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https://www.readbyqxmd.com/read/28523411/apurinic-apyrimidinic-endonuclease-1-ape1-is-overexpressed-in-malignant-transformation-of-salivary-gland-pleomorphic-adenoma
#1
Leorik Pereira Silva, Thalita Santana, Bruno Tavares Sedassari, Suzana Machado de Sousa, Ana Paula Veras Sobral, Roseana de Almeida Freitas, Carlos Augusto Galvão Barboza, Lélia Batista de Souza
DNA repair systems play a critical role in protecting the human genome against cumulative damage. The apurinic/apyrimidinic endonuclease 1 is a protein involved in DNA base excision repair and its expression still needs to be investigated in salivary gland tumors. The objective of this study is to analyze the immunoexpression of apurinic/apyrimidinic endonuclease 1 in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of the salivary glands. A total of 33 pleomorphic adenomas and 16 carcinomas ex pleomorphic adenomas of the salivary glands underwent immunohistochemical study by the polymeric biotin-free technique...
May 18, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28520216/evaluation-of-prediction-of-polymorphisms-of-dna-repair-genes-on-the-efficacy-of-platinum-based-chemotherapy-in-patients-with-non-small-cell-lung-cancer-a-network-meta-analysis
#2
Bao-Hong Fu, Xiao-Lin Yu, Qiang Zhang, Xin-Long Huo, Li-Jie Liu, Xin Li, Li-Xin Dong
This network meta-analysis (NMA) was conducted to compare the predictive value of 14 SNPs in 8 DNA repair genes on the efficacy of platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC). These included ERCC1 (rs11615, rs3212986, rs3212948), XRCC1 (rs25487, rs25489, rs1799782), XPD (rs13181, rs1799793), XPG (rs1047768, rs17655), XPA (rs1800975), XRCC3 (rs861539), APE1 (rs3136820) and RRM1 (rs1042858). The PubMed and Cochrane library databases were reviewed from their inception to February 2017 and studies which met our inclusion criteria were included in our investigation...
May 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28501783/silencing-of-dna-repair-sensitizes-pediatric-brain-tumor-cells-to-%C3%AE-irradiation-using-gold-nanoparticles
#3
Zuliang Liu, Huiru Yan, Hongsha Li
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor resistance to radiation therapy...
April 27, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28481984/the-dna-damage-response-ddr-is-induced-by-the-c9orf72-repeat-expansion-in-amyotrophic-lateral-sclerosis
#4
Manal A Farg, Anna Konopka, Kai Ying Soo, Daisuke Ito, Julie D Atkin
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease affecting motor neurons. Hexanucleotide (GGGGCC) repeat expansions in a non-coding region of C9orf72 are the major cause of familial ALS and frontotemporal dementia (FTD) worldwide. The C9orf72 repeat expansion undergoes repeat-associated non-ATG (RAN) translation to produce five dipeptide repeat proteins (DRPs), including poly(GR) and poly(PR). Whilst it remains unclear how mutations in C9orf72 lead to neurodegeneration in ALS/FTD, dysfunction to the nucleolus and R loop formation are implicated as pathogenic mechanisms...
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28467610/apurinic-apyrimidinic-endonuclease-1-ape1-ref-1-overexpression-is-an-independent-prognostic-marker-in-prostate-cancer-without-tmprss2-erg-fusion
#5
Manuela Juhnke, Asmus Heumann, Viktoria Chirico, Doris Höflmayer, Anne Menz, Andrea Hinsch, Claudia Hube-Magg, Martina Kluth, Dagmar S Lang, Christina Möller-Koop, Guido Sauter, Ronald Simon, Burkhard Beyer, Raisa Pompe, Imke Thederan, Thorsten Schlomm, Andreas M Luebke
Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9,763 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. The comparison with normal prostate tissue revealed an upregulation of APE1 in cancer samples. APE1 immunostaining was considered weak in 20...
May 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28465493/reduction-oxidation-pathways-involved-in-cancer-development-a-systematic-review-of-literature-reviews
#6
REVIEW
Xīn Gào, Ben Schöttker
Oxidative stress results from an imbalance of the reactive oxygen species/reactive nitrogen species (ROS/RNS) production and the oxidants defense system. Extensive research during the last decades has revealed that oxidative stress can mediate cancer initiation and development by leading not only to molecular damage but also to a disruption of reduction-oxidation (redox) signaling. In order to provide a global overview of the redox signaling pathways, which play a role in cancer formation, we conducted a systematic literature search in PubMed and ISI Web of Science and identified 185 relevant reviews published in the last 10 years...
April 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446640/ref-1-ape1-as-transcriptional-regulator-and-novel-therapeutic-target-in-pediatric-t-cell-leukemia
#7
Jixin Ding, Melissa L Fishel, April M Reed, Erin McAdams, Magdalena Czader, Angelo A Cardoso, Mark R Kelley
The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28404743/nuclear-complex-of-glyceraldehyde-3-phosphate-dehydrogenase-and-dna-repair-enzyme-apurinic-apyrimidinic-endonuclease-i-protect-smooth-muscle-cells-against-oxidant-induced-cell-death
#8
Xuwei Hou, Patricia Snarski, Yusuke Higashi, Tadashi Yoshida, Alexander Jurkevich, Patrick Delafontaine, Sergiy Sukhanov
Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMC that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis...
April 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28396513/common-polymorphisms-of-the-hogg1-ape1and-xrcc1genescorrelate-with-the-susceptibility-and-clinicopathological-features-of-primary-angle-closure-glaucoma
#9
Kun Zeng, Bo Zhong, Min Fang, Xiao-Li Shen, Li-Na Huang
This case study aims to elucidate the correlation between the hOGG1 , APE1 and XRCC1 gene polymorphisms to the susceptibility and clinicopathological features of primary angle-closure glaucoma (PACG) in a Chinese Han population. Blood samples were obtained from 258 PACG patients (case group) and 272 healthy volunteers (control group). Polymerase chain reaction with sequence specific primer (PCR-SSP) was used to determine the allele frequencies and genotype distributions of the hOGG1 , APE1 and XRCC1 genes. The risk factors of PACG were determined using logistic regression analysis...
April 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28380040/an-ape1-inhibitor-reveals-critical-roles-of-the-redox-function-of-ape1-in-kshv-replication-and-pathogenic-phenotypes
#10
Canrong Zhong, Mengyang Xu, Yan Wang, Jun Xu, Yan Yuan
APE1 is a multifunctional protein with a DNA base excision repair function in its C-terminal domain and a redox activity in its N-terminal domain. The redox function of APE1 converts certain transcription factors from inactive oxidized to active reduced forms. Given that among the APE1-regulated transcription factors many are critical for KSHV replication and pathogenesis, we investigated whether inhibition of APE1 redox function blocks KSHV replication and Kaposi's sarcoma (KS) phenotypes. With an shRNA-mediated silencing approach and a known APE-1 redox inhibitor, we demonstrated that APE1 redox function is indeed required for KSHV replication as well as KSHV-induced angiogenesis, validating APE1 as a therapeutic target for KSHV-associated diseases...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28360037/mitochondrial-dna-integrity-is-maintained-by-ape1-in-carcinogen-induced-colorectal-cancer
#11
Joan Ballista-Hernandez, Magaly Martinez-Ferrer, Roman Velez, Consuelo Climent, Maria M Sanchez-Vazquez, Ceidy Torres, Adlin Rodriguez-Munoz, Sylvette Ayala-Pena, Carlos A Torres-Ramos
Changes in mitochondrial DNA (mtDNA) integrity have been reported in many cancers, however, the contribution of mtDNA integrity to tumorigenesis is not well understood. We used a transgenic mouse model that is haploinsufficient for the apurinic/apyrimidinic endonuclease 1 (Apex1+/-) gene, which encodes the base excision repair (BER) enzyme APE1, to determine its role in protecting mtDNA from the effects of azoxymethane (AOM), a carcinogen used to induce colorectal cancer (CRC). Repair kinetics of AOM-induced mtDNA damage was evaluated using quantitative PCR after a single AOM dose and a significant induction in mtDNA lesions in colonic crypts from both wild type (WT) and Apex1+/-animals were observed...
March 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28345889/ap-endonuclease-1-accelerates-turnover-of-human-8-oxoguanine-dna-glycosylase-by-preventing-retrograde-binding-to-the-abasic-site-product
#12
Alexandre Esadze, Gaddiel Rodriguez, Shannen L Cravens, James T Stivers
A major product of oxidative DNA damage is 8-oxoguanine. In humans, 8-oxoguanine DNA glycosylase (hOGG1) facilitates removal of these lesions, producing an abasic (AP) site in the DNA that is subsequently incised by AP-endonuclease 1 (APE1). APE1 stimulates turnover of several glycosylases by accelerating rate-limiting product release. However, there have been conflicting accounts of whether hOGG1 follows a similar mechanism. In pre-steady-state kinetic measurements, we found that addition of APE1 had no effect on the rapid burst phase of 8-oxoguanine excision by hOGG1 but accelerated steady-state turnover (kcat) by ∼10-fold...
April 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/28303665/the-ape1-redox-inhibitor-e3330-reduces-collective-cell-migration-of-human-breast-cancer-cells-and-decreases-chemoinvasion-and-colony-formation-when-combined-with-docetaxel
#13
Patrícia S Guerreiro, Eduardo Corvacho, João G Costa, Nuno Saraiva, Ana Sofia Fernandes, Matilde Castro, Joana P Miranda, Nuno G Oliveira
The human apurinic/apyrimidinic endonuclease 1 (APE1) is an ubiquitous multifunctional DNA repair enzyme and a redox signalling protein. Our work addressed the inhibition of APE1 redox function using E3330, as single agent or in combination with docetaxel (DTX), in human breast cancer MDA-MB-231 cells. E3330 decreased the colony formation of DTX-treated cells. In addition, E3330 alone significantly reduced the collective cell migration as assessed by the wound healing assay whereas the combined treatment decreased chemoinvasion...
March 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28242328/mitochondrial-transcription-factor-a-tfam-rs1937-and-ap-endonuclease-1-ape1-rs1130409-alleles-are-associated-with-reduced-cognitive-performance
#14
Meryl S Lillenes, Mari Støen, Clara-Cecilie Günther, Per Selnes, Vidar T V Stenset, Thomas Espeseth, Ivar Reinvang, Tormod Fladby, Tone Tønjum
Mitochondrial dysfunction and DNA damage is intimately connected to ageing and neurodegeneration, including Alzheimer's disease (AD). A particular culprit in this context is oxidative stress, which is a result of increased reactive oxygen species (ROS) due to hyperactive or dysfunctional mitochondria and/or reduced DNA repair capacity. Base excision repair (BER) is the major pathway for repairing oxidative damage events in chromosomal and mitochondrial DNA. Defects in BER have been detected in ageing and neurodegeneration...
February 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28222524/a-combination-of-resveratrol-and-curcumin-is-effective-against-aluminum-chloride-induced-neuroinflammation-in-rats
#15
Amira Zaky, Ahmad Bassiouny, Mahitab Farghaly, Bassma M El-Sabaa
BACKGROUND: Experimental studies have demonstrated that aluminum is an environmental toxin that induces neuroinflammation and the development of Alzheimer's disease. OBJECTIVE: In this report, we investigated the beneficial effect of a combination of resveratrol and curcumin to reduce aluminum-induced neuroinflammation. METHOD: We employed both an in vivo model of aluminum-induced neuroinflammation and an in vitro aluminum stimulated cultured PC-12 cells...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28181292/tumor-associated-ape1-variant-exhibits-reduced-complementation-efficiency-but-does-not-promote-cancer-cell-phenotypes
#16
Jennifer L Illuzzi, Daniel R McNeill, Paul Bastian, Boris Brenerman, Robert Wersto, Helen R Russell, Fred Bunz, Peter J McKinnon, Kevin G Becker, David M Wilson
Base excision repair (BER) is the major pathway for coping with most forms of endogenous DNA damage, and defects in the process have been associated with carcinogenesis. Apurinic/apyrimidinic endonuclease 1 (APE1) is a central participant in BER, functioning as a critical endonuclease in the processing of noncoding abasic sites in DNA. Evidence has suggested that APE1 missense mutants, as well as altered expression or localization of the protein, can contribute to disease manifestation. We report herein that the tumor-associated APE1 variant, R237C, shows reduced complementation efficiency of the methyl methanesulfonate hypersensitivity and impaired cell growth exhibited by APE1-deficient mouse embryonic fibroblasts...
March 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28161249/inhibitors-of-nuclease-and-redox-activity-of-apurinic-apyrimidinic-endonuclease-1-redox-effector-factor-1-ape1-ref-1
#17
REVIEW
Sergey S Laev, Nariman F Salakhutdinov, Olga I Lavrik
Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA-binding activity of certain transcription factors through its redox function. Studies have indicated a role for APE1/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs...
January 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28143930/oxidative-dna-damage-is-epigenetic-by-regulating-gene-transcription-via-base-excision-repair
#18
Aaron M Fleming, Yun Ding, Cynthia J Burrows
Reactive oxygen species (ROS) have emerged as important cellular-signaling agents for cellular survival. Herein, we demonstrate that ROS-mediated oxidation of DNA to yield 8-oxo-7,8-dihydroguanine (OG) in gene promoters is a signaling agent for gene activation. Enhanced gene expression occurs when OG is formed in guanine-rich, potential G-quadruplex-forming sequences (PQS) in promoter-coding strands, initiating base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1), yielding an abasic site (AP). The AP enables melting of the duplex to unmask the PQS, adopting a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of vascular endothelial growth factor (VEGF) or endonuclease III-like protein 1 (NTHL1) genes...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28139742/polymorphism-of-apyrimidinic-dna-structures-in-the-nucleosome
#19
Akihisa Osakabe, Yasuhiro Arimura, Syota Matsumoto, Naoki Horikoshi, Kaoru Sugasawa, Hitoshi Kurumizaka
Huge amounts (>10,000/day) of apurinic/apyrimidinic (AP) sites are produced in genomes, but their structures in chromatin remain undetermined. We determined the crystal structure of the nucleosome containing AP-site analogs at two symmetric sites, which revealed structural polymorphism: one forms an inchworm configuration without an empty space at the AP site, and the other forms a B-form-like structure with an empty space and the orphan base. This unexpected inchworm configuration of the AP site is important to understand the AP DNA repair mechanism, because it may not be recognized by the major AP-binding protein, APE1, during the base excision repair process...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28110804/differential-role-of-base-excision-repair-proteins-in-mediating-cisplatin-cytotoxicity
#20
Akshada Sawant, Ashley M Floyd, Mohan Dangeti, Wen Lei, Robert W Sobol, Steve M Patrick
Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL...
March 2017: DNA Repair
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