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Dna repair and autophagy

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https://www.readbyqxmd.com/read/29329412/lhx8-ablation-leads-to-massive-autophagy-of-mouse-oocytes-associated-with-dna-damage
#1
Emanuele Pelosi, Laura D'Ignazio, Marc Michel, Melissa Beyer, Kassimier Thompson, Antonino Forabosco, David Schlessinger
Following proliferation of oogonia in mammals, great numbers of germ cells are discarded, primarily by apoptosis, while the remainder form primordial follicles (the ovarian reserve) that determine fertility and reproductive lifespan. More massive, rapid, and essentially total loss of oocytes, however, occurs when the transcription factor Lhx8 is ablated-though the cause and mechanism of germ cell loss from the Lhx8-/- ovaries has been unknown. We found that Lhx8-/- ovaries maintain the same number of germ cells throughout embryonic development; rapid decrease in the pool of oocytes starts shortly before birth...
January 10, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29316551/chloroquine-enhances-the-radiosensitivity-of-bladder-cancer-cells-by-inhibiting-autophagy-and-activating-apoptosis
#2
Feng Wang, Jinyuan Tang, Pengchao Li, Shuhui Si, Hao Yu, Xiao Yang, Jun Tao, Qiang Lv, Min Gu, Haiwei Yang, Zengjun Wang
BACKGROUND/AIMS: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. METHODS: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors...
December 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#3
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29277783/up-regulation-of-uvrag-by-hdac1-inhibition-attenuates-5fu-induced-cell-death-in-hct116-colorectal-cancer-cells
#4
Yoon Kyung Jo, Na Yeon Park, Ji Hyun Shin, Doo Sin Jo, Ji-Eun Bae, Eun Sun Choi, Sungho Maeng, Hong Bae Jeon, Seon Ae Roh, Jong Wook Chang, Jin Cheon Kim, Dong-Hyung Cho
The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29277777/amifostine-protects-mouse-liver-against-radiation-induced-autophagy-blockage
#5
Michael I Koukourakis, Alexandra Giatromanolaki, Konstantina Fylaktakidou, Maria Kouroupi, Efthimios Sivridis, Christos E Zois, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Ilias V Karagounis, Konstantinos Simopoulos, David J P Ferguson, Adrian L Harris
BACKGROUND/AIM: Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. MATERIALS AND METHODS: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. RESULTS: The study provides evidence that ionizing radiation blocks autophagy activity and lysosomal biogenesis in normal mouse liver...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29258892/enhanced-repair-of-uv-induced-dna-damage-by-1-25-dihydroxyvitamin-d3-in-skin-is-linked-to-pathways-that-control-cellular-energy
#6
Mark Stephen Rybchyn, Warusavithana Gunawardena Manori De Silva, Vanessa Bernadette Sequeira, Bianca Yuko McCarthy, Anthony Vincent Dilley, Katie Marie Dixon, Gary Mark Halliday, Rebecca Sara Mason
Inadequately repaired post-UV DNA damage results in skin cancers. DNA repair requires energy but skin cells have limited capacity to produce energy after UV insult. We examined whether energy supply is important for DNA repair after UV exposure, in the presence of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which reduces UV-induced DNA damage and photocarcinogenesis in a variety of models. After UV exposure of primary human keratinocytes, the addition of 1,25(OH)2D3 increased unscheduled DNA synthesis, a measure of DNA repair...
December 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29232380/inhibition-of-grp78-abrogates-radioresistance-in-oropharyngeal-carcinoma-cells-after-egfr-inhibition-by-cetuximab
#7
Chaonan Sun, Chuyang Han, Yuanjun Jiang, Ning Han, Miao Zhang, Guang Li, Qiao Qiao
The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER) homeostatic state and result in ER stress (ERS), subsequently causing resistance to radiation and drugs...
2017: PloS One
https://www.readbyqxmd.com/read/29216538/tip60-contributes-to-porcine-embryonic-development-by-regulating-dna-damage-response
#8
Jing Guo, Wenjun Zhou, Ying-Jie Niu, Kyung-Tae Shin, Young Tae Heo, Nam-Hyung Kim, Xiang-Shun Cui
The acetyltransferase TIP60 (also known as Kat5) is a member of the MYST family of histone acetyltransferases and was initially identified as a cellular protein. TIP60 acetylates histone and non-histone proteins and is involved in diverse biological processes, including apoptosis, cell cycle, and DNA damage responses. In this study, a specific inhibitor of TIP60 was used to detect the function of TIP60 in porcine parthenogenetic embryos. The results showed that TIP60 inhibition impaired porcine parthenogenetic embryonic development...
December 2, 2017: Theriogenology
https://www.readbyqxmd.com/read/29180765/the-inhibitory-effect-of-minocycline-on-radiation-induced-neuronal-apoptosis-via-ampk%C3%AE-1-signaling-mediated-autophagy
#9
Liyuan Zhang, Ping Huang, Hui Chen, Wen Tan, Jiawei Lu, Wei Liu, Jingdong Wang, Shuyu Zhang, Wei Zhu, Jianping Cao, Ye Tian, Hongying Yang
Due to an increasing concern about radiation-induced cognitive deficits for brain tumor patients receiving radiation therapy, developing and evaluating countermeasures has become inevitable. Our previous study has found that minocycline, a clinical available antibiotics that can easily cross the blood brain barrier, mitigates radiation-induced long-term memory loss in rats, accompanied by decreased hippocampal neuron apoptosis. Thus, in the present study, we report an unknown mechanism underlying the neuroprotective effect of minocycline...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#10
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29149404/the-translational-controlled-tumour-protein-tctp-biological-functions-and-regulation
#11
Ulrich-Axel Bommer
The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29129070/molecular-signatures-associated-with-treatment-of-triple-negative-mda-mb231-breast-cancer-cells-with-histone-deacetylase-inhibitors-jaha-and-saha
#12
Mariangela Librizzi, Fabio Caradonna, Ilenia Cruciata, Janusz Dębski, Supojjanee Sansook, Michał Dadlez, John Spencer, Claudio Luparello
Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN(1)-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA's cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 μM. JAHA's lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction, and autophagy mechanisms. To glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of differential display-PCR, proteome analysis, and COMET assay techniques and shown some differences in the molecular signature profiles induced by exposure to either HDACis...
November 12, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29113067/omics-approaches-for-identifying-physiological-adaptations-to-genome-instability-in-aging
#13
REVIEW
Diletta Edifizi, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage...
November 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29112132/autophagy-roles-in-the-modulation-of-dna-repair-pathways
#14
REVIEW
Luciana R Gomes, Carlos F M Menck, Giovana S Leandro
Autophagy and DNA repair are biological processes vital for cellular homeostasis maintenance and when dysfunctional, they lead to several human disorders including premature aging, neurodegenerative diseases, and cancer. The interchange between these pathways is complex and it may occur in both directions. Autophagy is activated in response to several DNA lesions types and it can regulate different mechanisms and molecules involved in DNA damage response (DDR), such as cell cycle checkpoints, cell death, and DNA repair...
November 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29111769/xpc-deficiency-alters-cigarette-smoke-dna-damage-cell-fate-and-accelerates-emphysema-development
#15
Catherine R Sears, Huaxin Zhou, Matthew J Justice, Amanda J Fisher, Jacob Saliba, Isaac Lamb, Jessica Wicker, Kelly S Schweitzer, Irina Petrache
Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein xeroderma pigmentosum group C (XPC) on CS-induced DNA damage repair and emphysema...
November 7, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29107114/cancer-chemoprevention-via-activation-of-proteostatic-modules
#16
Aimilia Sklirou, Eleni-Dimitra Papanagnou, Nikolas Fokialakis, Ioannis P Trougakos
Proteins carry out the majority of cellular functions and maintain cellular homeodynamics mostly by participating in multimeric assemblies that operate as protein machines. Proteome quality control is thus critical for cellular functionality, and it is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the protein synthesis and trafficking modules, the endoplasmic reticulum unfolded protein response, molecular chaperones, and the two main degradation machineries, namely the ubiquitin proteasome and autophagy lysosome pathways...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29050289/acrolein-induces-mtdna-damages-mitochondrial-fission-and-mitophagy-in-human-lung-cells
#17
Hsiang-Tsui Wang, Jing-Heng Lin, Chun-Hsiang Yang, Chun-Hao Haung, Ching-Wen Weng, Anya Maan-Yuh Lin, Yu-Li Lo, Wei-Shen Chen, Moon-Shong Tang
Acrolein (Acr), a highly reactive unsaturated aldehyde, can cause various lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. We have found that Acr can damage not only genomic DNA but also DNA repair proteins causing repair dysfunction and enhancing cells' mutational susceptibility. While these effects may account for Acr lung carcinogenicity, the mechanisms by which Acr induces lung diseases other than cancer are unclear. In this study, we found that Acr induces damages in mitochondrial DNA (mtDNA), inhibits mitochondrial bioenergetics, and alters mtDNA copy number in human lung epithelial cells and fibroblasts...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29016854/absence-of-rnase-h2-triggers-generation-of-immunogenic-micronuclei-removed-by-autophagy
#18
Kareen Bartsch, Katharina Knittler, Christopher Borowski, Sönke Rudnik, Markus Damme, Konrad Aden, Martina E Spehlmann, Norbert Frey, Paul Saftig, Athena Chalaris, Björn Rabe
Hypomorphic mutations in the DNA repair enzyme RNase H2 cause the neuroinflammatory autoimmune disorder Aicardi-Goutières syndrome (AGS). Endogenous nucleic acids are believed to accumulate in patient cells and instigate pathogenic type I interferon expression. However, the underlying nucleic acid species amassing in the absence of RNase H2 has not been established yet. Here, we report that murine RNase H2 knockout cells accumulated cytosolic DNA aggregates virtually indistinguishable from micronuclei. RNase H2-dependent micronuclei were surrounded by nuclear lamina and most of them contained damaged DNA...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28991411/structural-insights-into-the-nuclear-import-of-the-histone-acetyltransferase-mof-by-importin-%C3%AE-1
#19
Weili Zheng, Rui Wang, Xi Liu, Siyu Tian, Benqiang Yao, Ang Chen, Shikai Jin, Yong Li
The histone acetyltransferase MOF (males-absent-on-the-first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive...
October 9, 2017: Traffic
https://www.readbyqxmd.com/read/28981387/aldh1a1-and-hltf-modulate-the-activity-of-lysosomal-autophagy-inhibitors-in-cancer-cells
#20
Shengfu Piao, Rani Ojha, Vito W Rebecca, Arabinda Samanta, Xiao-Hong Ma, Quentin Mcafee, Michael C Nicastri, Meghan Buckley, Eric Brown, Jeffrey D Winkler, Phyllis A Gimotty, Ravi K Amaravadi
Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines. LAIs are being evaluated in cancer clinical trials, but genetic determinants of sensitivity to LAIs are unknown, making it difficult to predict which tumors would be most susceptible. Here we characterize differentially expressed genes in HCQ-sensitive (-S) and -resistant (-R) cancer cells. Notably, expression of canonical macroautophagy/autophagy genes was not associated with sensitivity to HCQ...
October 5, 2017: Autophagy
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