efeitos dos fármacos , Reprodução/efeitos dos fármacos
6.
PLoS One ; 15(9): e0238528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881908

RESUMO

Quercetin is a yellow pigment that is found in many common dietary plants, and that protects against oxidative stress, inflammation, and arteriosclerosis. It has also been suggested to prolong the lifespan of, and enhance heat-stress tolerance in nematodes; thus, the present study investigated its effects on both the nematode life- and health span by assessing its capacity to promote nematode motility after aging and/or heat stress, as well as the mechanisms underlying these effects. The results of the conducted analyses showed that quercetin feeding prolonged lifespan, suppressed age-related motility retardation, improved motility recovery after heat stress, and decreased the production of both intercellular and mitochondrial reactive oxygen species in the analysed Caenorhabditis elegans strains, likely by modulating the insulin-like signalling (ILS) pathway and p38-mitogen-activated protein kinase (MAPK) pathway. In particular, the transcription factors DAF-16 and SKN-1 were found to mediate the observed quercetin-induced effects, consistent with their previously demonstrated roles as regulators of aging. Furthermore, we demonstrated, for the first time, that quercetin induced heat-stress tolerance in C. elegans by modulating HSF-1 expression and/or activity. Thus, the present study provides valuable insights into the mechanisms by which quercetin inhibit aging and enhance heat-stress tolerance via ILS and MAPK pathway in C. elegans.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Quercetina/farmacologia , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Int J Nanomedicine ; 15: 5227-5237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801688

RESUMO

Background: Large-scale production and application of amorphous silica nanoparticles (SiNPs) have enhanced the risk of human exposure to SiNPs. However, the toxic effects and the underlying biological mechanisms of SiNPs on Caenorhabditis elegans remain largely unclear. Purpose: This study was to investigate the genome-wide transcriptional alteration of SiNPs on C. elegans. Methods and Results: In this study, a total number of 3105 differentially expressed genes were identified in C. elegans. Among them, 1398 genes were significantly upregulated and 1707 genes were notably downregulated in C. elegans. Gene ontology analysis revealed that the significant change of gene functional categories triggered by SiNPs was focused on locomotion, determination of adult lifespan, reproduction, body morphogenesis, multicellular organism development, endoplasmic reticulum unfolded protein response, oocyte development, and nematode larval development. Meanwhile, we explored the regulated effects between microRNA and genes or signaling pathways. Pathway enrichment analysis and miRNA-gene-pathway-network displayed that 23 differential expression microRNA including cel-miR-85-3p, cel-miR-793, cel-miR-241-5p, and cel-miR-5549-5p could regulate the longevity-related pathways and inflammation signaling pathways, etc. Additionally, our data confirmed that SiNPs could disrupt the locomotion behavior and reduce the longevity by activating ins-7, daf-16, ftt-2, fat-5, and rho-1 genes in C. elegans. Conclusion: Our study showed that SiNPs induced the change of the whole transcriptome in C. elegans, and triggered negative effects on longevity, development, reproduction, and body morphogenesis. These data provide abundant clues to understand the molecular mechanisms of SiNPs in C. elegans.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Nanopartículas/toxicidade , Animais , Proteínas de Caenorhabditis elegans/genética , Redes Reguladoras de Genes/efeitos dos fármacos , Genoma Helmíntico , Humanos , Longevidade/efeitos dos fármacos , MicroRNAs/genética , Testes de Mutagenicidade/métodos , Nanopartículas/química , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Transcriptoma , Resposta a Proteínas não Dobradas/genética
8.
Proc Natl Acad Sci U S A ; 117(29): 17142-17150, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32636256

RESUMO

Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli, extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPRmt). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans , Fatores de Transcrição Forkhead/metabolismo , Longevidade/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Aldeído Pirúvico , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Escherichia coli/metabolismo , Microbioma Gastrointestinal/fisiologia , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Modelos Biológicos , Aldeído Pirúvico/metabolismo , Aldeído Pirúvico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genética
9.
Adv Exp Med Biol ; 1207: 681-688, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671785

RESUMO

Senescence is a progressive process of degeneration that occurs when cells and organisms mature. Many studies have shown that autophagy is closely related to senescence. Autophagy gradually decreases with the senescence activity of cells, and vice versa. Therefore, moderate autophagy can protect the body and inhibit cell senescence. The inactivation of genes encoding nematode insulin-like tyrosine kinase receptor (daf-2) inhibited the activity of type I PI3K (age-1), Akt molecules (akt1, akt2), PDK (pdk-1), and TOR, and increased the lifespan and autophagy of Caenorhabditis elegans.


Assuntos
Envelhecimento/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Humanos , Longevidade/efeitos dos fármacos
10.
Chemosphere ; 261: 127756, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32731027

RESUMO

Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-approved drugs using a simple assay in the nematode C. elegans and found three compounds that caused morphological changes. While the anticoagulant ticlopidine and the antifungal sertaconazole caused both accumulations that resulted in distinct distortions of pharyngeal anatomy and lethality upon acute exposure, the proton-pump inhibitor dexlansoprazole caused molting defects and required exposure during larval development. Such easily detectable defects in a powerful genetic model system advocate the continued exploration of current medicines using a variety of model organisms to better understand drugs already prescribed to millions of patients.


Assuntos
Bioacumulação/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Dexlansoprazol/toxicidade , Imidazóis/toxicidade , Muda/efeitos dos fármacos , Tiofenos/toxicidade , Ticlopidina/toxicidade , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Dexlansoprazol/metabolismo , Aprovação de Drogas , Epigênese Genética/efeitos dos fármacos , Humanos , Imidazóis/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Mutação , Tiofenos/metabolismo , Ticlopidina/metabolismo , Estados Unidos , United States Food and Drug Administration
11.
Ecotoxicol Environ Saf ; 201: 110857, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32534332

RESUMO

Caenorhabditis elegans is sensitive to toxicity of environmental pollutants. The alteration in expression of mir-794, a microRNA (miRNA) molecule, mediated a protective response to nanopolystyene (100 nm) at predicted environmental concentration (1 µg/L) in nematodes. However, the underlying molecular basis for mir-794 function in regulating the response to nanopolystyrene remains largely unclear. In this study, we found that intestinal overexpression of mir-794 caused the susceptibility to nanopolystyrene toxicity, suggesting that mir-794 acted in the intestine to regulate the response to nanopolystyrene. Intestinal overexpression of mir-794 further decreased the expressions of daf-16 encoding a FOXO transcriptional factor in insulin signaling pathway, skn-1 encoding a Nrf transcriptional factor in p38 MAPK signaling pathway, and mdt-15 encoding a lipid metabolic sensor acting downstream of SKN-1 in nanopolystyrene exposed nematodes. Meanwhile, intestinal overexpression of mir-794 could suppress the resistance of nematodes overexpressing intestinal daf-16, skn-1, or mdt-15 containing the corresponding 3' untranslated region (3' UTR) to nanopolystyrene toxicity. Therefore, DAF-16, SKN-1, and MDT-15 acted as the downstream targets of intestinal mir-794 to regulate the response to nanopolystyrene. In the intestine, DAF-16 functioned synergistically with SKN-1 or MDT-15 to regulate the response to nanopolystyrene. Our results suggested that the intestinal mir-794 provided an important epigenetic regulation mechanism to control the response to nanopolystyrene by linking insulin and p38 MAPK signaling pathways in nematodes.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Insulina/metabolismo , Intestinos/efeitos dos fármacos , MicroRNAs/metabolismo , Nanopartículas/toxicidade , Poliestirenos/toxicidade , Poluentes do Solo/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Epigênese Genética , Regulação da Expressão Gênica , Lipídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , MicroRNAs/genética , Fatores de Transcrição/genética
12.
PLoS Genet ; 16(6): e1008829, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32502151

RESUMO

Ion channels are present at specific levels within subcellular compartments of excitable cells. The regulation of ion channel trafficking and targeting is an effective way to control cell excitability. The BK channel is a calcium-activated potassium channel that serves as a negative feedback mechanism at presynaptic axon terminals and sites of muscle excitation. The C. elegans BK channel ortholog, SLO-1, requires an endoplasmic reticulum (ER) membrane protein for efficient anterograde transport to these locations. Here, we found that, in the absence of this ER membrane protein, SLO-1 channels that are seemingly normally folded and expressed at physiological levels undergo SEL-11/HRD1-mediated ER-associated degradation (ERAD). This SLO-1 degradation is also indirectly regulated by a SKN-1A/NRF1-mediated transcriptional mechanism that controls proteasome levels. Therefore, our data indicate that SLO-1 channel density is regulated by the competitive balance between the efficiency of ER trafficking machinery and the capacity of ERAD.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas de Ligação a DNA/metabolismo , Degradação Associada com o Retículo Endoplasmático/genética , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Terminações Pré-Sinápticas/metabolismo , Fatores de Transcrição/metabolismo , Aldicarb/farmacologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Acoplamento Excitação-Contração/efeitos dos fármacos , Acoplamento Excitação-Contração/genética , Retroalimentação Fisiológica/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Músculos/inervação , Terminações Pré-Sinápticas/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma , Isoformas de Proteínas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
13.
Nature ; 583(7816): 415-420, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555456

RESUMO

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts2,3. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine ß-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.


Assuntos
Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Comportamento Alimentar/fisiologia , Intestinos/microbiologia , Neurotransmissores/metabolismo , Providencia/metabolismo , Olfato/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Microbioma Gastrointestinal/fisiologia , Metabolômica , Mutação , Octanóis/farmacologia , Octopamina/biossíntese , Octopamina/metabolismo , Providencia/enzimologia , Providencia/fisiologia , Receptores de Amina Biogênica/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Células Receptoras Sensoriais/metabolismo , Olfato/efeitos dos fármacos , Tiramina/biossíntese , Tiramina/metabolismo
14.
Food Chem ; 330: 127228, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535316

RESUMO

Betalain-rich extracts have been used for many years by their nutraceutical potential. However, the study of their bioactivities has always been hampered by their difficult obtention. To explain their mode of action, seventeen pure betalains were tested in vivo using the animal model C. elegans. Four betalains, named indicaxanthin, indoline carboxylic acid-betacyanin, phenylalanine-betaxanthin, and dopaxanthin, behaved as extraordinary in vivo antioxidants and anti-aging compounds, by increasing the lifespan of C. elegans up to 16.82%, 16.65%, 16.53%, and 12.93%, respectively. The first microarrays performed with betalains and biological confirmation with different mutant strains showed that this life extension is due to a reduction of oxidative stress and the activation of the transcription factors DAF-16/FOXO and SKN-1/Nrf2. They are involved in longevity and oxidative stress resistance pathways and lead to overexpression of HSPs genes, involved in resistance to cancer and Alzheimer's, opening novel research lines in the search for effective plant-based treatments.


Assuntos
Betalaínas/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Longevidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fatores de Transcrição/metabolismo
15.
Chemosphere ; 256: 127172, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32470744

RESUMO

Nanoplastic exposure could cause toxicity to Caenorhabditis elegans at various aspects. Nevertheless, the effects of chronic exposure to nanoplastics remain largely unclear in nematodes. In this study, we employed C. elegans as an animal model to determine the effects of nanopolystyrene (30 nm) exposure from adult day-1 for 8-day. After the exposure, only 1000 µg/L nanopolystyrene reduced the lifespan. In contrast, nanopolystyrene ≥1 µg/L decreased locomotion behavior and activated oxidative stress. Meanwhile, in 10 µg/L nanopolystyrene exposed nematodes, both expression of SOD-3, a Mn-SOD, and autophagy induction as indicated by LGG-1:GFP expression were significantly increased. RNAi knockdown of daf-2 encoding an insulin receptor enhanced the autophagy induction, and RNAi knockdown of daf-16 encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the autophagy induction in 10 µg/L nanopolystyrene exposed nematodes. Moreover, DAF-16 acted upstream of LGG-1, an ortholog of Atg8/LC3, to regulate the toxicity of nanopolystyrene toxicity in inducing ROS production and in decreasing locomotion behavior at adult day-9. Our data implied the potential toxicity of chronic exposure to nanoplastics at predicted environmental concentrations on organisms.


Assuntos
Autofagia/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poliestirenos/toxicidade , Animais , Proteínas de Caenorhabditis elegans/biossíntese , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição Forkhead/genética , Insulina/metabolismo , Locomoção/genética , Longevidade , Modelos Animais , Interferência de RNA , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transdução de Sinais , Superóxido Dismutase/biossíntese
16.
Nat Commun ; 11(1): 2099, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350248

RESUMO

Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17-MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/imunologia , Caenorhabditis elegans/fisiologia , Imunidade , Interleucina-17/metabolismo , Longevidade , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , Neurônios/metabolismo , Animais , Comportamento Animal , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Fluorescência Verde/metabolismo , Imunidade/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Interneurônios/fisiologia , Longevidade/efeitos dos fármacos , Modelos Biológicos , Neurônios/efeitos dos fármacos , Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Frações Subcelulares/metabolismo , Transgenes
17.
Int J Nanomedicine ; 15: 3217-3233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440120

RESUMO

Introduction: Since CdTe quantum dots (QDs) are still widely considered as advanced fluorescent probes because of their far superior optical performance and fluorescence efficiency over non-cadmium QDs, it is important to find ways to control their toxicity. Methods: In this study, the adverse effects of two cadmium-containing QDs, ie, CdTe QDs and CdTe@ZnS QDs, on the nervous system of nematode C. elegans, the hippocampus of mice, and cultured microglia were measured in order to evaluate the neuroinflammation caused by cadmium-containing QDs and the potential mechanisms. Results: Firstly, we observed that cadmium-containing QD exposure-induced immune responses and neurobehavioral deficit in nematode C. elegans. In the mice treated with QDs, neuroinflammatory responses to QDs in the hippocampus, including microglial activation and IL-1ß release, occurred as well. When investigating the mechanisms of cadmium-containing QDs causing IL-1ß-mediated inflammation, the findings suggested that cadmium-containing QDs activated the NLRP3 inflammasome by causing excessive ROS generation, and resulted in IL-1ß release. Discussion: Even though the milder immune responses and neurotoxicity of CdTe@ZnS QDs compared with CdTe QDs indicated the protective role of ZnS coating, the inhibitions of NLRP3 expression and ROS production completely reduced the IL-1ß-mediated inflammation. This provided valuable information that inhibiting target molecules is an effective and efficient way to alleviate  the toxicity of cadmium-containing QDs, so it is important to evaluate QDs through a mechanism-based risk assessment.


Assuntos
Encéfalo/patologia , Compostos de Cádmio/farmacologia , Inflamação/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pontos Quânticos/química , Sulfetos/farmacologia , Telúrio/farmacologia , Compostos de Zinco/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/imunologia , Linhagem Celular , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos ICR , Microglia/efeitos dos fármacos , Microglia/patologia , Espécies Reativas de Oxigênio/metabolismo
18.
Nat Commun ; 11(1): 2587, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444616

RESUMO

The gut microbiota metabolizes drugs and alters their efficacy and toxicity. Diet alters drugs, the metabolism of the microbiota, and the host. However, whether diet-triggered metabolic changes in the microbiota can alter drug responses in the host has been largely unexplored. Here we show that dietary thymidine and serine enhance 5-fluoro 2'deoxyuridine (FUdR) toxicity in C. elegans through different microbial mechanisms. Thymidine promotes microbial conversion of the prodrug FUdR into toxic 5-fluorouridine-5'-monophosphate (FUMP), leading to enhanced host death associated with mitochondrial RNA and DNA depletion, and lethal activation of autophagy. By contrast, serine does not alter FUdR metabolism. Instead, serine alters E. coli's 1C-metabolism, reduces the provision of nucleotides to the host, and exacerbates DNA toxicity and host death without mitochondrial RNA or DNA depletion; moreover, autophagy promotes survival in this condition. This work implies that diet-microbe interactions can alter the host response to drugs without altering the drug or the host.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Floxuridina/toxicidade , Interações Alimento-Droga , Microbioma Gastrointestinal/efeitos dos fármacos , Serina/farmacologia , Animais , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Suplementos Nutricionais , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Floxuridina/farmacocinética , Ácido Fólico/metabolismo , Microbioma Gastrointestinal/fisiologia , Timidina/análogos & derivados , Timidina/metabolismo , Timidina/farmacocinética , Timidina/farmacologia , Nucleotídeos de Uracila/metabolismo , Nucleotídeos de Uracila/farmacocinética
19.
J Vis Exp ; (158)2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32420986

RESUMO

C. elegans is commonly used to model age-related neurodegenerative diseases caused by repeat expansion mutations, such as Amyotrophic Lateral Sclerosis (ALS) and Huntington's disease. Recently, repeat expansion-containing RNA was shown to be the substrate for a novel type of protein translation called repeat-associated non-AUG-dependent (RAN) translation. Unlike canonical translation, RAN translation does not require a start codon and only occurs when repeats exceed a threshold length. Because there is no start codon to determine the reading frame, RAN translation occurs in all reading frames from both sense and antisense RNA templates that contain a repeat expansion sequence. Therefore, RAN translation expands the number of possible disease-associated toxic peptides from one to six. Thus far, RAN translation has been documented in eight different repeat expansion-based neurodegenerative and neuromuscular diseases. In each case, deciphering which RAN products are toxic, as well as their mechanisms of toxicity, is a critical step towards understanding how these peptides contribute to disease pathophysiology. In this paper, we present strategies to measure the toxicity of RAN peptides in the model system C. elegans. First, we describe procedures for measuring RAN peptide toxicity on the growth and motility of developing C. elegans. Second, we detail an assay for measuring postdevelopmental, age-dependent effects of RAN peptides on motility. Finally, we describe a neurotoxicity assay for evaluating the effects of RAN peptides on neuron morphology. These assays provide a broad assessment of RAN peptide toxicity and may be useful for performing large-scale genetic or small molecule screens to identify disease mechanisms or therapies.


Assuntos
Caenorhabditis elegans/crescimento & desenvolvimento , Expansão das Repetições de DNA , Neurônios/patologia , Iniciação Traducional da Cadeia Peptídica , Fragmentos de Peptídeos/toxicidade , RNA Antissenso/genética , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Neurônios/efeitos dos fármacos
20.
Oxid Med Cell Longev ; 2020: 7509612, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273948

RESUMO

Glutamic acid (Glu) is a worldwide flavor enhancer with various positive effects. However, Glu-induced neurotoxicity has been reported less. Tetrastigma hemsleyanum (TH), a rare herbal plant in China, possesses high medicinal value. More studies paid attention to tuber of TH whereas vine part (THV) attracts fewer focus. In this study, we extracted and purified flavones from THV (THVF), and UPLC-TOF/MS showed THVF was consisted of 3-caffeoylquinic acid, 5-caffeoylquinic acid, quercetin-3-O-rutinoside, and kaempferol-3-O-rutinoside. In vitro, Glu caused severe cytotoxicity, genotoxicity, mitochondrial dysfunction, and oxidative damage to rat phaeochromocytoma (PC12) cells. Conversely, THVF attenuated Glu-induced toxicity via MAPK pathways. In vivo, the neurotoxicity triggered by Glu restrained the athletic ability in Caenorhabditis elegans (C. elegans). The treatment of THVF reversed the situation induced by Glu. In a word, Glu could cause neurotoxicity and THVF owns potential neuroprotective effects both in vitro and in vivo via MAPK pathways.


Assuntos
Antioxidantes/química , Caenorhabditis elegans/efeitos dos fármacos , Ácido Glutâmico/efeitos adversos , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos dos fármacos , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/química , Folhas de Planta/química , Vitaceae/química , Animais , Flavonas , Humanos , Ratos
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