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Elegans apoptosis

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https://www.readbyqxmd.com/read/27885333/astragalus-polysaccharide-suppresses-6-hydroxydopamine-induced-neurotoxicity-in-caenorhabditis-elegans
#1
Haifeng Li, Ruona Shi, Fei Ding, Hongyu Wang, Wenjing Han, Fangli Ma, Minghua Hu, Chung Wah Ma, Zebo Huang
Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27836269/a-novel-method-for-assessing-the-toxicity-of-silver-nanoparticles-in-caenorhabditis-elegans
#2
Xun Luo, Shengmin Xu, Yaning Yang, Yajun Zhang, Shunchang Wang, Shaopeng Chen, An Xu, Lijun Wu
At present, nanotechnology has been producing nanoscale materials with unprecedented speed. Nanomaterials could be inevitably released into the environment owing to their widespread use, and their potential toxicity has caused a great concern. With regard to assessment of nanomaterial toxicity, many studies probably don't truly reflect their toxicity, because the nanoparticles were not stable and uniformly dispersed in the medium. In the present study, the semi-fluid nematode growth gelrite medium (NGG) was used to achieve better distribution of silver nanoparticles (AgNPs)...
November 8, 2016: Chemosphere
https://www.readbyqxmd.com/read/27798844/post-transcriptional-control-of-executioner-caspases-by-rna-binding-proteins
#3
Deni Subasic, Thomas Stoeger, Seline Eisenring, Ana M Matia-González, Jochen Imig, Xue Zheng, Lei Xiong, Pascal Gisler, Ralf Eberhard, René Holtackers, André P Gerber, Lucas Pelkmans, Michael O Hengartner
Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3' untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level...
October 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27794564/human-exceptional-longevity-transcriptome-from-centenarians-is-distinct-from-septuagenarians-and-reveals-a-role-of-bcl-xl-in-successful-aging
#4
Consuelo Borras, Kheira M Abdelaziz, Juan Gambini, Eva Serna, Marta Inglés, Monica de la Fuente, Idoia Garcia, Ander Matheu, Paula Sanchís, Angel Belenguer, Alessandra Errigo, Juan-Antonio Avellana, Ana Barettino, Carla Lloret-Fernández, Nuria Flames, Gianni Pes, Leocadio Rodriguez-Mañas, Jose Viña
Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl - xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging...
October 28, 2016: Aging
https://www.readbyqxmd.com/read/27793714/nf-y-in-invertebrates
#5
REVIEW
Masamitsu Yamaguchi, Md Saheb Ali, Yasuhide Yoshioka, Luong Linh Ly, Hideki Yoshida
Both Drosophila melanogaster and Caenorhabditis elegans (C. elegans) are useful model organisms to study in vivo roles of NF-Y during development. Drosophila NF-Y (dNF-Y) consists of three subunits dNF-YA, dNF-YB and dNF-YC. In some tissues, dNF-YC-related protein Mes4 may replace dNF-YC in dNF-Y complex. Studies with eye imaginal disc-specific dNF-Y-knockdown flies revealed that dNF-Y positively regulates the sevenless gene encoding a receptor tyrosine kinase, a component of the ERK pathway and negatively regulates the Sensless gene encoding a transcription factor to ensure proper development of R7 photoreceptor cells together with proper R7 axon targeting...
October 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27786254/a-novel-approach-using-c-elegans-dna-damage-induced-apoptosis-to-characterize-the-dynamics-of-uptake-transporters-for-therapeutic-drug-discoveries
#6
Arturo Papaluca, Dindial Ramotar
Organic cation transporter (OCT) function is critical for cellular homeostasis. C. elegans lacking OCT-1 displays a shortened lifespan and increased susceptibility to oxidative stress. We show that these phenotypes can be rescued by downregulating the OCT-1 paralogue, OCT-2. Herein, we delineate a biochemical pathway in C. elegans where uptake of genotoxic chemotherapeutics such as doxorubicin and cisplatin, and subsequent DNA damage-induced apoptosis of germ cells, are dependent exclusively upon OCT-2. We characterized OCT-2 as the main uptake transporter for doxorubicin, as well as a number of other therapeutic agents and chemical compounds, some identified through ligand-protein docking analyses...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27766444/flunarizine-rescues-reduced-lifespan-in-cln3-triple-knock-out-caenorhabditis-elegans-model-of-batten-disease
#7
Young Joon Kwon, Marni J Falk, Michael J Bennett
CLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric-onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis of CLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of CLN3 deficiency suggested that FDA-approved calcium channel antagonists may have therapeutic value...
October 20, 2016: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27738134/crystal-structure-of-endonuclease-g-in-complex-with-dna-reveals-how-it-nonspecifically-degrades-dna-as-a-homodimer
#8
Jason L J Lin, Chyuan-Chuan Wu, Wei-Zen Yang, Hanna S Yuan
Endonuclease G (EndoG) is an evolutionarily conserved mitochondrial protein in eukaryotes that digests nucleus chromosomal DNA during apoptosis and paternal mitochondrial DNA during embryogenesis. Under oxidative stress, homodimeric EndoG becomes oxidized and converts to monomers with diminished nuclease activity. However, it remains unclear why EndoG has to function as a homodimer in DNA degradation. Here, we report the crystal structure of the Caenorhabditis elegans EndoG homologue, CPS-6, in complex with single-stranded DNA at a resolution of 2...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27723735/regulation-of-ced-3-caspase-localization-and-activation-by-c-elegans-nuclear-membrane-protein-npp-14
#9
Xudong Chen, Yue Wang, Yu-Zen Chen, Brian L Harry, Akihisa Nakagawa, Eui-Seung Lee, Hongyan Guo, Ding Xue
Caspases are cysteine proteases with critical roles in apoptosis. The Caenorhabditis elegans caspase CED-3 is activated by autocatalytic cleavage, a process enhanced by CED-4. Here we report that the CED-3 zymogen localizes to the perinuclear region in C. elegans germ cells and that CED-3 autocatalytic cleavage is held in check by C. elegans nuclei and activated by CED-4. The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro...
October 10, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27716809/a-high-throughput-small-molecule-screen-for-c-elegans-linker-cell-death-inhibitors
#10
Andrew R Schwendeman, Shai Shaham
Programmed cell death is a ubiquitous process in metazoan development. Apoptosis, one cell death form, has been studied extensively. However, mutations inactivating key mammalian apoptosis regulators do not block most developmental cell culling, suggesting that other cell death pathways are likely important. Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic cell death form mediating the demise of the male-specific linker cell. This cell death process (LCD, linker cell-type death) is morphologically conserved, and its molecular effectors also mediate axon degeneration in mammals and Drosophila...
2016: PloS One
https://www.readbyqxmd.com/read/27706063/a-potential-mechanism-for-the-anti-apoptotic-property-of-koumine-involving-mitochondrial-pathway-in-lps-mediated-raw-264-7-macrophages
#11
Zhi-Hang Yuan, Zeng-Enni Liang, Jing Wu, Jin-E Yi, Xiao-Jun Chen, Zhi-Liang Sun
Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans). Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent. In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated RAW 264.7 cell apoptosis was evaluated. MTT assays showed that koumine obviously increased cell viability in LPS-mediated RAW 264.7 macrophages. Preincubation with koumine ameliorated LPS-medicated apoptosis by decreasing reactive oxygen species (ROS) production, which resulted in a significant decrease in the levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS)...
September 30, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27704811/vobasinyl-iboga-alkaloids-from-tabernaemontana-elegans-cell-cycle-arrest-and-apoptosis-inducing-activity-in-hct116-colon-cancer-cells
#12
Angela Paterna, Sofia E Gomes, Pedro M Borralho, Silva Mulhovo, Cecília M P Rodrigues, Maria-José U Ferreira
Phytochemical investigation of the roots of the African medicinal plant Tabernaemontana elegans led to the isolation of three new (1-3) and two known (4 and 5) bisindole alkaloids of the vobasinyl-iboga type. The structures of 1-3 were assigned by spectroscopic methods, mainly using 1D and 2D NMR experiments. All of the isolated compounds were evaluated for their cytotoxicity against HCT116 colon and HepG2 liver carcinoma cells by the MTS metabolism assay. Compounds 1-3 and 5 were found to be cytotoxic to HCT116 colon cancer cells, displaying IC50 values in the range 8...
October 5, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27698420/pore-architecture-of-tric-channels-and-insights-into-their-gating-mechanism
#13
Hanting Yang, Miaohui Hu, Jianli Guo, Xiaomin Ou, Tanxi Cai, Zhenfeng Liu
Intracellular Ca(2+) signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca(2+) from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca(2+) through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen...
October 3, 2016: Nature
https://www.readbyqxmd.com/read/27669035/e4-ligase-specific-ubiquitination-hubs-coordinate-dna-double-strand-break-repair-and-apoptosis
#14
Leena Ackermann, Michael Schell, Wojciech Pokrzywa, Éva Kevei, Anton Gartner, Björn Schumacher, Thorsten Hoppe
Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27668659/histone-h3k9-methylation-is-dispensable-for-caenorhabditis-elegans-development-but-suppresses-rna-dna-hybrid-associated-repeat-instability
#15
Peter Zeller, Jan Padeken, Robin van Schendel, Veronique Kalck, Marcel Tijsterman, Susan M Gasser
Histone H3 lysine 9 (H3K9) methylation is a conserved modification that generally represses transcription. In Caenorhabditis elegans it is enriched on silent tissue-specific genes and repetitive elements. In met-2 set-25 double mutants, which lack all H3K9 methylation (H3K9me), embryos differentiate normally, although mutant adults are sterile owing to extensive DNA-damage-driven apoptosis in the germ line. Transposons and simple repeats are derepressed in both germline and somatic tissues. This unprogrammed transcription correlates with increased rates of repeat-specific insertions and deletions, copy number variation, R loops and enhanced sensitivity to replication stress...
September 26, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27650246/somatically-expressed-germ-granule-components-pgl-1-and-pgl-3-repress-programmed-cell-death-in-c-elegans
#16
Mohammad Al-Amin, Hyemin Min, Yhong-Hee Shim, Ichiro Kawasaki
We previously reported that germline apoptosis in C. elegans increased by loss of PGL-1 and PGL-3, members of a family of constitutive germ-granule components, from germ cells in adult hermaphrodite gonads. In this study, we found that somatic apoptosis was reduced in synthetic multivulva class B (synMuv B) mutants due to ectopic expression of PGL-1 and PGL-3 in the soma. In synMuv B-mutant somatic cells, CED-4 expression level was reduced due to ectopic expression of PGL-1. Furthermore, in contrast to wild type, somatic apoptosis in synMuv B mutants increased following DNA damage in a SIR-2...
September 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27619188/structural-and-functional-characterisation-of-foxo-acan-daf-16-from-the-parasitic-nematode-angiostrongylus-cantonensis
#17
Baolong Yan, Weiwei Sun, Lanzhu Yan, Liangliang Zhang, Yuan Zheng, Yuzhen Zeng, Huicong Huang, Shaohui Liang
Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C...
September 9, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27616029/-3-r-hydroxytabernaelegantine-c-a-bisindole-alkaloid-with-potent-apoptosis-inducing-activity-in-colon-hct116-sw620-and-liver-hepg2-cancer-cells
#18
Angela Paterna, Sofia E Gomes, Pedro M Borralho, Silva Mulhovo, Cecília M P Rodrigues, Maria-José U Ferreira
ETHNOPHARMACOLOGICAL RELEVANCE: Tabernaemontana elegans Stapf. (Apocynaceae) is a medicinal plant traditionally used in African countries to treat cancer. AIMS OF THE STUDY: To discover new apoptosis inducing lead compounds from T. elegans and provide scientific validation of the ethnopharmacological use of this plant. MATERIALS AND METHODS: Through fractionation, (3'R)-hydroxytaberanelegantine C (1), a vobasinyl-iboga bisindole alkaloid, was isolated from a cytotoxic alkaloid fraction of the methanol extract of T...
September 8, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27605049/synaptonemal-complex-components-are-required-for-meiotic-checkpoint-function-in-caenorhabditis-elegans
#19
Tisha Bohr, Guinevere Ashley, Evan Eggleston, Kyra Firestone, Needhi Bhalla
Synapsis involves the assembly of a proteinaceous structure, the synaptonemal complex (SC), between paired homologous chromosomes and is essential for proper meiotic chromosome segregation. In C. elegans, the synapsis checkpoint selectively removes nuclei with unsynapsed chromosomes by inducing apoptosis. This checkpoint depends on Pairing Centers (PCs), cis- acting sites that promote pairing and synapsis. We have hypothesized that the stability of homolog pairing at PCs is monitored by this checkpoint. Here, we report that SC components SYP-3, HTP-3, HIM-3 and HTP-1 are required for a functional synapsis checkpoint...
September 7, 2016: Genetics
https://www.readbyqxmd.com/read/27561390/the-tumour-suppressor-cyld-regulates-the-p53-dna-damage-response
#20
Vanesa Fernández-Majada, Patrick-Simon Welz, Maria A Ermolaeva, Michael Schell, Alexander Adam, Felix Dietlein, David Komander, Reinhard Büttner, Roman K Thomas, Björn Schumacher, Manolis Pasparakis
The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress...
August 26, 2016: Nature Communications
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