scholarly journals ALG-2/AGO-Dependent mir-35 Family Regulates DNA Damage-Induced Apoptosis Through MPK-1/ERK MAPK Signaling Downstream of the Core Apoptotic Machinery in Caenorhabditis elegans

Genetics ◽  
2019 ◽  
pp. genetics.302458.2019 ◽  
Author(s):  
Markus Alexander Doll ◽  
Najmeh Soltanmohammadi ◽  
Björn Schumacher
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Mapk Signaling ◽  
The Core ◽  
Erk Mapk ◽  
Induced Apoptosis

Nickel-induced apoptosis and relevant signal transduction pathways in Caenorhabditis elegans

2010 ◽  
Vol 26 (4) ◽  
pp. 249-256 ◽  
Author(s):  
Cai Kezhou ◽  
Ren Chong ◽  
Yu Zengliang
Keyword(s):  
Signal Transduction ◽  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Cell Apoptosis ◽  
Mapk Signaling ◽  
Signaling Cascades ◽  
Signal Pathways ◽  
C Elegans ◽  
Induced Apoptosis

Many investigations have shown that nickel exposure can induce micronuclei generation, inhibit DNA repair and induce cell apoptosis, both in cells and tissues. However, there is a lack of appropriate in vivo animal models to study the underlying mechanisms of nickel-induced apoptosis. The model organism, Caenorhabditis elegans, has been shown to be a good model for investigating many biological processes. In the present study, we detected 0.01 mM nickel induced significantly germline cell apoptosis after treatment for 12 hours, which demonstrated that C. elegans could be a mammalian in vivo substitute model to study the mechanisms of apoptosis. Then gene knockout C. elegans strains were utilized to investigate the relationship between nickel-induced apoptosis and relevant signal pathways, which were involved in DNA damage and repair, apoptosis regulation and damage signal transduction. The results presented here demonstrated that nickel-induced apoptosis was independent of the DNA damage response gene, such as hus-1, p53/cep-1 and egl-1. The loss-of-function of the genes that related to Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPK) signaling cascades suppressed nickel-induced germline apoptosis, while ERK signaling cascades have no effects on the nickel-induced germline apoptosis.

scholarly journals WITHDRAWN: Caenorhabditis elegans nuclear hormone receptor NHR-14, cooperates with p53/cep-1 to regulate DNA damage-induced apoptosis

Oncotarget ◽  
2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Junling Shen ◽  
Jiaxin Kang ◽  
Zhuang Yao ◽  
Youli Jian ◽  
Yudong Jing ◽  
...  
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Hormone Receptor ◽  
Nuclear Hormone Receptor ◽  
Induced Apoptosis

scholarly journals Caenorhabditis elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-Induced Apoptosis

PLoS Genetics ◽  
2009 ◽  
Vol 5 (6) ◽  
pp. e1000514 ◽  
Author(s):  
Mei Yang ◽  
Jianwei Sun ◽  
Xiaojuan Sun ◽  
Qinfang Shen ◽  
Zhiyang Gao ◽  
...  
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Induced Apoptosis

scholarly journals Functional characterization of Caenorhabditis elegans cbs-2 gene during meiosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pamela Santonicola ◽  
Marcello Germoglio ◽  
Domenico Scotto d’Abbusco ◽  
Adele Adamo
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Functional Characterization ◽  
Genotoxic Stress ◽  
Phenotypic Characterization ◽  
Chromosome Fragmentation ◽  
C Elegans ◽  
Synaptonemal Complex Formation ◽  
Induced Apoptosis

AbstractCystathionine β-synthase (CBS) is a eukaryotic enzyme that maintains the cellular homocysteine homeostasis and catalyzes the conversion of homocysteine to L-cystathionine and Hydrogen sulfide, via the trans-sulfuration pathway. In Caenorhabditis elegans, two cbs genes are present: cbs-1 functions similarly as to human CBS, and cbs-2, whose roles are instead unknown. In the present study we performed a phenotypic characterization of the cbs-2 mutant. The null cbs-2 mutant is viable, fertile and shows the wild-type complement of six bivalents in most oocyte nuclei, which is indicative of a correct formation of crossover recombination. In absence of synaptonemal complex formation (syp-2 mutant), loss of cbs-2 leads to chromosome fragmentation, suggesting that cbs-2 is essential during inter-sister repair. Interestingly, although proficient in the activation of the DNA damage checkpoint after exposure to genotoxic stress, the cbs-2 mutant is defective in DNA damage-induced apoptosis in meiotic germ cells. These results suggest possible functions for CBS-2 in meiosis, distinct from a role in the trans-sulfuration pathway. We propose that the C. elegans CBS-2 protein is required for both inter-sister repair and execution of DNA damage-induced apoptosis.

scholarly journals Low-Dose Triptolide Enhances Bromodomain Inhibitor JQ1-Induced Apoptosis of Acute Myeloid Leukemia Cells Via Down-Regulation of c-Myc Following RAS/MEK/ERK Inhibition

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5757-5757
Author(s):  
Bing Xu ◽  
Yuanfei Shi ◽  
Haijun Zhao ◽  
Yi Qiu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Single Agent ◽  
Mapk Signaling ◽  
Current Therapy ◽  
Apoptosis Pathway ◽  
Erk Mapk ◽  
Induced Apoptosis ◽  
Acute Myeloid

The current therapy for acute myeloid leukemia (AML) remains greatly challengeable because most patients ultimately relapse due to resistant to current chemotherapies. Therefore, development of novel therapies using a variety of agents targeting varying pathways is needed to further improve patients' survival. Here we report that low dose triptolide (TPL), a natural product derived from plant Tripterygium wilfordii, could enhance bromodomain inhibitor JQ1-induced apoptosis of AML cell lines as well as primary cells from patients with de novo and relapsed or refractory (R/R) AML, while sparing their normal counterparts. Moreover, combination of TPL and JQ1 showed a more powerful activity to suppress AML cell growth in a xenograft model than single agent. Mechanistically, the synergetic effects of TPL and JQ1 were associated with impaired mitochondrial membrane potential, increased reactive oxygen species (ROS) production and imbalance of the Bcl2 family of pro-apoptotic and anti-apoptotic proteins, leading to caspase-dependent apoptosis. Meanwhile, RNAseq analysis revealed that ERK/MAPK signaling cascades are responsible for the enhanced activity of TPL in combination with JQ1 against AML. In summary, this study demonstrates that low-dose TPL synergizes with JQ1 to target AML through inhibiting ERK/MAPK signaling and mitochondrial apoptosis pathway, supporting a potential option of combination of TPL and JQ1 for AML treatment. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Caenorhabditis elegans RAD-51 isoform A is required for the induction of DNA-damage-dependent apoptosis

2017 ◽  
Author(s):  
Marcello Germoglio ◽  
Adele Adamo
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Genome Stability ◽  
Protein Isoforms ◽  
Late Development ◽  
Checkpoint Activation ◽  
Late Pachytene ◽  
Alternative Protein ◽  
New Finding ◽  
Induced Apoptosis

AbstractThe rad-51 gene in Caenorhabditis elegans is transcribed into alternative mRNAs potentially coding three alternative protein isoforms. We have genetically modified this gene in order to investigate the potential roles of the longest isoform, namely isoform A, in genome stability. The RAD-51 isoform A appears to contribute to genome stability in late development, but is not implicated in meiosis or DNA repair in the germline. However, the RAD-51 isoform A has a pivotal role in DNA damage induced apoptosis, but not in DNA damage checkpoint activation or physiological cell death. This is a relevant new finding that improves our understanding of how DNA damage apoptosis is restricted to late pachytene stage preventing the inappropriate loss of nuclei undergoing the earlier stages of meiotic recombination, during which a large number of physiologically induced DSBs are present.

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