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https://www.readbyqxmd.com/read/27922110/%C3%AE-h2ax-53bp1-pkap-1-foci-and-their-linear-tracks-induced-by-in-vitro-exposure-to-radon-and-its-progeny-in-human-peripheral-blood-lymphocytes
#1
Defang Ding, Yaping Zhang, Jing Wang, Xufei Wang, Dunhuang Fan, Linfeng He, Xuxia Zhang, Yun Gao, Qiang Li, Honghong Chen
The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27918549/a-hypoxia-responsive-traf6-atm-h2ax-signalling-axis-promotes-hif1%C3%AE-activation-tumorigenesis-and%C3%A2-metastasis
#2
Abdol-Hossein Rezaeian, Chien-Feng Li, Ching-Yuan Wu, Xian Zhang, Jorge Delacerda, M James You, Fei Han, Zhen Cai, Yun Seong Jeong, Guoxiang Jin, Liem Phan, Ping-Chieh Chou, Mong-Hong Lee, Mien-Chie Hung, Dos Sarbassov, Hui-Kuan Lin
The understanding of how hypoxia stabilizes and activates HIF1α in the nucleus with related oncogenic signals could revolutionize targeted therapy for cancers. Here, we find that histone H2AX displays oncogenic activity by serving as a crucial regulator of HIF1α signalling. H2AX interacts with HIF1α to prevent its degradation and nuclear export in order to allow successful VHL-independent HIF1α transcriptional activation. We show that mono-ubiquitylation and phosphorylation of H2AX, which are strictly mediated by hypoxia-induced E3 ligase activity of TRAF6 and ATM, critically regulate HIF1α-driven tumorigenesis...
December 5, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27908383/the-insecticide-spinosad-induces-dna-damage-and-apoptosis-in-hek293-and-hepg2-cells
#3
Mingjun Yang, Guanggang Xiang, Diqiu Li, Yang Zhang, Wenping Xu, Liming Tao
Spinosad, a pesticide acting on the central nervous system of insects, is classified as a pesticide with reduced risk. However, spinosad-induced toxicological effects on non-target organisms must not be ignored. This study aimed to evaluate the cytotoxicity and potential genotoxicity of spinosad in HEK293 and HepG2 cell lines. The results showed that spinosad caused a concentration- and time-dependent decrease in cell viability of HEK293 and HepG2 cells. Spinosad-induced p53 accumulation thereby upregulates the expression of Bax and downregulates the expression of Bcl-2...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27907109/loss-of-h3k9me3-correlates-with-atm-activation-and-histone-h2ax-phosphorylation-deficiencies-in-hutchinson-gilford-progeria-syndrome
#4
Haoyue Zhang, Linlin Sun, Kun Wang, Di Wu, Mason Trappio, Celeste Witting, Kan Cao
Compelling evidence suggests that defective DNA damage response (DDR) plays a key role in the premature aging phenotypes in Hutchinson-Gilford progeria syndrome (HGPS). Studies document widespread alterations in histone modifications in HGPS cells, especially, the global loss of histone H3 trimethylated on lysine 9 (H3K9me3). In this study, we explore the potential connection(s) between H3K9me3 loss and the impaired DDR in HGPS. When cells are exposed to a DNA-damaging agent Doxorubicin (Dox), double strand breaks (DSBs) are generated that result in the phosphorylation of histone H2A variant H2AX (gammaH2AX) within an hour...
2016: PloS One
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#5
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902462/the-synthetic-lethal-killing-of-rad54b-deficient-colorectal-cancer-cells-by-parp1-inhibition-is-enhanced-with-sod1-inhibition
#6
Erin N McAndrew, Chloe C Lepage, Kirk J McManus
Colorectal cancer (CRC) is a leading cause of cancer-related death throughout the world. Despite improved screening efforts, most CRCs are diagnosed at late stages when surgery alone is not curative. Moreover, the low 5-year survival rate (~8-13%) for those living with stage IV CRC highlights the need for better treatment options. Many current chemotherapeutic approaches are non-specific and associated with side effects due to their tendency to target both normal and cancer cells. To address this issue, synthetic lethal (SL) approaches are now being explored in cancer and are defined as the lethal combination of two independently viable mutations/deletions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878300/induction-of-dna-damage-and-apoptosis-in-human-leukemia-cells-by-efavirenz
#7
Ansgar Brüning, Julia Jückstock, Bernd Kost, Panagiotis Tsikouras, Tobias Weissenbacher, Sven Mahner, Ioannis Mylonas
As part of the efforts to drug repurposing, some HIV drugs have recently been identified to exert anticancer effects. Selected nucleoside analogues of nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere with RNA transcription of HI viruses as well as with the replication of DNA in cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are believed to have less effects on human DNA replication and, thus, on cancer cell proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer cells, however, revealed a high sensitivity of leukemia cells to this agent at pharmacologically relevant concentrations of less than 10 µg/ml...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27876069/mgdg-extracted-from-spinach-enhances-the-cytotoxicity-of-radiation-in-pancreatic-cancer-cells
#8
Hiroaki Akasaka, Yoshiyuki Mizushina, Kenji Yoshida, Yasuo Ejima, Naritoshi Mukumoto, Tianyuan Wang, Sachiko Inubushi, Masao Nakayama, Yuki Wakahara, Ryohei Sasaki
BACKGROUND: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. METHODS: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs)...
November 22, 2016: Radiation Oncology
https://www.readbyqxmd.com/read/27853172/lithium-promotes-dna-stability-and-survival-of-ischemic-retinal-neurocytes-by-upregulating-dna-ligase-iv
#9
Ying Yang, Nandan Wu, Sijia Tian, Fan Li, Huan Hu, Pei Chen, Xiaoxiao Cai, Lijun Xu, Jing Zhang, Zhao Chen, Jian Ge, Keming Yu, Jing Zhuang
Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level...
November 17, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27849610/dna-polymerase-%C3%AE-limits-chromosomal-damage-and-promotes-cell-survival-following-aflatoxin-exposure
#10
Ying-Chih Lin, Nichole Owen, Irina G Minko, Sabine S Lange, Liang Li, Michael P Stone, Richard D Wood, Amanda K McCullough, R Stephen Lloyd
Routine dietary consumption of foods that contain aflatoxins is the second leading cause of environmental carcinogenesis worldwide. Aflatoxin-driven mutagenesis is initiated through metabolic activation of aflatoxin B1 (AFB1) to its epoxide form that reacts with N7 guanine in DNA. The resulting AFB1-N7-dG adduct undergoes either spontaneous depurination or imidazole-ring opening yielding formamidopyrimidine AFB1 (AFB1-Fapy-dG). Because this latter adduct is known to persist in human tissues and contributes to the high frequency G-to-T mutation signature associated with many hepatocellular carcinomas, we sought to establish the identity of the polymerase(s) involved in processing this lesion...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27849008/ku70-serine-155-mediates-aurora-b-inhibition-and-activation-of-the-dna-damage-response
#11
Victoria L Fell, Elizabeth A Walden, Sarah M Hoffer, Stephanie R Rogers, Amelia S Aitken, Louisa M Salemi, Caroline Schild-Poulter
The Ku heterodimer (Ku70/Ku80) is the central DNA binding component of the classical non-homologous end joining (NHEJ) pathway that repairs DNA double-stranded breaks (DSBs), serving as the scaffold for the formation of the NHEJ complex. Here we show that Ku70 is phosphorylated on Serine 155 in response to DNA damage. Expression of Ku70 bearing a S155 phosphomimetic substitution (Ku70 S155D) in Ku70-deficient mouse embryonic fibroblasts (MEFs) triggered cell cycle arrest at multiple checkpoints and altered expression of several cell cycle regulators in absence of DNA damage...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27829269/tetrandrine-exerts-a-radiosensitization-effect-on-human-glioma-through-inhibiting-proliferation-by-attenuating-erk-phosphorylation
#12
Ji-Wei Ma, Yong Zhang, Ji-Cheng Ye, Ru Li, Yu-Lin Wen, Jian-Xian Huang, Xue-Yun Zhong
Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence...
November 8, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27826196/the-medicinal-fungus-antrodia-cinnamomea-regulates-dna-repair-and-enhances-the-radiosensitivity-of-human-esophageal-cancer-cells
#13
Yu-Ming Liu, Yu-Kuo Liu, Ling-Wei Wang, Yu-Chuen Huang, Pin-I Huang, Tung-Hu Tsai, Yu-Jen Chen
This study investigated the adjunctive effects of Antrodia cinnamomea mycelial fermentation broth (AC-MFB), a Taiwanese medicinal fungus, in enhancing the radiosensitivity of esophageal cancer cells. Human CE81T/VGH squamous and BE3 adenocarcinoma esophageal cancer cells were used in this study. A colony formation assay showed that pretreatment with AC-MFB decreased the survival of irradiated esophageal cancer cells, with a maximum sensitizer enhancement ratio of 1.91% and 37% survival. A DNA histogram study showed that AC-MFB pretreatment enhanced cell cycle arrest at the G2/M phase, the most radiosensitive phase...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27821478/mcl-1-depletion-impairs-dna-dsb-repair-and-re-initiation-of-stalled-dna-replication-forks
#14
Abid R Mattoo, Raj K Pandita, Sharmistha Chakraborty, Vijaya Charaka, Kalpana Mujoo, Clayton R Hunt, Tej K Pandita
Myeloid cell leukemia-1 : MCL-1) is a pro-survival BCL-2 protein family member highly expressed in hematopoietic stem cells (HSCs) and regulated by growth factor signals that manifest anti-apoptotic activity. Here we report that depletion of MCL-1, but not its isoform MCL1S, increases genomic instability and cell sensitivity to ionizing radiation (IR) induced death. MCL-1 association with genomic DNA increased post-irradiation and it co-localized with 53BP1 in foci. Post-irradiation, MCL-1 depleted cells exhibited decreased γ-H2AX foci, decreased phosphorylation of ATR and higher levels of residual 53BP1 and RIF1 foci, suggesting DNA DSB repair by homologous recombination (HR) was compromised...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27815899/dna-damage-response-resulting-from-replication-stress-induced-by-synchronization-of-cells-by-inhibitors-of-dna-replication-analysis-by-flow-cytometry
#15
Dorota Halicka, Hong Zhao, Jiangwei Li, Jorge Garcia, Monika Podhorecka, Zbigniew Darzynkiewicz
Cell synchronization is often achieved by transient inhibition of DNA replication. When cultured in the presence of such inhibitors as hydroxyurea, aphidicolin or excess of thymidine the cells that become arrested at the entrance to S-phase upon release from the block initiate progression through S then G2 and M. However, exposure to these inhibitors at concentrations commonly used to synchronize cells leads to activation of ATR and ATM protein kinases as well as phosphorylation of Ser139 of histone H2AX. This observation of DNA damage signaling implies that synchronization of cells by these inhibitors is inducing replication stress...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27814570/chromosomal-aberrations-clastogens-vs-aneugens
#16
Masayuki Mishima
Current anticancer therapy may be one of the most important exogenous sources of exposure to genotoxic agents in US, Japan, and Europe, where approximately 40-55 percent of the population is diagnosed with cancer at a certain point in their life. This review focuses on recent efforts to integrate a novel biomarker, gamma-H2AX, into anticancer drug screening to classify the mode of action (MoA) for genotoxic outcome into clastogenicity and aneugenicity, a distinction that has considerable impact on risk assessment and control strategy...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/27813335/phosphorylation-of-h2a-x-tyr39-positively-regulates-dna-damage-response-and-is-linked-to-cancer-progression
#17
Yan Liu, Yue-Hong Long, Shu-Qing Wang, Yu-Feng Li, Jing-Hua Zhang
Double-stranded DNA breaks induce serine phosphorylation of histone H2A.X, producing γ-H2A.X foci that are then recognised by DNA damage response pathway proteins. Formation of γ-H2A.X is therefore critical for the repair of DNA double-stranded breaks and maintenance of genomic stability, and defects in the recognition or repair of double-stranded breaks can result in tumorigenesis. However, key details regarding the formation of γ-H2A.X and its possible role in tumorigenesis remain elusive. Here, we report a previously unknown phosphorylation site on H2A...
November 4, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27812868/detection-of-dysfunctional-telomeres-in-oncogene-induced-senescence
#18
Priyanka L Patel, Utz Herbig
Expressing oncogenes in normal somatic human cells leads to cellular senescence after just a few cell division cycles. In cells that are more resistant to culture stresses, such as human dermal fibroblasts, this oncogene-induced senescence (OIS) is a result of a DNA damage response (DDR) that is activated due to the formation of DNA lesions at both non-telomeric and telomeric DNA sequences. DNA lesions can be visualized as DDR foci by immunofluorescence microscopy using antibodies against a number of DDR factors, including ϒ-H2AX and 53BP1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27807597/analysis-of-the-interplay-between-all-trans-retinoic-acid-and-histone-deacetylase-inhibitors-in-leukemic-cells
#19
Katrin Noack, Nisintha Mahendrarajah, Dorle Hennig, Luisa Schmidt, Florian Grebien, Dagmar Hildebrand, Markus Christmann, Bernd Kaina, Andreas Sellmer, Siavosh Mahboobi, Katharina Kubatzky, Thorsten Heinzel, Oliver H Krämer
The treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) induces granulocytic differentiation. This process renders APL cells resistant to cytotoxic chemotherapies. Epigenetic regulators of the histone deacetylases (HDACs) family, which comprise four classes (I-IV), critically control the development and progression of APL. We set out to clarify the parameters that determine the interaction between ATRA and histone deacetylase inhibitors (HDACi). Our assays included drugs against class I HDACs (MS-275, VPA, and FK228), pan-HDACi (LBH589, SAHA), and the novel HDAC6-selective compound Marbostat-100...
November 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27806616/development-of-a-transmission-alpha-particle-dosimetry-technique-using-a549-cells-and-a-ra-223-source-for-targeted-alpha-therapy
#20
R Al Darwish, A H Staudacher, Y Li, M P Brown, E Bezak
PURPOSE: In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells...
November 2016: Medical Physics
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