Eom HJ et al. (2015) Environ Health Toxicol "Effect of aspect ratio on the uptake and toxicity of hydroxylated-multi walled carbon nanotubes in the nematode, Caenorhabditis elegans."

Jeong JS, Choi J, Eom HJ

[Environ Health Toxicol, 2015]

OBJECTIVES: In this study, the effect of tube length and outer diameter (OD) size of hydroxylated-multi walled carbon nanotubes (OH-MWCNTs) on their uptake and toxicity was investigated in the nematode Caenorhabditis elegans using a functional mutant analysis. METHODS: The physicochemical properties of three different OH-MWCNTs were characterized. Uptake and toxicity were subsequently investigated on C. elegans exposed to MWCNTs with different ODs and tube lengths. RESULTS: The results of mutant analysis suggest that ingestion is the main route of MWCNTs uptake. We found that OH-MWCNTs with smaller ODs were more toxic than those with larger ODs, and OH-MWCNTs with shorter tube lengths were more toxic than longer counterparts to C. elegans. CONCLUSIONS: Overall the results suggest the aspect ratio affects the toxicity of MWCNTs in C. elegans. Further thorough study on the relationship between physicochemical properties and toxicity needs to be conducted for more comprehensive understanding of the uptake and toxicity of MWCNTs.

Hwang, Hyeonjeong et al. (2021) International Worm Meeting "Exoribonuclease ERI-1 regulates ascr#3 avoidance behavior in C. elegans"

Jo, Sujin, Oh, Seunghee, Hwang, Hyeonjeong, Kim, Kyuhyung

[International Worm Meeting, 2021]

Small RNAs are short, non-coding RNAs that can regulate gene expression. Recent studies suggested that small RNAs pathway modulates animal behavior (Juang et al., 2013; Posner et al., 2019; Picao-Osorio et al., 2015). However, the mechanisms by which small RNAs regulate animal behavior are not fully understood. C. elegans secretes a complex pheromone mixture called ascarosides. A pheromone component, ascr#3 (asc-deltaC9, C9) has been shown to elicit avoidance behavior in wild-type hermaphrodites (Jang et al., 2012). Here, we investigate the roles of small RNAs in ascr#3-mediated avoidance behavior. First, we screened candidate mutants including rrf-3, ergo-1, drh-3, dcr-1, alg-4; alg-3, and rde-4 of which gene products are known to regulate small RNA pathways. We found that four alleles of eri-1 mutants exhibit defects in ascr#3 avoidance. We then restored the phenotype by expressing eri-1 cDNA under the control of its own promoter and pan-neuronal promoter. Next, we examined expression patterns of eri-1 and found that eri-1 is expressed in a few neurons in the head and tail. We identified that these neurons include either AVJ or AVH in the head and PVP in the tail. Besides, we found a correlation between eri-1 expression level in AVJ/AVH but not in PVP and ascr#3 avoidance; animals showing high eri-1 expression appear to exhibit increased ascr#3 avoidance and vice-versa. Moreover, we found that eri-1 expression levels in AVJ/AVH and ascr#3 avoidance are increased with maternal age. Taken together, these results indicate that exoribonuclease eri-1 regulates ascr#3 avoidance behavior, which provides an opportunity to study the roles of small RNAs in animal behavior.

Yu Y et al. (2020) ACS Chem Biol "Untargeted Approach for Revealing Electrophilic Metabolites."

Maxwell DN, Zhang B, Le HH, Schroeder FC, Wrobel CJJ, Yu Y, Curtis BJ, Pan JY

[ACS Chem Biol, 2020]

Reactive electrophilic intermediates such as coenzyme A esters play central roles in metabolism but are difficult to detect with conventional strategies. Here, we introduce hydroxylamine-based stable isotope labeling to convert reactive electrophilic intermediates into stable derivatives that are easily detectable <i>via</i> LC-MS. In the model system <i>Caenorhabditis elegans</i>, parallel treatment with ¹⁴NH₂OH and ¹⁵NH₂OH revealed &gt;1000 labeled metabolites, e.g., derived from peptide, fatty acid, and ascaroside pheromone biosyntheses. Results from NH₂OH treatment of a pheromone biosynthesis mutant, <i>acox-1.1</i>, suggested upregulation of thioesterase activity, which was confirmed by gene expression analysis. The upregulated thioesterase contributes to the biosynthesis of a specific subset of ascarosides, determining the balance of dispersal and attractive signals. These results demonstrate the utility of NH₂OH labeling for investigating complex biosynthetic networks. Initial results with <i>Aspergillus</i> and human cell lines indicate applicability toward uncovering reactive metabolomes in diverse living systems.

Zhang W et al. (2011) Nanoscale "Biosafety assessment of Gd@C82(OH)22 nanoparticles on Caenorhabditis elegans."

Zhao B, Zhang W, Zhang L, Sun B, Zhao Y, Nie G

[Nanoscale, 2011]

Gd@C(82)(OH)(22), a water-soluble endohedral metallofullerene derivative, has been proven to possess significant antineoplastic activity in mice. Toxicity studies of the nanoparticle have shown some evidence of low or non toxicity in mice and cell models. Here we employed Caenorhabditis elegans (C. elegans) as a model organism to further evaluate the short- and long-term toxicity of Gd@C(82)(OH)(22) and possible behavior changes under normal and stress culture conditions. With treatment of Gd@C(82)(OH)(22) at 0.01, 0.1, 1.0 and 10 g ml(-1) within one generation (short-term), C. elegans showed no significant decrease in longevity or thermotolerance compared to the controls. Furthermore, when Gd@C(82)(OH)(22) treatment was extended up to six generations (long-term), non-toxic effects to the nematodes were found. In addition, data from body length measurement, feeding rate and egg-laying assays with short-term treatment demonstrated that the nanoparticles have no significant impact on the individual growth, feeding behavior and reproductive ability, respectively. In summary, this work has shown that Gd@C(82)(OH)(22) is tolerated well by worms and it has no apparent toxic effects on longevity, stress resistance, growth and behaviors that were observed in both adult and young worms. Our work lays the foundations for further developments of this anti-neoplastic agent for clinical applications.

Liu X et al. (2020) RSC Adv "A naphthalimide-based turn-on fluorescence probe for peroxynitrite detection and imaging in living cells."

Zhou X, Liu X, Cui L, Guo T, Zhang S, Gu F, Zhou W

[RSC Adv, 2020]

Peroxynitrite (ONOO^-) is a potent biological oxidant that plays a significant role in diverse physiological and pathological processes. A novel fluorescent probe HCA-OH was developed for specific and sensitive detection of peroxynitrite, and displayed a significant fluorescence turn-on signal. With low cytotoxicity and good photostability, the probe HCA-OH could be applied in imaging ONOO^- distribution in HepG2 cells and live C. elegans in real time. Therefore, the probe can be a promising tool for imaging in vivo.

Choi, Shin S. et al. (2011) International Worm Meeting "Apoptosis-mediated toxicity of water stable carbon nanoparticles in Caenorhabditis elegans ."

Choi, Shin S., Cha, Yoon J.

[International Worm Meeting, 2011]

The application of nanoparticles in various fields has been evolved rapidly due to its authentic physicochemical properties. The potential biological or environmental toxicity of nanoparticles, however, has been frequently reported using in vitro systems. In this study, the toxicity of fullerene (nC60) and fullerol (C60-OH) in Caenorhabditis elegans was assessed through the measurement of lifespan, body size, and brood size. The water-stable colloids form of nC60 are prepared through the long-term exposure of fullerene, C60 in THF. We confirmed that the oral-administrated carbon nanoparticles were accumulated in the animals for several days after feeding the mixture of bacterial food and nC60 or C60-OH to the L4 larvas of C. elegans. The C60-OH reduced the viability of animals while no decrease in survival was found in the animals fed with nC60. We have also found that both nC60 and C60-OH reduced the reproduction of C. elegans. In order to illuminate the genetic mechanism of toxicity induced by those nanoparticles, the assessment of viability and fertility was carried out using the strains mutated in oxidative stress or programmed cell death regulators.

Margier M et al. (2018) FASEB J "ABCB1 (P-glycoprotein) regulates vitamin D absorption and contributes to its transintestinal efflux."

Borel P, Lebrun C, Desmarchelier C, Bluteau A, Reboul E, Lespine A, le May C, Margier M, Collet X, Defoort C, Andre F

[FASEB J, 2018]

Efficient intestinal absorption of dietary vitamin D is required in most people to ensure an adequate status. Thus, we investigated the involvement of ATP binding cassette subfamily B member 1 (ABCB1) in vitamin D intestinal efflux. Both cholecalciferol (D₃) and 25-hydroxycholecalciferol [25(OH)D₃] apical effluxes were decreased by chemical inhibition of ABCB1 in Caco-2 cells and increased by ABCB1 overexpression in Griptites or Madin-Darby canine kidney type II cells. Mice deficient for the 2 murine ABCB1s encoded by Abcb1a and Abcb1b genes ( Abcb1^-/-) displayed an accumulation of 25(OH)D₃ in plasma, intestine, brain, liver, and kidneys, together with an increased D₃ postprandial response after gavage compared with controls. 25(OH)D₃ efflux through Abcb1^-/- intestinal explants was markedly decreased compared with controls. This reduction of 25(OH)D₃ transfer from plasma to lumen was further confirmed in vivo in intestine-perfused mice. Docking experiments established that both D₃ and 25(OH)D₃ could bind with high affinity to Caenorhabditis elegans P-glycoprotein, used as an ABCB1 model. Finally, in a group of 39 healthy male adults, a single-nucleotide polymorphism (SNP) in ABCB1 (rs17064) was significantly associated with the fasting plasma 25(OH)D₃ concentration. Thus, we showed here for the first time that ABCB1 is involved in neo-absorbed vitamin D efflux by the enterocytes and that it also contributes to vitamin D transintestinal excretion and likely impacts vitamin D status.-Margier, M., Collet, X., le May, C., Desmarchelier, C., Andre, F., Lebrun, C., Defoort, C., Bluteau, A., Borel, P., Lespine, A., Reboul, E. ABCB1 (P-glycoprotein) regulates vitamin D absorption and contributes to its transintestinal efflux.

Maine EM et al. (1994) Worm Breeder's Gazette "Mutations That Enhance glp-1 Identify Genes Required For Various Aspects of Germline Development."

Gelber MB, Smardon AM, Shu P, Qiao L, Maine EM, Lissemore JL

[Worm Breeder's Gazette, 1994]

Mutations that enhance glp-1 identify genes required for various aspects of germline development. Eleanor Maine, Li Qiao, Jim Lissemore-, Pei Shu, Anne Smardon, and Melanie Gelber. Biology Dept., Syracuse University, Syracuse, NY 13244 and Biology Dept., John Carroll University, Cleveland, OH 44118.

Takashi Murayama et al. (2006) East Asia C. elegans Meeting "Chemotactic response toward basic pH in C. elegans"

Ichiro Maruyama, Takashi Murayama

[East Asia C. elegans Meeting, 2006]

C. elegans responds to water-soluble chemicals such as ions and amino acids. We are especially interested in the response to OH^- as basic pH. In C. elegans, acid pH (H⁺) is sensed as a nociceptive stimuli, and basic pH (OH^-) is sensed as an attractive stimuli (Ward, 1973; Dusenbery, 1974). Sambongi et al. (2000) have shown some of amphid chemosensory neurons are responsible for acid pH avoidance by ablating these neurons. In general, however, a neural mechanism underlying OH^- response in any animals still remains to be explored. To investigate the OH^- chemosensation, we have developed an assay system. On the assay plate with a pH gradient from pH 7.0 to pH 10.0, wild-type animals move toward basic pH along the gradient. When some chemotaxis mutants were analyzed with this assay, osm-6, a sensory cilium-defective mutant, did not show any response to basic pH. In addition, some chemotaxis mutants have normal sensory cilia are found to be insensitive to the pH gradient. Now, we are analyzing some other chemotaxis mutants, and trying to isolate mutants showing irregular response to basic pH. Ward (1973), PNAS 70, 817. Dusenbery (1974), J. Exp. Zool. 188, 41. Sambongi et al. (2000), Neuroreport 11, 2229.

Li, Yuanbao et al. (2015) International Worm Meeting "Fatty acid two-hydroxylase (FATH-1) selectively regulates apical membrane trafficking in the C. elegans intestinal cells."

Zheng, Hanxi, Fu, Rong, Li, Yuanbao, Su, Xiong, Zhang, Huimin

[International Worm Meeting, 2015]

The hydroxylation of fatty acids (FA) at the C-2 position is the first step of FA a-oxidation and generates 2-hydroxy sphingolipids. However, the precise roles of FA 2-hydroxylation in whole cell homeostasis remains unclear. Fatty acid 2-hydroxylase (FA2H) is an enzyme that catalyzes the 2-hydroxylation of FAs to produce 2-hydroxy FAs (2-OH FAs). Here we use C. elegans intestine as the model and investigate the function of fath-1/C25A1.5, the worm homolog for mammalian FA2H enzyme, in protein transport and metabolism. GFP translational fusion reporter showed that C. elegans FATH-1 is expressed in most developmental stages and in most tissues. Loss of fath-1 expression results in severe growth retardation and shortened lifespan. Exogenous 2-OH FA rescue experiment revealed that FATH-1 primarily functions through its catalytic product (R)-2-OH FA. Tissue-specific RNAi knockdown showed that FATH-1 function is mainly required in the digestive tract but not in the epidermis. At the subcellular level, we found that loss of fath-1 expression induces endoplasmic reticulum stress and inhibits lipid droplets formation. Further analysis showed that loss of fath-1 selectively disrupts apical endosome recycling, but not early endocytosis or basal endosome recycling. By using the "click-chemistry" labeling method, we showed that 2-OH FA and derivatives are mainly enriched in vesicles close to the apical membrane of the intestinal cells and partially co-localize with apical recycling endosomes. Taken together, we propose that the (R)-2-OH FA produced by FATH-1 selectively marks apical endocytic vesicles to regulate protein transport and metabolism, therefore helps maintaining the cellular homeostasis.