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Dna repair and autophagy

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https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#1
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28292950/papers-of-note-in-nature543-7644
#2
Annalisa M VanHook
This week's articles highlight the role of autophagy in maintaining stem cells and a new player in the repair of double-strand DNA breaks.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28288132/census-and-evaluation-of-p53-target-genes
#3
REVIEW
M Fischer
The tumor suppressor p53 functions primarily as a transcription factor. Mutation of the TP53 gene alters its response pathway, and is central to the development of many cancers. The discovery of a large number of p53 target genes, which confer p53's tumor suppressor function, has led to increasingly complex models of p53 function. Recent meta-analysis approaches, however, are simplifying our understanding of how p53 functions as a transcription factor. In the survey presented here, a total set of 3661 direct p53 target genes is identified that comprise 3509 potential targets from 13 high-throughput studies, and 346 target genes from individual gene analyses...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28283188/targeted-cytoplasmic-irradiation-and-autophagy
#4
Jinhua Wu, Bo Zhang, Yen-Ruh Wuu, Mercy M Davidson, Tom K Hei
The effect of ionizing irradiation on cytoplasmic organelles is often underestimated because the general dogma considers direct DNA damage in the nuclei to be the primary cause of radiation induced toxicity. Using a precision microbeam irradiator, we examined the changes in mitochondrial dynamics and functions triggered by targeted cytoplasmic irradiation with α-particles. Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to activation of autophagy, which degraded dysfunctional mitochondria in order to maintain cellular energy homeostasis...
March 1, 2017: Mutation Research
https://www.readbyqxmd.com/read/28265788/a-review-of-supervised-machine-learning-applied-to-ageing-research
#5
REVIEW
Fabio Fabris, João Pedro de Magalhães, Alex A Freitas
Broadly speaking, supervised machine learning is the computational task of learning correlations between variables in annotated data (the training set), and using this information to create a predictive model capable of inferring annotations for new data, whose annotations are not known. Ageing is a complex process that affects nearly all animal species. This process can be studied at several levels of abstraction, in different organisms and with different objectives in mind. Not surprisingly, the diversity of the supervised machine learning algorithms applied to answer biological questions reflects the complexities of the underlying ageing processes being studied...
April 2017: Biogerontology
https://www.readbyqxmd.com/read/28254675/from-ancient-herb-to-modern-drug-artemisia-annua-and-artemisinin-for-cancer-therapy
#6
REVIEW
Thomas Efferth
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28224747/why-do-lactobacilli-dominate-the-human-vaginal-microbiota
#7
REVIEW
S S Witkin, I M Linhares
Lactobacilli are the most abundant vaginal bacteria in women. They inhibit binding of other bacteria to epithelial cells and produce lactic acid that kills or inhibits the growth of many other bacteria. Lactic acid blocks histone deacetylases, thereby enhancing gene transcription and DNA repair. Lactic acid induces autophagy in epithelial cells to degrade intracellular microorganisms and promote homeostasis. Lactobacilli are tolerated by vaginal epithelial cells and inhibit induction of pro-inflammatory cytokines...
March 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#8
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28154131/a-pathway-of-targeted-autophagy-is-induced-by-dna-damage-in-budding-yeast
#9
Vinay V Eapen, David P Waterman, Amélie Bernard, Nathan Schiffmann, Enrich Sayas, Roarke Kamber, Brenda Lemos, Gonen Memisoglu, Jessie Ang, Allison Mazella, Silvia G Chuartzman, Robbie J Loewith, Maya Schuldiner, Vladimir Denic, Daniel J Klionsky, James E Haber
Autophagy plays a central role in the DNA damage response (DDR) by controlling the levels of various DNA repair and checkpoint proteins; however, how the DDR communicates with the autophagy pathway remains unknown. Using budding yeast, we demonstrate that global genotoxic damage or even a single unrepaired double-strand break (DSB) initiates a previously undescribed and selective pathway of autophagy that we term genotoxin-induced targeted autophagy (GTA). GTA requires the action primarily of Mec1/ATR and Rad53/CHEK2 checkpoint kinases, in part via transcriptional up-regulation of central autophagy proteins...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28140789/p53-and-rad9-the-dna-damage-response-and-regulation-of-transcription-networks
#10
Howard B Lieberman, Sunil K Panigrahi, Kevin M Hopkins, Li Wang, Constantinos G Broustas
The way cells respond to DNA damage is important since inefficient repair or misrepair of lesions can have deleterious consequences, including mutation, genomic instability, neurodegenerative disorders, premature aging, cancer or death. Whether damage occurs spontaneously as a byproduct of normal metabolic processes, or after exposure to exogenous agents, cells muster a coordinated, complex DNA damage response (DDR) to mitigate potential harmful effects. A variety of activities are involved to promote cell survival, and include DNA repair, DNA damage tolerance, as well as transient cell cycle arrest to provide time for repair before entry into critical cell cycle phases, an event that could be lethal if traversal occurs while damage is present...
January 31, 2017: Radiation Research
https://www.readbyqxmd.com/read/28123308/strategies-of-temozolomide-in-future-glioblastoma-treatment
#11
REVIEW
Chooi Yeng Lee
Glioblastoma multiforme (GBM) may be one of the most challenging brain tumors to treat, as patients generally do not live more than 2 years. This review aimed to give a timely review of potential future treatments for GBM by looking at the latest strategies, involving mainly the use of temozolomide (TMZ). Although these studies were carried out either in vitro or in rodents, the findings collectively suggested that we are moving toward developing a more efficacious therapy for GBM patients. Nanoparticles preparation was, by far, the most extensively studied strategy for targeted brain delivery...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28104298/kr%C3%A3-pple-like-factor-10-regulates-radio-sensitivity-of-pancreatic-cancer-via-uv-radiation-resistance-associated-gene
#12
Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
BACKGROUND AND PURPOSE: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. MATERIALS AND METHODS: Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28098843/perm-hypothesis-the-fundamental-machinery-able-to-elucidate-the-role-of-xenobiotics-and-hormesis-in-cell-survival-and-homeostasis
#13
REVIEW
Salvatore Chirumbolo, Geir Bjørklund
In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response...
January 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098348/impact-of-lysosomal-storage-disorders-on-biology-of-mesenchymal-stem-cells-evidences-from-in-vitro-silencing-of-glucocerebrosidase-gba-and-alpha-galactosidase-a-gla-enzymes
#14
Tiziana Squillaro, Antonucci Ivana, Nicola Alessio, Anna Esposito, Marilena Cipollaro, Marina Melone, Gianfranco Peluso, Liborio Stuppia, Umberto Galderisi
Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28066797/mitochondrial-dysfunction-activates-the-ampk-signaling-and-autophagy-to-promote-cell-survival
#15
Baozhong Zhao, Lei Qiang, Joy Joseph, Balaraman Kalyanaraman, Benoit Viollet, Yu-Ying He
Autophagy is a cellular self-eating process essential for stress response and maintaining tissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles. Here, we show that cells with defective mitochondria induce autophagy to promote cell survival through activating the AMPK pathway. Loss of mitochondrial complex III protein cytochrome b activates the AMPK signaling and induced autophagy. Inhibiting mitochondria energetics by mitochondria-targeted agents activates the AMPK signaling and induced autophagy...
March 2016: Genes & Diseases
https://www.readbyqxmd.com/read/28042876/the-chk1-inhibitor-mk-8776-increases-the-radiosensitivity-of-human-triple-negative-breast-cancer-by-inhibiting-autophagy
#16
Zhi-Rui Zhou, Zhao-Zhi Yang, Shao-Jia Wang, Li Zhang, Ju-Rui Luo, Yan Feng, Xiao-Li Yu, Xing-Xing Chen, Xiao-Mao Guo
MK-8776 is a recently described inhibitor that is highly selective for checkpoint kinase 1 (Chk1), which can weaken the DNA repair capacity in cancer cells to achieve chemo-sensitization. A number of studies show that MK-8776 enhances the cytotoxicity of hydroxyurea and gemcitabine without increasing normal tissue toxicities. Thus far, there is no evidence that MK-8776 can be used as a radiotherapy sensitization agent. In this study, we investigated the effects of MK-8776 on the radiosensitivity of 3 human triple-negative breast cancer (TNBC) cell lines MDA-MB-231, BT-549 and CAL-51...
January 2, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28026821/the-role-of-survivin-in-the-diagnosis-and-therapy-of-gynaecological-cancers
#17
Marta Denel-Bobrowska, Agnieszka Marczak
Survivin is a member of the family of apoptosis inhibitors. It regulates several essential cellular processes, i.e. it inhibits apoptosis and promotes cell proliferation, DNA repair and autophagy. Survivin is responsible for development of the cell's resistance to chemotherapy and radiotherapy. Overexpression of survivin generally correlates with poor prognosis. Its presence has been detected in most types of human tumours. Currently much attention is paid to the possibilities of using this protein as a diagnostic marker of cancer or a prognostic factor...
December 8, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28011061/repair-reuse-recycle-the-expanding-role-of-autophagy-in-genome-maintenance
#18
REVIEW
Graeme Hewitt, Viktor I Korolchuk
(Macro)Autophagy is a catabolic pathway that delivers excess, aggregated, or damaged proteins and organelles to lysosomes for degradation. Autophagy is activated in response to numerous cellular stressors such as increased levels of reactive oxygen species (ROS) and low levels of cellular nutrients as well as DNA damage. Although autophagy occurs in the cytoplasm, its inhibition leads to accumulation of DNA damage and genomic instability. In the past few years, our understanding of the interplay between autophagy and genomic stability has greatly increased...
December 20, 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27997746/autophagy-an-adaptive-physiological-countermeasure-to-cellular-senescence-and-ischaemia-reperfusion-associated-cardiac-arrhythmias
#19
REVIEW
Istvan Lekli, David Donald Haines, Gyorgy Balla, Arpad Tosaki
Oxidative stress placed on tissues that involved in pathogenesis of a disease activates compensatory metabolic changes, such as DNA damage repair that in turn causes intracellular accumulation of detritus and 'proteotoxic stress', leading to emergence of 'senescent' cellular phenotypes, which express high levels of inflammatory mediators, resulting in degradation of tissue function. Proteotoxic stress resulting from hyperactive inflammation following reperfusion of ischaemic tissue causes accumulation of proteinaceous debris in cells of the heart in ways that cause potentially fatal arrhythmias, in particular ventricular fibrillation (VF)...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#20
REVIEW
Mark Preciados, Changwon Yoo, Deodutta Roy
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese...
December 13, 2016: International Journal of Molecular Sciences
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