Brena D et al. (2020) Sci Rep "Ancestral function of Inhibitors-of-kappaB regulates Caenorhabditis elegans development."

Marruecos L, Cornes E, Garcia-Lopez A, Brena D, Bigas A, Fernandez L, Espinosa L, Kukhtar D, Islam ABMMK, Guillen Y, Porta-De-La-Riva M, Bertran J, Ceron J, Campos-Vicens L, Pecharroman I

[Sci Rep, 2020]

Mammalian IB proteins (IBs) exert their main function as negative regulators of NF-B, a central signaling pathway controlling immunity and inflammation. An alternative chromatin role for IBs has been shown to affect stemness and cell differentiation. However, the involvement of NF-B in this function has not been excluded. NFKI-1 and IKB-1 are IB homologs in Caenorhabditis elegans, which lacks NF-B nuclear effectors. We found that nfki-1 and ikb-1 mutants display developmental defects that phenocopy mutations in Polycomb and UTX-1 histone demethylase, suggesting a role for C. elegans IBs in chromatin regulation. Further supporting this possibility (1) we detected NFKI-1 in the nucleus of cells; (2) NFKI-1 and IKB-1 bind to histones and Polycomb proteins, (3) and associate with chromatin in vivo, and (4) mutations in nfki-1 and ikb-1 alter chromatin marks. Based on these results, we propose that ancestral IB inhibitors modulate Polycomb activity at specific gene subsets with an impact on development.

Cornejo Castro EM et al. (2010) J Neural Transm "Parkinson's disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans."

Autenrieth IB, Fiesel FC, Cornejo Castro EM, Schutz M, Oberhettinger P, Springer W, Kahle PJ, Waak J, Weber SS

[J Neural Transm, 2010]

DJ-1 is a neuroprotective gene mutated in recessive Parkinson's disease (PD). In addition to direct protective functions in neurons, DJ-1 regulates neuroinflammatory signaling in primary mouse brain astrocytes. To assess the influence of DJ-1 on innate immunity signaling in vivo, we have generated djr-1 knockout Caenorhabditis elegans. When grown on pathogenic gram-negative bacteria, djr-1 (-/-) worms showed stronger phosphorylation of p38 mitogen-activated protein kinase (PMK-1) and hyper-induction of PMK-1 target genes. Thus, PD-associated DJ-1 contributes to regulation of innate immunity.

Johnson CD et al. (1983) J Neurochem "Multiple molecular forms of acetylcholinesterase in the nematode Caenorhabditis elegans."

Johnson CD, Russell RL

[J Neurochem, 1983]

Extracts of the nematode Caenorhabditis elegans contain five molecular forms of acetylcholinesterase (AChE) activity that can be separated by a combination of selective solubilization, velocity sedimentation, and ion-exchange chromatography. These are called form IA (5.2s), form IB (4.9s), form II (6.7s), form III (11.3s), and form IV (13.0s). All except form III are present in significant amounts in rapidly prepared extracts and are probably native; form III is probably derived autolytically from form IV. Most of forms IA and IB can be solubilized by repeated extractions without detergent, whereas forms II, III, and IV require detergent for effective solubilization and may therefore be membrane-bound. High salt concentrations are not required for, and do not aid in, the solubilization of these forms. For all forms, molecular weights and frictional ratios have been estimated by a combination of gel permeation chromatography and velocity sedimentations in both H2O and D2O. The molecular weight estimates range from 83,000 to 357,000 and only form II shows extensive asymmetry. The separated forms have been characterized with respect to substrate affinity, substrate specificity, inhibitor sensitivity, thermal inactivation, and detergent sensitivity. Judging by these properties, C. elegans is like other invertebrates in that none of its cholinesterase forms resembles either the "true" or the "pseudo" cholinesterase of vertebrates. However, internal comparison of the C. elegans forms clearly distinguishes forms IA, III, and IV as a group from forms IB and II; the former are therefore designated "class A" forms, the latter "class B" forms. Genetic evidence indicates that separate genes control class A and class B forms, and that these two classes overlap functionally. Several factors, including kinetic properties, molecular asymmetry, molecular size, and solubility, all suggest that a molecular model of the multiple cholinesterase forms observed in vertebrate electric organs probably does not apply in C. elegans. Potential functional roles and subunit structures of the multiple AChE forms within each C. elegans class are

Martin C et al. (2021) Chemosphere "Bioassays to assess the ecotoxicological impact of polyethylene microplastics and two organic pollutants, simazine and ibuprofen."

Mengs G, Nande M, San Andres MD, Fajardo C, Martin C, Sanchez-Fortun S, Gonzalez F, Martin M, Costa G

[Chemosphere, 2021]

Research on the environmental impact of plastics, especially on the effect of microplastics (MPs), has become a priority issue in recent years, mainly in terrestrial ecosystems where there is a lack of studies. This work aims to assess the impact of two types of polyethylene MPs, white microbeads (W) and fluorescent blue microbeads (FB), and their interactions with two contaminants, ibuprofen (Ib) and simazine (Sz), on different organisms. A set of bioassays for Vibrio fischeri, Caenorhabditis elegans and Lactuca sativa was carried out, which helped to establish the ecotoxicological impact of those pollutants. C.elegans showed the least sensitivity, while V.fischeri and L.sativa showed a high toxicological response to MPs alone. We found that W and FB induced an inhibition of 27% and 5.79%, respectively, in V.fischeri, and the growth inhibition rates were near 70% in L.sativa for both MPs. MPs exhibited a potential role as contaminant vectors in V.fischeri since the inhibition caused by W-Ib or W-Sz complexes was near 39%. The W-Sz complex significantly reduced leaf development in L.sativa, and a reduction of 30% in seed germination was detected when the complex FB-Sz was tested. This study reveals the importance of designing a complete set of analyses with organisms from different trophic levels, considering the great variability in the effects of MPs and the high number of relevant factors.

Sun S et al. (2019) Biosci Microbiota Food Health "Toll-like receptor homolog TOL-1 regulates Bifidobacterium infantis-elicited longevity and behavior in Caenorhabditis elegans."

Komura T, Nishikawa Y, Mizuno Y, Kage-Nakadai E, Sun S

[Biosci Microbiota Food Health, 2019]

<i>Bifidobacterium infantis</i>, a Gram-positive bacterium, is one of the commonly used probiotics. We previously showed that <i>B. infantis</i> modified host defense systems and extended the lifespan of the nematode <i>Caenorhabditis elegans</i>. In the present study, we showed that the lifespan extension caused by <i>B. infantis</i> was enhanced in animals having a mutation in the <i>tol-1</i> gene that encodes the sole <i>C. elegans</i> homolog of Toll-like receptors (TLRs). Meanwhile, lifespan increased by other probiotic bacteria, such as <i>Bacillus subtilis</i> or <i>Clostridium butyricum</i>, was not affected in the <i>tol-1</i> mutant animals. A microarray analysis revealed that the expression of innate immune response-related genes was significantly increased in the <i>tol-1</i> mutant. Worms with the <i>tol-1</i> mutation exhibited reduced leaving behavior from the <i>B. infantis</i> lawn, while canonical downstream factors <i>trf-1</i>/TRAF and <i>ikb-1</i>/IB appeared to not be involved. In conclusion, <i>C. elegans tol-1</i>/TLR regulates <i>B. infantis</i>-induced longevity and also regulates behavior against <i>B. infantis</i>.

Hunt MC et al. (1999) J Biol Chem "Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise a highly conserved novel multi-gene family involved in lipid metabolism."

Huttunen MK, Alexson SE, Svensson LT, Orii KE, Nousiainen SE, Hunt MC

[J Biol Chem, 1999]

Long chain acyl-CoA esters are important intermediates in degradation and synthesis of fatty acids, as well as having important functions in regulation of intermediary metabolism and gene expression. Although the physiological functions for most acyl-CoA thioesterases have not yet been elucidated, previous data suggest that these enzymes may be involved in lipid metabolism by modulation of cellular concentrations of acyl-CoAs and fatty acids. In line with this, we have cloned four highly homologous acyl-CoA thioesterase genes from mouse, showing multiple compartmental localizations. The nomenclature for these genes has tentatively been assigned as CTE-I (cytosolic), MTE-I (mitochondrial), and PTE-Ia and Ib (peroxisomal), based on the identification of putative targeting signals. Although the various isoenzymes show between 67% and 94% identity at amino acid level, each individual enzyme shows a specific tissue expression. Our data suggest that all four genes are located within a very narrow cluster on chromosome 12 in mouse, similar to a sequence cluster on human chromosome 14, which identified four genes homologous to the mouse thioesterase genes. Four related genes were also identified in Caenorhabditis elegans, all containing putative PTS1 targeting signals, suggesting that the ancestral type I thioesterase gene(s) is/are of peroxisomal origin. All four thioesterases are differentially expressed in tissues examined, but all are inducible at mRNA level by treatment with the peroxisome proliferator clofibrate, or during the physiological condition of fasting, both of which conditions cause a perturbation in overall lipid homeostasis. These results strongly support the existence of a novel multi-gene family cluster of mouse acyl-CoA thioesterases, each with a distinct function in lipid metabolism.

Park JH et al. (2014) Aging Cell "Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice."

Jung M, Chung HY, Ha H, Park JH, Kim M, Lee JH

[Aging Cell, 2014]

The liver is one of the most susceptible organs to aging, and hepatic inflammation and fibrosis increase with age. Chronic inflammation has been proposed as the major molecular mechanism underlying aging and age-related diseases, whereas calorie restriction has been shown to be the most effective in extending mammalian lifespan and to have anti-aging effects through its anti-inflammatory action. Thus, it is necessary to develop effective calorie restriction mimetics. Daumone [(2)-(6R)-(3,5-dihydroxy-6-methyltetrahydropyran-2-yloxy)heptanoic acid], a pheromone secreted by Caenorhabditis elegans, forces them to enter the dauer stage when facing inadequate conditions. Because Caenorhabditis elegans live longer during the dauer stage under energy deprivation, it was hypothesized that daumone may improve survival in mammals by mimicking calorie restriction. Daumone (2mg kg(-1) day(-1) ) was administered orally for 5months to 24-month-old male C57BL/6J mice. Daumone was found to reduce the risk of death by 48% compared with age-matched control mice, and the increased plasma insulin normally presented in old mice was significantly reduced by daumone. The increased hepatic hypertrophy, senescence-associated -galactosidase activity, insulin resistance, lipid accumulation, inflammation, oxidative stress, and fibrosis in old mice were significantly attenuated by daumone. From a mechanistic view, daumone reduced the phosphorylation of the IB and upregulation of Rela and Nfkbia mRNA in the livers of old mice. The anti-inflammatory effect of daumone was confirmed in lipopolysaccharide-induced liver injury model. Oral administration of daumone improves survival in mice and delivers anti-aging effects to the aged liver by modulating chronic inflammation, indicating that daumone could be developed as an anti-aging compound.

Fajardo C et al. (2021) Chemosphere "Assessing the role of polyethylene microplastics as a vector for organic pollutants in soil: Ecotoxicological and molecular approaches."

Rodriguez C, de Lucas Burneo JJ, Martin C, Sanchez-Fortun S, Martin M, Nande M, Costa G, Fajardo C, Mengs G

[Chemosphere, 2021]

Microplastics (MPs), pharmaceuticals and pesticides are emerging pollutants with proposed negative impacts on the environment. Rising interest in investigations of MPs is likely related to their potential to accumulate in agricultural systems as the base of the food chain. We applied an integrated approach using classic bioassays and molecular methods to evaluate the impact associated with a mixture of three types of polyethylene (PE) microbeads, namely, white (W), blue (B), and fluorescent blue (FB), and their interactions with pollutants (OCs), including ibuprofen (IB), sertraline (STR), amoxicillin (AMX) and simazine (SZ), on different soil organisms. PE-MPs exhibited different abilities for the adsorption of each OC; W selectively adsorbed higher amounts of SZ, whereas B and FB preferably retained AMX. Standard soil was artificially contaminated with OCs and MPs (alone or combined with OCs) and incubated for 30 days. The presence of MPs or MPs and OCs (MIX) in soil did not produce any effect on Caenorhabditis elegans endpoint growth, reproduction, or survival. Inhibition of leaf growth in Zea mays was detected, but this negative effect declined over time, while the inhibition of root growth increased, especially when OCs (32%) or MIX (47%) were added. Moreover, the expression of the antioxidant genes CAT 1, SOD-1A and GST 1 on plants was affected by the treatments studied. The addition of MPs or MIX significantly affected the soil bacterial phylogenetic profile, which selectively enriched members of the bacterial community (particularly Proteobacteria). The predicted functional profiles of MP/MIX samples indicated a potential impact on the carbon and nitrogen cycle within the soil environment. Our results indicate that MPs and their capability to act as pollutant carriers affect soil biota; further studies should be carried out on the bioavailability of OCs adsorbed by microplastics and how long it takes to leach these OCs into different organisms and/or ecosystems.

Hirabayashi J et al. (2001) Proteomics "Glycome project: concept, strategy and preliminary application to Caenorhabditis elegans."

Arata Y, Kasai K, Hirabayashi J

[Proteomics, 2001]

Glycans play a central role as potential mediators between complex cell societies, because all living organisms consist of cells covered with diverse carbohydrate chains reflecting various cell types and states. However, we have no idea how diverse these carbohydrate chains actually are. The main purpose of this article is to persuade life scientists to realize the fundamental importance of taking some action by becoming involved in "glycomics". "Glycome" is a term meaning the whole set of glycans produced by individual organisms, as the third bioinformative macromolecules to be elucidated next to the genome and proteome. Here a basic strategy is presented. The essence of the project includes the following. (af glycopeptides, but not glycans released from their core proteins, are targeted for linkage to genome databases; Ib) Caenorhabditis elegans is used as the first model organism for this project, since its genome project has already been completed; (c) four essential attributes are adopted to characterize each glycopeptide: (i) cosmid identification number (ID), (ii) molecular weight (M-r), (iii) retention (Rs) of pyridylaminated (PA) oligosacharides in 2-D mapping, and (iv) dissociation constants (K-d's) of PA-oligosaccharides for a set of lectins. Thus, the obtained ID, M-r, R and K-d's construct the glycome database, which will be open as the previous genome and proteome databases. For the project to proceed the "glyco-catch" method is proposed, where a group of target glycopeptides are captured by means of lectin-affinity chromatography after protease digestion. Already glycopeptides from asialofetuin and ovalbumin were successfully captured by galectin-agarose and Con A-agarose, respectively. Further, to examine the practical validity of the method, we extracted membrane proteins from C. elegans with 1% Triton X-100, and isolated specific glycopeptides by use of the same galectin column. One of the glycopeptides was successfully identified in the C. elegans genome database. Finally, for determination of K-d between glycopeptides and lectins, a recently reinforced frontal affinity chromatography (FAC) is proposed as an alternative to define glycan structures in place of determining every covalent structure.