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https://www.readbyqxmd.com/read/29786770/the-extract-of-leonurus-sibiricus-transgenic-roots-with-atpap1-transcriptional-factor-induces-apoptosis-via-dna-damage-and-down-regulation-of-selected-epigenetic-factors-in-human-cancer-cells
#1
Przemysław Sitarek, Tomasz Kowalczyk, Simona Santangelo, Adam J Białas, Monika Toma, Joanna Wieczfinska, Tomasz Śliwiński, Ewa Skała
The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels...
May 21, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29780501/a-bi-terminal-protein-ligation-strategy-to-probe-chromatin-structure-during-dna-damage
#2
Sinan Kilic, Iuliia Boichenko, Carolin C Lechner, Beat Fierz
The cellular response to DNA damage results in a signaling cascade that primes chromatin for repair. Combinatorial post-translational modifications (PTMs) play an important role in this process by altering the physical properties of chromatin and recruiting downstream factors. One key signal integrator is the histone variant H2A.X, which is phosphorylated at a C-terminal serine (S139ph), and ubiquitylated within its N-terminal tail at lysines 13 and 15 (K13/15ub). How these PTMs directly impact chromatin structure and thereby facilitate DNA repair is not well understood...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29771500/rational-design-of-cancer-targeted-selenadiazole-derivative-as-efficient-radiosensitizer-for-precise-cancer-therapy
#3
Delong Zeng, Shulin Deng, Chengcheng Sang, Jianfu Zhao Zhao, Tianfeng Chen
Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of targeted therapies for personalized cancer medicine. Herein, cancer targeting RGD peptide has been covalently conjugated to selenadiazole derivative (RGD-SeD) to improve its cancer selectivity. The RGD decoration significantly enhances the anticancer efficacy of RGD-SeD in αVβ3 integrin-overexpressing HepG2 liver cancer cells, but not in normal liver cells. Cellular uptake assay and fluorescent imaging confirmed the selectivity of RGD-SeD to integrin overexpressing cancer cells...
May 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#4
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29764934/structure-specific-recognition-protein-1-ssrp1-is-an-elongated-homodimer-that-binds-histones
#5
Gabriele Marcianò, Stefano Da Vela, Giancarlo Tria, Dmitri I Svergun, Olwyn Byron, Danny T Huang
The histone chaperone complex facilitates chromatin transcription (FACT) plays important roles in DNA repair, replication, and transcription. In the formation of this complex, structure-specific recognition protein-1 (SSRP1) heterodimerizes with suppressor of Ty 16 (SPT16). SSRP1 also has SPT16-independent functions, but how SSRP1 functions alone remains elusive. Here, using analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS) techniques, we characterized human SSRP1 and that from the amoeba Dictyostelium discoideum and show that both orthologs form an elongated homodimer in solution...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29742439/norc-recruitment-by-h2a-x-deposition-at-rrna-gene-promoter-limits-embryonic-stem-cell-proliferation
#6
Boris Eleuteri, Sergi Aranda, Patrik Ernfors
Embryonic stem cells (ESCs) display an abbreviated cell cycle, resulting in a short doubling time and rapid proliferation. The histone variant H2A.X is critical for proliferation of stem cells, although mechanistic insights have remained obscure. Here, we show that H2A.X defines the rate of mouse ESC proliferation independently of the DNA damage response pathway, and it associates with three major chromatin-modifying complexes. Our functional and biochemical analyses demonstrate that H2A.X-associated factors mediate the H2A...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29707605/scaling-up-to-study-brca2-the-zeppelin-zebrafish-mutant-reveals-a-role-for-brca2-in-embryonic-development-of-kidney-mesoderm
#7
Bridgette E Drummond, Rebecca A Wingert
Specialized renal epithelial cells known as podocytes are essential components of the filtering structures within the kidney that coordinate the process of removing waste from the bloodstream. Podocyte loss initiates many human kidney diseases as it triggers subsequent damage to the kidney, leading to progressive loss of function that culminates with end stage renal failure. Podocyte morphology, function and gene expression profiles are well conserved between zebrafish and humans, making the former a relevant model to study podocyte development and model kidney diseases...
2018: Cancer Cell & Microenvironment
https://www.readbyqxmd.com/read/29676825/histone-chaperones-play-crucial-roles-in-maintenance-of-stem-cell-niche-during-plant-root-development
#8
Jing Ma, Yuhao Liu, Wangbin Zhou, Yan Zhu, Aiwu Dong, Wen-Hui Shen
Stem cells in both plant and animal kingdoms reside in a specialized cellular context called stem-cell niche (SCN). SCN integrity is crucial for organism development. Here we show that the H3/H4 histone chaperone CHROMATIN ASSEMBLY FACTOR-1 (CAF-1) and the H2A/H2B histone chaperone NAP1-RELATED PROTEIN1/2 (NRP1/2) play synergistic roles in Arabidopsis root SCN maintenance. Compared to either the m56-1 double mutant deprived of NRP1 and NRP2 or the fas2-4 mutant deprived of CAF-1, the combined m56-1fas2-4 triple mutant displayed a much more severe short-root phenotype...
April 20, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29668110/phenylbutyl-isoselenocyanate-induces-reactive-oxygen-species-to-inhibit-androgen-receptor-and-to-initiate-p53-mediated-apoptosis-in-lncap-prostate-cancer-cells
#9
Wei Wu, Deepkamal Karelia, Kartick Pramanik, Shantu G Amin, Arun K Sharma, Cheng Jiang, Junxuan Lu
Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNCaP prostate cancer cells with ISC-4 and examined their apoptosis responses, and interrogated the signaling mechanisms through pharmacological and siRNA knockdown approaches. Our results show that ISC-4 was more potent at inducing apoptosis than its sulfur analog phenylbutyl isothiocyanate (PBITC) without suppressing protein kinase AKT Ser473 phosphorylation...
April 18, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29644260/biochemical-analysis-of-dimethyl-suberimidate-crosslinked-yeast-nucleosomes
#10
Yuichi Ichiakwa, Paul D Kaufman
Nucleosomes are the fundamental unit of eukaryotic chromosome packaging, comprised of 147 bp of DNA wrapped around two molecules of each of the core histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis of symmetry centered on the homodimeric interaction between the C-termini of the H3 molecules. To explore the functional consequences of nucleosome symmetry, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, allowing us to compare cells with single or double H3 alterations...
March 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29630045/investigation-of-protein-recruitment-to-dna-lesions-using-405-nm-laser-micro-irradiation
#11
Antoine Gaudreau-Lapierre, Daniel Garneau, Billel Djerir, Frédéric Coulombe, Théo Morin, Alexandre Marechal
The DNA Damage Response (DDR) uses a plethora of proteins to detect, signal, and repair DNA lesions. Delineating this response is critical to understand genome maintenance mechanisms. Since recruitment and exchange of proteins at lesions are highly dynamic, their study requires the ability to generate DNA damage in a rapid and spatially-delimited manner. Here, we describe procedures to locally induce DNA damage in human cells using a commonly available laser-scanning confocal microscope equipped with a 405 nm laser line...
March 20, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29616291/the-role-of-hepatic-cytochrome-p450s-in-the-cytotoxicity-of-dronedarone
#12
Si Chen, Qiangen Wu, Baitang Ning, Matthew Bryant, Lei Guo
Dronedarone is used to treat patients with cardiac arrhythmias and has been reported to be associated with liver injury. Our previous mechanistic work demonstrated that DNA damage-induced apoptosis contributes to the cytotoxicity of dronedarone. In this study, we examined further the underlying mechanisms and found that after a 24-h treatment of HepG2 cells, dronedarone caused cytotoxicity, G1-phase cell cycle arrest, suppression of topoisomerase II, and DNA damage in a concentration-dependent manner. We also investigated the role of cytochrome P450s (CYPs)-mediated metabolism in the dronedarone-induced toxicity using our previously established HepG2 cell lines expressing individually 14 human CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7)...
April 3, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29549088/evolutionary-origins-and-diversification-of-testis-specific-short-histone-h2a-variants-in-mammals
#13
Antoine Molaro, Janet M Young, Harmit S Malik
Eukaryotic genomes must accomplish both compact packaging for genome stability and inheritance, as well as accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3, and H4) and by deploying histone variants with specialized chromatin functions. Some histone variants are conserved across all eukaryotes, whereas others are lineage-specific. Here, we performed detailed phylogenomic analyses of "short H2A histone" variants found in mammalian genomes...
April 2018: Genome Research
https://www.readbyqxmd.com/read/29515758/expression-of-tdrd9-in-a-subset-of-lung-carcinomas-by-cpg-island-hypomethylation-protects-from-dna-damage
#14
Macarena Guijo, María Ceballos-Chávez, Elena Gómez-Marín, Laura Basurto-Cayuela, José C Reyes
Tudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline, where it is involved in the biosynthesis of PIWI-interacting RNAs (piRNAs). Here, we show that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas and derived cell lines by hypomethylation of its CpG island. Furthermore, TDRD9 expression is associated with poor prognosis in lung adenocarcinoma. We find that downregulation of TDRD9 expression in TDRD9-positive cell lines causes a decrease in cell proliferation, S-phase cell cycle arrest, and apoptosis...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29495465/post-translational-modifications-of-h2a-histone-variants-and-their-role-in-cancer
#15
REVIEW
David Corujo, Marcus Buschbeck
Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core...
February 27, 2018: Cancers
https://www.readbyqxmd.com/read/29436614/arctigenin-inhibits-the-activation-of-the-mtor-pathway-resulting-in-autophagic-cell-death-and-decreased-er-expression-in-er-positive-human-breast-cancer-cells
#16
Thressi Maxwell, Kyu Shik Lee, Soyoung Kim, Kyung-Soo Nam
Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer...
April 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29434792/pine-needle-oil-induces-g2-m-arrest-of-hepg2-cells-by-activating-the-atm-pathway
#17
Bing Qiu, Wei Jiang, Wenliang Qiu, Wenling Mu, Yujing Qin, Yongcui Zhu, Jianying Zhang, Qingyi Wang, Dongjie Liu, Zhangyi Qu
Over the last two decades, inducing DNA damage of cancer cells by natural medicines has become a research hotspot in the field of cancer treatment. Although various natural medicines have anticancer effects, very few studies have been conducted to explore the anti-cancer effect of pine needle oil. In the present study, the role of pine needle oil in inducing G2/M arrest in HepG2 cells was investigated. The data revealed that pine needle oil could induce DNA damage in a dose-dependent manner. In the pine needle oil-treated HepG2 cells, the protein levels of phosphorylated (p)-ataxia-telangiectasia mutated (ATM), γ-H2A histone family, member X, p-p53, p-checkpoint kinase 2 and p-cell division cycle 25C were evidently increased, indicating that pine needle oil facilitated G2/M arrest in HepG2 cells through the ATM pathway...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29397942/senescence-messaging-secretome-factors-trigger-premature-senescence-in-human-endometrium-derived-stem-cells
#18
Irina O Vassilieva, Galina F Reshetnikova, Alla N Shatrova, Nataliya V Tsupkina, Marianna V Kharchenko, Larisa L Alekseenko, Nikolay N Nikolsky, Elena B Burova
Accumulating evidence suggests that the senescence-messaging secretome (SMS) factors released by senescent cells play a key role in cellular senescence and physiological aging. Phenomenon of the senescence induction in human endometrium-derived mesenchymal stem cells (MESCs) in response to SMS factors has not yet been described. In present study, we examine a hypothesis whether the conditioned medium from senescent cells (CM-old) may promote premature senescence of young MESCs. In this case, we assume that SMS factors, containing in CM-old are capable to trigger senescence mechanism in a paracrine manner...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29396562/cytochrome-c-oxidase-deficiency-oxidative-stress-possible-antioxidant-therapy-and-link-to-nuclear-dna-damage
#19
Liza Douiev, Bassam Abu-Libdeh, Ann Saada
In response to Ravera et al. "Fanconi anemia: from DNA repair to metabolism" commenting on our recent publication by Abu-Libdeh, Douiev et al., describing a pathogenic variant in the COX 4I1 gene simulating Fanconi anemia, we wish to add supplementary, pertinent information linking cytochrome c oxidase (COX, mitochondrial respiratory chain complex IV) dysfunction to oxidative stress and nuclear DNA damage. Elevated production of reactive oxygen species (ROS) in COX 4I1 deficient fibroblasts was detected in cells grown in glucose free medium and normalized by ascorbate or N-acetylcysteine supplementation...
April 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29394262/synthesis-and-characterization-of-a-magnetic-adsorbent-from-negatively-valued-iron-mud-for-methylene-blue-adsorption
#20
Jiancong Liu, Yang Yu, Suiyi Zhu, Jiakuan Yang, Jian Song, Wei Fan, Hongbin Yu, Dejun Bian, Mingxin Huo
With increasing awareness of reduction of energy and CO2 footprint, more waste is considered recyclable for generating value-added products. Here we reported the negatively-valued iron mud, a waste from groundwater treatment plant, was successfully converted into magnetic adsorbent. Comparing with the conventional calcination method under the high temperature and pressure, the synthesis of the magnetic particles (MPs) by Fe2+/Fe3+ coprecipitation was conducted at environment-friendly condition using ascorbic acid (H2A) as reduction reagent and nitric acid (or acid wastewater) as leaching solution...
2018: PloS One
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