58 Papers found (0.011 seconds)

Li PM et al. (1991) Proc Natl Acad Sci U S A "The LIM region of a presumptive Caenorhabditis elegans transcription factor is an iron-sulfur- and zinc-containing metallodomain."

Freyd G, Horvitz HR, Li PM, Walsh CT, Reichert J

[

Proc Natl Acad Sci U S A,

1991]

The cysteine-rich LIM motif is highly conserved between invertebrates and mammals. This motif shows similarity both to proteins that bind zinc and to ferredoxins, which contain iron-sulfur clusters. Two tandem copies of the LIM motif are found in a number of presumptive transcription factors, including the protein product of the Caenorhabditis elegans cell-lineage gene lin-11. To investigate the possible metal-binding properties of the LIM region of the lin-11 protein, we expressed and purified a 151-amino acid peptide containing the tandem LIM motifs. The purified peptide binds both zinc (two atoms per protein molecule) and iron (as a redox-active iron-sulfur cluster, with four atoms of iron and four atoms of inorganic sulfide per protein molecule). These observations suggest that the LIM motif is a metallodomain that might function in a redox-sensitive regulation of transcription.

Liu X et al. (2022) Chemosphere "Ecotoxicity induced by total, water soluble and insoluble components of atmospheric fine particulate matter exposure in Caenorhabditis elegans."

Lu Z, Yan Z, Liu X, Cao M, Ge P, Chen M, Wang J, Chen W

[

Chemosphere,

2022]

Although PM2.5 could cause toxicity in environmental organisms, the toxicity difference of PM2.5 under different solubilities is still poorly understood. To acquire a better knowledge of the ecotoxicity of PM2.5 under different solubilities, the model animal Caenorhabditis elegans (C. elegans) was exposed to Total-PM2.5, water insoluble components of PM2.5 (WIS-PM2.5) and water soluble components of PM2.5 (WS-PM2.5). The physiological (growth, locomotion behavior, and reproduction), biochemical (germline apoptosis, and reactive oxygen species (ROS) production) indices, and the related gene expression were examined. According to the findings, acute exposure to these three components caused adverse physiological effects on growth and locomotion behavior, and significantly induced germline apoptosis or ROS production. In contrast, prolonged exposure showed stronger adverse effects than acute exposure. Additionally, the results of multiple toxicological endpoints showed that the toxicity effects of WIS-PM2.5 are more intense than WS-PM2.5, which means that insoluble components contributed more to the toxicity of PM2.5. Prolonged exposure to 1000 mg/L WS-PM2.5, WIS-PM2.5, and Total-PM2.5 dramatically altered the expression of stress-related genes, which further indicated that apoptosis, DNA damage and oxidative stress play a crucial part in toxicity induced by PM2.5.

Gopal E et al. (2015) J Pharmacol Exp Ther "Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates."

Ganapathy V, Ramachandran S, Gopal E, Babu E, Prasad PD, Bhutia YD

[

J Pharmacol Exp Ther,

2015]

NaCT (SLC13A5) is a Na(+)-coupled transporter for Krebs cycle intermediates and is expressed predominantly in the liver. Human NaCT is relatively specific for citrate compared with other Krebs cycle intermediates. The transport activity of human NaCT is stimulated by Li(+), whereas that of rat NaCT is inhibited by Li(+). We studied the influence of Li(+) on NaCTs cloned from eight different species. Li(+) stimulated the activity of only NaCTs from primates (human, chimpanzee, and monkey); by contrast, NaCTs from nonprimate species (mouse, rat, dog, and zebrafish) were inhibited by Li(+). Caenorhabditis elegans NaCT was not affected by Li(+). With human NaCT, the Li(+)-induced increase in transport activity was associated with the conversion of the transporter from a low-affinity/high-capacity type to a high-affinity/low-capacity type. H(+) was able to substitute for Li(+) in eliciting the stimulatory effect. The amino acid Phe500 in human NaCT was critical for Li(+)/H(+)-induced stimulation. Mutation of this amino acid to tryptophan (F500W) markedly increased the basal transport activity of human NaCT in the absence of Li(+), but the ability of Li(+) to stimulate the transporter was almost completely lost with this mutant. Substitution of Phe500 with tryptophan in human NaCT converted the transporter from a low-affinity/high-capacity type to a high-affinity/low-capacity type, an effect similar to that of Li(+) on the wild-type NaCT. These studies show that Li(+)-induced activation of NaCT is specific for the transporter in primates and that the region surrounding Phe500 in primate NaCTs is important for the Li(+) effect.

Kim JY et al. (2020) Biotechnol Lett "Protective effect of Lactobacillus casei HY2782 against particulate matter toxicity in human intestinal CCD-18Co cells and Caenorhabditis elegans."

Sim JH, Kim MR, Jung SH, Kim JY, Lee SY, Choi ID, Kang K, Pan CH, Lee JL

[

Biotechnol Lett,

2020]

OBJECTIVES: To investigate the preventive effect of Lactobacillus casei HY2782 on toxicity induced by particulate matter (PM, inhalable particles less than 10 m in diameter) in human intestinal CCD-18Co cells and a model animal Caenorhabditis elegans. RESULTS: L. casei HY2782 treatment prevented PM-induced intestinal cell death via cellular reactive oxygen species production and membrane disruption attenuation. PM significantly decreased the total number of eggs laid and the body bending activity of C. elegans, demonstrating PM toxicity. L. casei HY2782 treatment restored the reproductive toxicity and decline in locomotion activity induced by PM in C. elegans. Overall, L. casei HY2782 attenuated PM toxicity in vitro in cultured intestinal cells and in vivo in the model nematode. CONCLUSION: Our study provides a potential clue for developing L. casei HY2782 probiotics that attenuate PM-induced cellular and physiological toxicity; however, further in-depth preclinical trials using mammalian animal models and clinical trials are required.

Caceres Quijano MF et al. (2021) Chemosphere "Assessment of the effects of seasonality on the ecotoxicity induced by the particulate matter using the animal model Caenorhabditis elegans."

Caceres Quijano MF, Santa-Helena E, De Falco A, Gioda CR, Josende ME, de Paula Ribeiro J, Gioda A

[

Chemosphere,

2021]

The present work aimed to establish potential changes in the ecotoxicological effects on C. elegans induced by the exposure of coarse (PM10) and fine (PM2.5) particulate matter collected during dry and rainy periods. We also analyzed the probable influence on the change of a city's activities as the mega-events result in air quality. The element levels evaluation was performed on PM, on the solutions of exposure, and C. elegans after exposure. Biochemical essays were performed to evaluate damage to C. elegans. The results showed that infrastructure works increased the levels of pollutants, generating increases in the concentrations of PM2.5 and PM10. The biochemical results suggested effects mediated by different mechanisms, where PM2.5 induced an increase in antioxidant capacity with activation of the defense system and lipoperoxidation. Results suggest that PM10 reduces the antioxidant capacity and activates the glutathione S-transferase activity enzymatic action, but also induces lipoperoxidation in all groups of animals exposed to samples collected during the dry period of 2016. Individuals exposed to PM2.5 in 2017 wet and dry periods and PM10 in 2016 and 2017 dry periods shown a decrease in size compared to controls, while for fertility data, there was a decrease only in individuals exposed to PM2.5 in the periods that the highest levels of PM concentration. We conclude that despite the positive issues linked to the hosting of mega-events, their infrastructure requirements can compromise air quality and bring damage related to lipoperoxidation and physiological changes in the life cycle of biological systems, such as what happened to C. elegans exposed to tested extracts. Also, rainy events reduced the presence of these pollutants, washing the atmosphere.

Zhao Y et al. (2019) Oxid Med Cell Longev "Fine Particulate Matter Leads to Unfolded Protein Response and Shortened Lifespan by Inducing Oxidative Stress in C. elegans."

Wu H, Chi Y, Zhao Y, Jin L, Yang J, Zhen Q

[

Oxid Med Cell Longev,

2019]

Oxidative stress has been proven as one of the most critical regulatory mechanisms involved in fine Particulate Matter- (PM2.5-) mediated toxicity. For a better understanding of the underlying mechanisms that enable oxidative stress to participate in PM2.5-induced toxic effects, the current study explored the effects of oxidative stress induced by PM2.5 on UPR and lifespan in C. elegans. The results implicated that PM2.5 exposure induced oxidative stress response, enhanced metabolic enzyme activity, activated UPR, and shortened the lifespan of C. elegans. Antioxidant N-acetylcysteine (NAC) could suppress the UPR through reducing the oxidative stress; both the antioxidant NAC and UPR inhibitor 4-phenylbutyric acid (4-PBA) could rescue the lifespan attenuation caused by PM2.5, indicating that the antioxidant and moderate proteostasis contribute to the homeostasis and adaptation to oxidative stress induced by PM2.5.

Yang R et al. (2016) Toxicol Res (Camb) "Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM_2.5) during Spring Festival in Beijing in nematode Caenorhabditis elegans."

Rui Q, Tian P, Wang X, Li G, Wang D, Li Y, Kong L, Tao J, Ma Y, Yang R, Zhang N, Wei J

[

Toxicol Res (Camb),

2016]

In this study, we performed the toxicological assessment of outdoor PM2.5 collected from Beijing during Spring Festival using the in vivo assay system of Caenorhabditis elegans. Acute exposure to outdoor PM2.5 at a concentration of 10 mg L-1 and prolonged exposure to outdoor PM2.5 at concentrations of 0.1-10 mg L-1 decreased locomotion behavior and caused significant induction of intestinal ROS production. Meanwhile, outdoor PM2.5 exposure induced significant expression of gene (mtl-1 and mtl-2) encoded metallothioneins in the intestine. Mutation of the mtl-1 or mtl-2 gene resulted in a susceptible property of nematodes to outdoor PM2.5 toxicity. Genetic assays suggested that mtl-1 and mtl-2 genes acted downstream of the daf-16 gene encoding a FOXO transcriptional factor and daf-2 gene encoding an insulin receptor in the insulin signaling pathway to regulate outdoor PM2.5 toxicity. DAF-2 further acted upstream of DAF-16 and suppressed the function of DAF-16 to regulate outdoor PM2.5 toxicity. Therefore, we identified a signaling cascade of DAF-2-DAF-16-MTL-1/2 in the control of outdoor PM2.5 toxicity in nematodes. Our study provides an important molecular basis for the potential toxicity of outdoor PM2.5 during Spring Festival in Beijing in nematodes. Especially, our study will highlight the potential adverse effects of outdoor PM2.5 during Spring Festival on environmental organisms.

Inokuchi A et al. (2015) J Appl Toxicol "Effects of lithium on growth, maturation, reproduction and gene expression in the nematode Caenorhabditis elegans."

Matsusaki H, Yamamoto R, Takumi S, Morita F, Inokuchi A, Arizono K, Tominaga N, Ishibashi H

[

J Appl Toxicol,

2015]

Lithium (Li) has been widely used to treat bipolar disorder, and industrial use of Li has been increasing; thus, environmental pollution and ecological impacts of Li have become a concern. This study was conducted to clarify the potential biological effects of LiCl and Li(2)CO(3) on a nematode, Caenorhabditis elegans as a model system for evaluating soil contaminated with Li. Exposure of C. elegans to LiCl and Li(2)CO(3) decreased growth/maturation and reproduction. The lowest observed effect concentrations for growth, maturation and reproduction were 1250, 313 and 10 000m, respectively, for LiCl and 750, 750 and 3000m, respectively, for Li(2)CO(3). We also investigated the physiological function of LiCl and LiCO(3) in C. elegans using DNA microarray analysis as an eco-toxicogenomic approach. Among approximately 300 unique genes, including metabolic genes, the exposure to 78m LiCl downregulated the expression of 36 cytochrome P450, 16 ABC transporter, 10 glutathione S-transferase, 16 lipid metabolism and two vitellogenin genes. On the other hand, exposure to 375m Li(2)CO(3) downregulated the expression of 11 cytochrome P450, 13 ABC transporter, 13 lipid metabolism and one vitellogenin genes. No gene was upregulated by LiCl or Li(2)CO(3). These results suggest that LiCl and Li(2)CO(3) potentially affect the biological and physiological function in C. elegans associated with alteration of the gene expression such as metabolic genes. Our data also provide experimental support for the utility of toxicogenomics by integrating gene expression profiling into a toxicological study of an environmentally important organism such as C. elegans.

McColl G et al. (2008) J Biol Chem "Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans."

Melov S, McColl G, Lithgow GJ, Vantipalli MC, Killilea DW, Hubbard AE

[

J Biol Chem,

2008]

Lithium (Li+) has been used to treat mood affect disorders, including bipolar, for decades (1;2). This drug is neuroprotective and has several identified molecular targets. However, it has a narrow therapeutic range and the underlying mechanism(s) of its therapeutic action is not understood. Here we describe a pharmacogenetic study of Li+ in the nematode Caenorhabditis elegans. Exposure to Li+ at clinically relevant concentrations throughout adulthood increases survival during normal aging (up to 46% median increase). Longevity is extended via a novel mechanism with altered expression of genes encoding nucleosome-associated functions. Li+ treatment results in reduced expression of the worm ortholog of LSD-1 (T08D10.2), a histone demethylase; knockdown by RNA interference (RNAi) of T08D10.2 is sufficient to extend longevity (~25% median increase), suggesting Li+ regulates survival by modulating histone methylation and chromatin structure.

Wu Q et al. (2017) Toxicol Res (Camb) "Coal combustion related fine particulate matter (PM_2.5) induces toxicity in Caenorhabditis elegans by dysregulating microRNA expression."

Zhao F, Wang D, Wu Q, Han X

[

Toxicol Res (Camb),

2017]

We employed an in vivo assay system of Caenorhabditis elegans to determine if and which microRNAs (miRNAs) were dysregulated upon exposure to coal combustion related fine particulate matter (PM2.5) by profiling the miRNAs using SOLiD sequencing. From this, expression of 25 miRNAs was discovered to become dysregulated by exposure to PM2.5. Using the corresponding C. elegans deletion mutants, 5 miRNAs (mir-231, mir-232, mir-230, mir-251 and mir-35) were found to be involved in the control of PM2.5 toxicity. Furthermore, mutation of mir-231 or mir-232 induced a resistance to PM2.5 toxicity, whereas mutation of mir-230, mir-251, or mir-35 induced a susceptibility to PM2.5 toxicity. SMK-1, an ortholog of the mammalian SMEK protein, was identified as a molecular target for mir-231 in the regulation of PM2.5 toxicity. In addition, the genes of sod-3, sod-4 and ctl-3, which are necessary for protection against oxidative stress, were determined to be important downstream targets of smk-1 in the regulation of PM2.5 toxicity. The triggering of this mir-231-SMK-1-SOD-3/SOD-4/CTL-3 signaling pathway may be a critical molecular basis for the role of oxidative stress in the induction of coal combustion related PM2.5 toxicity.

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