scholarly journals ATM Induces Cell Death with Autophagy in Response to H2O2 Specifically in Caenorhabditis elegans Nondividing Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Takahito Moriwaki ◽  
Akira Yamasaki ◽  
Qiu-Mei Zhang-Akiyama
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Somatic Cells ◽  
Dead Cell ◽  
C Elegans ◽  
Cell Staining ◽  
Dna Damaging Agents ◽  
Gfp Reporter ◽  
Wide Range ◽  
Reporter Assays

Introduction. Ataxia-telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response and is directly activated by reactive oxygen species (ROSs) in addition to DNA double-stranded breaks. However, the physiological function of the response to ROSs is not understood. Purpose. In the present study, we investigated how ATM responds to ROSs in Caenorhabditis elegans (C. elegans). Materials and Methods. First, we measured sensitivities of larvae to DNA-damaging agents and ROSs. Next, we analyzed the drug sensitivities of fully matured adult worms, which consist of nondividing somatic cells. Dead cell staining with acridine orange was performed to visualize the dead cells. In addition, we performed GFP reporter assays of lgg-1, an autophagy-related gene, to determine the types of cell death. Results. atm-1(tm5027) larvae showed a wide range of sensitivities to both DNA-damaging agents and ROSs. In contrast, fully matured adult worms, which consist of nondividing somatic cells, showed sensitivity to DNA-damaging agent, NaHSO3, but they showed resistance to H2O2. Dead cell staining and GFP reporter assays of lgg-1 suggest that C. elegans ATM-1 induces the cell death with autophagy in intestinal cells in response to H2O2. Conclusion. We revealed that ATM induces cell death in response to H2O2.

scholarly journals Characterization of the phototoxicity, chemigenetic profile, and mutational signatures of the chemotherapeutic CX-5461 in Caenorhabditis elegans

2019 ◽  
Author(s):  
Frank B. Ye ◽  
Akil Hamza ◽  
Tejomayee Singh ◽  
Stephane Flibotte ◽  
Philip Hieter ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cancer Therapeutics ◽  
Copy Number Variations ◽  
Factors Affecting ◽  
C Elegans ◽  
Dna Damaging Agents ◽  
Wide Range ◽  
Anti Cancer ◽  
Exogenous Factors

ABSTRACTNew anti-cancer therapeutics require extensive in vivo characterization to identify endogenous and exogenous factors affecting efficacy, to measure toxicity and mutagenicity, and to determine genotypes resulting in therapeutic sensitivity or resistance. We used Caenorhabditis elegans as a platform with which to characterize properties of anti-cancer therapeutic agents in vivo. We generated a map of chemigenetic interactions between DNA damage response mutants and common DNA damaging agents. We used this map to investigate the properties of the new anti-cancer therapeutic CX-5461. We phenocopied the photoreactivity observed in CX-5461 clinical trials and found that CX-5461 generates reactive oxygen species when exposed to UVA radiation. We demonstrated that CX-5461 is a mutator, resulting in both large copy number variations and a high frequency of single nucleotide variations (SNVs). CX-5461-induced SNVs exhibited a distinct mutational signature. Consistent with the wide range of CX-5461-induced mutation types, we found that multiple repair pathways were needed for CX-5461 tolerance. Together, the data from C. elegans demonstrate that CX-5461 is a multimodal DNA damaging agent with strong similarity to ellipticines, a class of antineoplastic agents, and to anthracycline-based chemotherapeutics.

scholarly journals Autonomous and non-autonomous roles of DNase II during cell death in C. elegans embryos

2015 ◽  
Vol 35 (3) ◽  
Author(s):  
Hsiang Yu ◽  
Huey-Jen Lai ◽  
Tai-Wei Lin ◽  
Szecheng J. Lo
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Fluorescence Probes ◽  
Dna Fragments ◽  
Dnase Ii ◽  
C Elegans ◽  
Dying Cells

The method of ToLFP (topoisomerase labelled fluorescence probes) is useful for detecting the DNA fragments generated by DNase II in Caenorhabditis elegans embryos. It reveals ~70% ToLFP signals in dying cells and 30% in engulfing cells during embryogenesis.

scholarly journals Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 1011-1022 ◽  
Author(s):  
T.L. Gumienny ◽  
E. Lambie ◽  
E. Hartwieg ◽  
H.R. Horvitz ◽  
M.O. Hengartner
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Somatic Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Mapk Pathway ◽  
Apoptotic Cell ◽  
C Elegans ◽  
Pathway Activation

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

scholarly journals Ferrous-glutathione coupling mediates ferroptosis and frailty in Caenorhabditis elegans

2019 ◽  
Author(s):  
Nicole L. Jenkins ◽  
Simon A. James ◽  
Agus Salim ◽  
Fransisca Sumardy ◽  
Terence P. Speed ◽  
...  
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Ferrous Iron ◽  
Somatic Tissue ◽  
Glutathione Depletion ◽  
Death Process ◽  
C Elegans ◽  
Regulated Cell Death ◽  
Age Related ◽  
Ageing Rate

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis1, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in the Caenorhabditis elegans model of ageing2. Here we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan in C. elegans. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant ageing rate. Because excess age-related iron elevation in somatic tissue, particularly in brain3–5, is thought to contribute to degenerative disease6, 7, our data indicate that post-developmental interventions to limit ferroptosis may promote healthy ageing.

Creation of Low-Copy Integrated Transgenic Lines in Caenorhabditis elegans

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1217-1226 ◽  
Author(s):  
Vida Praitis ◽  
Elizabeth Casey ◽  
David Collar ◽  
Judith Austin
Keyword(s):  
Caenorhabditis Elegans ◽  
Expression Level ◽  
Dna Arrays ◽  
Extrachromosomal Dna ◽  
C Elegans ◽  
Microparticle Bombardment ◽  
Alternative Method ◽  
Extrachromosomal Array ◽  
Gfp Reporter ◽  
Transgenic Lines

Abstract In Caenorhabditis elegans, transgenic lines are typically created by injecting DNA into the hermaphrodite germline to form multicopy extrachromosomal DNA arrays. This technique is a reliable means of expressing transgenes in C. elegans, but its use has limitations. Because extrachromosomal arrays are semistable, only a fraction of the animals in a transgenic extrachromosomal array line are transformed. In addition, because extrachromosomal arrays can contain hundreds of copies of the transforming DNA, transgenes may be overexpressed, misexpressed, or silenced. We have developed an alternative method for C. elegans transformation, using microparticle bombardment, that produces single- and low-copy chromosomal insertions. Using this method, we find that it is possible to create integrated transgenic lines that reproducibly express GFP reporter constructs without the variations in expression level and pattern frequently exhibited by extrachromosomal array lines. In addition, we find that low-copy integrated lines can also be used to express transgenes in the C. elegans germline, where conventional extrachromosomal arrays typically fail to express due to germline silencing.

Two C. elegans genes control the programmed deaths of specific cells in the pharynx

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 591-603 ◽  
Author(s):  
R.E. Ellis ◽  
H.R. Horvitz
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Programmed Cell Death ◽  
Nematode Caenorhabditis Elegans ◽  
Genetic Studies ◽  
C Elegans

The genes ces-1 and ces-2 control the decisions of two cells in the nematode Caenorhabditis elegans to undergo programmed cell death. Mutations that cause a gain of ces-1 function or a reduction of ces-2 function prevent these cells, the sisters of the two pharyngeal NSM neurons, from dying. These mutations do not affect most other cell deaths. Genetic studies indicate that ces-1 and ces-2 affect the fates of the NSM sisters by regulating the genes required for all programmed cell deaths to occur.

scholarly journals Bacterial second messenger 3′,5′-cyclic diguanylate attracts Caenorhabditis elegans and suppresses its immunity

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Joseph Angeloni ◽  
Yuqing Dong ◽  
Zeneng Wang ◽  
Min Cao
Keyword(s):  
Caenorhabditis Elegans ◽  
High Rate ◽  
Bacterial Invasion ◽  
Signal Molecules ◽  
Cyclic Diguanylate ◽  
C Elegans ◽  
Low Concentrations ◽  
Wide Range ◽  
Interkingdom Communication

AbstractCyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. In this study, we found that Caenorhabditis elegans can detect and are attracted to multiple signal molecules produced by Vibrio cholerae, specifically the 3′,5′-cyclic diguanylate (c-di-GMP), even though this bacterium kills the host at a high rate. C-di-GMP is sensed through C. elegans olfactory AWC neurons, which then evokes a series of signal transduction pathways that lead to reduced activity of two key stress response transcription factors, SKN-1 and HSF-1, and weakened innate immunity. Taken together, our study elucidates the role of c-di-GMP in interkingdom communication. For C. elegans, bacterial c-di-GMP may serve as a cue that they can use to detect food. On the other hand, preexposure to low concentrations of c-di-GMP may impair their immune response, which could facilitate bacterial invasion and survival.

Morphology of programmed cell death in the ventral nerve cord of Caenorhabditis elegans larvae

Development ◽  
1982 ◽  
Vol 67 (1) ◽  
pp. 89-100
Author(s):  
Alison M. G. Robertson ◽  
J. N. Thomson
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Programmed Cell Death ◽  
Ultrastructural Study ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Condensed Chromatin ◽  
C Elegans ◽  
Programmed Death ◽  
Selection Of

In the nematode C. elegans, cells undergoing programmed death in the developing ventral nerve cord were identified by Nomarski optics and prepared for ultrastructural study at various times after their birth in mitosis. The sequence of changes observed suggests that the hypodermis recognizes the dying cell before completion of telophase. The dying cell is engulfed and digestion then occurs until all that remains within the hypodermal cytoplasm is a collection of membranous whorls interspersed with condensed chromatin-like remnants. The process shares several features with apoptosis, the mode of programmed cell death observed in vertebrates and insects. The selection of cells for programmed death appears not to involve competition for peripheral targets.

scholarly journals Regulators of the Actin Cytoskeleton Mediate Lethality in a Caenorhabditis elegans dhc-1 Mutant

2010 ◽  
Vol 21 (15) ◽  
pp. 2707-2720 ◽  
Author(s):  
Aleksandra J. Gil-Krzewska ◽  
Erica Farber ◽  
Edgar A. Buttner ◽  
Craig P. Hunter
Keyword(s):  
Caenorhabditis Elegans ◽  
Actin Cytoskeleton ◽  
Cytoplasmic Dynein ◽  
Loss Of Function ◽  
Cellular Functions ◽  
Capping Protein ◽  
C Elegans ◽  
Wide Range ◽  
Actin Capping Protein ◽  
Associated Proteins

Functional analysis of cytoplasmic dynein in Caenorhabditis elegans has revealed a wide range of cellular functions for this minus-end–directed motor protein. Dynein transports a variety of cargos to diverse cellular locations, and thus cargo selection and destination are likely regulated by accessory proteins. The microtubule-associated proteins LIS-1 and dynein interact, but the nature of this interaction remains poorly understood. Here we show that both LIS-1 and the dynein heavy-chain DHC-1 are required for integrity of the actin cytoskeleton in C. elegans. Although both dhc-1(or195ts) and lis-1 loss-of-function disrupt the actin cytoskeleton and produce embryonic lethality, a double mutant suppresses these defects. A targeted RNA interference screen revealed that knockdown of other actin regulators, including actin-capping protein genes and prefoldin subunit genes, suppresses dhc-1(or195ts)–induced lethality. We propose that release or relocation of the mutant dynein complex mediates this suppression of dhc-1(or195ts)--induced phenotypes. These results reveal an unexpected direct or indirect interaction between the actin cytoskeleton and dynein activity.

scholarly journals Worms, Fat, and Death: Caenorhabditis elegans Lipid Metabolites Regulate Cell Death

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 125
Author(s):  
Marcos A. Perez ◽  
Jennifer L. Watts
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Genetic Pathways ◽  
C Elegans ◽  
Regulated Cell Death ◽  
Dietary Polyunsaturated Fatty Acids ◽  
Dependent Form ◽  
Lipid Metabolites ◽  
Regulate Cell Death

Caenorhabditis elegans is well-known as the model organism used to elucidate the genetic pathways underlying the first described form of regulated cell death, apoptosis. Since then, C. elegans investigations have contributed to the further understanding of lipids in apoptosis, especially the roles of phosphatidylserines and phosphatidylinositols. More recently, studies in C. elegans have shown that dietary polyunsaturated fatty acids can induce the non-apoptotic, iron-dependent form of cell death, ferroptosis. In this review, we examine the roles of various lipids in specific aspects of regulated cell death, emphasizing recent work in C. elegans.

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