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https://www.readbyqxmd.com/read/29629140/simultaneous-sensitive-detection-of-multiple-dna-glycosylases-from-lung-cancer-cells-at-the-single-molecule-level
#1
Juan Hu, Ming-Hao Liu, Ying Li, Bo Tang, Chun-Yang Zhang
DNA glycosylases are involved in the base excision repair pathway, and all mammals express multiple DNA glycosylases to maintain genome stability. However, the simultaneous detection of multiple DNA glycosylase still remains a great challenge. Here, we develop a single-molecule detection method for the simultaneous detection of human 8-oxoguanine DNA glycosylase 1 (hOGG1) and human alkyladenine DNA glycosylase (hAAG) on the basis of DNA glycosylase-mediated cleavage of molecular beacons. We designed a Cy3-labeled molecular beacon modified with 8-oxoguanine (8-oxoG) for a hOGG1 assay and a Cy5-labeled molecular beacon modified with deoxyinosine for a hAAG assay...
January 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29575156/the-overexpression-of-tcap1-endonuclease-confers-resistance-to-infective-trypanosoma-cruzi-trypomastigotes-against-oxidative-dna-damage
#2
Lucía Valenzuela, Soía Sepúlveda, Iván Ponce, Norbel Galanti, Gonzalo Cabrera
Trypanosoma cruzi, the causative agent of Chagas' disease survives to DNA damage generated by ROS/RNS inside to their different hosts. In recent eukaryotes, oxidative DNA damage is repaired mainly by the Base Excision Repair (BER) pathway, being essential the apurinic/apyrimidinic endonuclease activity. Using a pTREX-gfp vector, the nucleotide sequence that encodes T. cruzi AP endonuclease TcAP1 (orthologue of human APE1) and a putative TcAP1 dominant negative (TcAP1DN), were transfectedand expressed in T. cruzi epimastigotes...
March 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29565485/clinical-value-of-combined-detection-of-serum-ape1-aabs-and-ceacam-1-in-the-diagnosis-of-colorectal-cancer
#3
W Huajun, F Ying, Z Hongxing, S Weifeng, S Pingyang, H Mingde, L Guoguang
OBJECTIVE: To analyze the clinical value of combined detection of serum APE1-Aabs and CEACAM-1 in pathological diagnosis of colorectal cancer. PATIENTS AND METHODS: From December 2014 to July 2016, 60 patients with colorectal cancer and 50 healthy subjects were enrolled in this study. The levels of APE1-AAbs, CEACAM-1 and CEA in the serum were measured, and the clinical value of each index in the diagnosis of colorectal cancer was analyzed. RESULTS: The level of serum APE1-AAbs in colorectal cancer group was significantly higher than that in healthy control group (p < 0...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29541389/ape1-ref-1-redox-specific-inhibition-decreases-survivin-protein-levels-and-induces-cell-cycle-arrest-in-prostate-cancer-cells
#4
David W McIlwain, Melissa L Fishel, Alexander Boos, Mark R Kelley, Travis J Jerde
A key feature of prostate cancer progression is the induction and activation of survival proteins, including the Inhibitor of Apoptosis (IAP) family member survivin. Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein that is essential in activating oncogenic transcription factors. Because APE1/Ref-1 is expressed and elevated in prostate cancer, we sought to characterize APE1/Ref-1 expression and activity in human prostate cancer cell lines and determine the effect of selective reduction-oxidation (redox) function inhibition on prostate cancer cells in vitro and in vivo ...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29486702/y-box-binding-protein-1-stimulates-abasic-site-cleavage
#5
E E Alemasova, K N Naumenko, N A Moor, O I Lavrik
Apurinic/apyrimidinic (AP) sites are among the most frequent DNA lesions. The first step in the AP site repair involves the magnesium-dependent enzyme AP endonuclease 1 (APE1) that catalyzes hydrolytic cleavage of the DNA phosphodiester bond at the 5' side of the AP site, thereby generating a single-strand DNA break flanked by the 3'-OH and 5'-deoxyribose phosphate (dRP) groups. Increased APE1 activity in cancer cells might correlate with tumor chemoresistance to DNA-damaging treatment. It has been previously shown that the multifunctional oncoprotein Y-box-binding protein 1 (YB-1) interacts with APE1 and inhibits APE1-catalyzed hydrolysis of AP sites in single-stranded DNAs...
December 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29480308/co-administration-of-genistein-with-doxorubicin-loaded-polypeptide-nanoparticles-weakens-the-metastasis-of-malignant-prostate-cancer-by-amplifying-oxidative-damage
#6
Guanyi Wang, Dawei Zhang, Shengcai Yang, Yalin Wang, Zhaohui Tang, Xueqi Fu
Prostate cancer is a typical malignant disease with a high incidence and a poor prognosis. Doxorubicin hydrochloride (DOX·HCl) is one of the most effective agents in the treatment of prostate cancer, but severe side effects and metastasis after its treatment impose restrictions on its application. Herein, a combination of genistein (GEN) and doxorubicin-loaded polypeptide nanoparticles (DOX-NPs) is constructed for the treatment of prostate cancer. The DOX-NPs can reduce the side effects caused by free DOX·HCl and produce a relatively low level of intracellular reactive oxygen species (ROS)-induced oxidative damage, while GEN, an inhibitor of the oxidative DNA repair enzyme apurinic/apyrimidinic endonuclease1 (APE1), can further amplify the ROS-induced oxidative damage by downregulating the intracellular expression of APE1 and reducing oxidative DNA repair in the prostate cancer cells...
February 26, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29475157/the-role-of-the-n-terminal-domain-of-human-apurinic-apyrimidinic-endonuclease-1-ape1-in-dna-glycosylase-stimulation
#7
Olga A Kladova, Milena Bazlekowa-Karaban, Sonia Baconnais, Olivier Piétrement, Alexander A Ishchenko, Bakhyt T Matkarimov, Danila A Iakovlev, Andrey Vasenko, Olga S Fedorova, Eric Le Cam, Barbara Tudek, Nikita A Kuznetsov, Murat Saparbaev
The base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1, a.k.a. APEX1, HAP-1, or Ref-1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3'-blocking sugar moieties at DNA strand breaks. Human 8-oxoguanine-DNA glycosylase (OGG1), methyl-CpG-binding domain 4 (MBD4, a...
February 11, 2018: DNA Repair
https://www.readbyqxmd.com/read/29455351/lead-facilitates-foci-formation-in-a-balb-c-3t3-two-step-cell-transformation-model-role-of-ape1-function
#8
Pablo Hernández-Franco, Martín Silva, Rodrigo Franco, Mahara Valverde, Emilio Rojas
Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 μM induced APE1 mRNA and upregulation of protein expression...
February 17, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29393411/bu-fei-decoction-and-modified-bu-fei-decoction-inhibit-the-growth-of-non-small-cell-lung-cancer-possibly-via-inhibition-of-apurinic-apyrimidinic-endonuclease-1
#9
Shan-Tong Jiang, Shu-Yan Han, Li-Na Pang, Yan-Na Jiao, Xi-Ran He, Ping-Ping Li
Human apurinic/apyrimidinic endonuclease 1 (APE1) is a ubiquitous multifunctional protein, which possesses DNA repair and redox activities. High levels of APE1 are associated with chemo‑ and radioresistance, and poor prognosis in various types of cancer, including non‑small cell lung cancer (NSCLC). Bu‑Fei decoction (BFD) is a traditional Chinese herbal formula, which is believed to supplement Qi, clear away heat and nourish the lungs. BFD and modified Bu‑Fei decoction (MBFD) have been used in China to treat patients with lung cancer...
January 30, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29385574/activity-and-expression-of-candida-glabrata-vacuolar-proteases-in-autophagy-like-conditions
#10
J Luis Cortez-Sánchez, Elías Cortés-Acosta, V Mónica Cueto-Hernández, Elba Reyes-Maldonado, César Hernández-Rodríguez, Lourdes Villa-Tanaca, J Antonio Ibarra
Candida glabrata is an emerging opportunistic pathogen that has intrinsic resistance to azoles antifungals. During infection or while living as a commensal it encounters nutritional stresses such as deficiency of carbon or nitrogen sources. Herein we investigate the expression and activity of PrA, Ape1, Ape3 and CpY vacuolar proteases during these stressful nutrimental conditions. Our findings demonstrate a differential activity profile depending on the addition or lack of carbon, nitrogen or both. Of the four proteases tested, PrA and Ape3 showed a higher activity in the absence of nitrogen...
January 29, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29374164/molecular-snapshots-of-ape1-proofreading-mismatches-and-removing-dna-damage
#11
Amy M Whitaker, Tony S Flynn, Bret D Freudenthal
Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair enzyme which uses a single active site to process DNA damage via two distinct activities: (1) AP-endonuclease and (2) 3' to 5' exonuclease. The AP-endonuclease activity cleaves at AP-sites, while the exonuclease activity excises bulkier 3' mismatches and DNA damage to generate clean DNA ends suitable for downstream repair. Molecular details of the exonuclease reaction and how one active site can accommodate various toxic DNA repair intermediates remains elusive despite being biologically important...
January 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29344998/role-of-ap-endonuclease-ape1-active-site-residues-in-stabilization-of-the-reactant-enzyme-dna-complex
#12
Hossein Batebi, Jovan Dragelj, Petra Imhof
Apurinic/apyrimidinic endonuclease 1 (Ape1) is an important metal-dependent enzyme in the base excision repair mechanism, responsible for the backbone cleavage of abasic DNA through a phosphate hydrolysis reaction. Molecular dynamics simulations of Ape1 complexed to its substrate DNA performed for models containing one or two Mg2+ -ions as cofactor located at different positions show a complex with one metal ion bound on the leaving group site of the scissile phosphate to be the most likely reaction-competent conformation...
January 18, 2018: Proteins
https://www.readbyqxmd.com/read/29233148/dna-repair-protein-ape1-is-involved-in-host-response-during-pneumococcal-meningitis-and-its-expression-can-be-modulated-by-vitamin-b6
#13
Leonam G Coutinho, Ana Helena Sales de Oliveira, Matthias Witwer, Stephen L Leib, Lucymara F Agnez-Lima
BACKGROUND: The production of reactive oxygen species (ROS) during pneumococcal meningitis (PM) leads to severe DNA damage in the neurons and is the major cause of cell death during infection. Hence, the use of antioxidants as adjuvant therapy has been investigated. Previous studies have demonstrated the possible participation of apurinic/apyrimidinic endonuclease (APE1) during PM. The aims of this study were to investigate the APE1 expression in the cortical and hippocampal tissues of infant Wistar rats infected with Streptococcus pneumoniae and its association with cell death and understand the role of vitamin B6 (vitB6) as a protective factor against cell death...
December 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29156789/xrcc1-mediated-the-development-of-cervival-cancer-through-a-novel-sp1-krox-20-swich
#14
Qingtao Meng, Shizhi Wang, Weiyan Tang, Shenshen Wu, Na Gao, Chengcheng Zhang, Xiaoli Cao, Xiaobo Li, Zhengdong Zhang, Michael Aschner, Hua Jin, Yue Huang, Rui Chen
Cervical cancer is the second leading cause of mortality among women. Impairment of the base excision repair (BER) pathway is one of the major causes of the initiation and progression of cervical cancer. However, whether the polymorphisms of the BER pathway components (i.e., HOGG1, XRCC1, ADPRT , and APE1 ) can affect the risk of cervical cancer remains unknown. Herein, we applied a hospital-based case-control study covering two independent cohorts and a subsequent functional assay to determine the roles of the single nucleotide polymorphisms (SNPs) of the BER pathway genes in cervical cancer...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156683/shycd-induces-ape1-ref-1-subcellular-localization-to-regulate-the-p53-apoptosis-signaling-pathway-in-the-prevention-and-treatment-of-acute-on-chronic-liver-failure
#15
Jianxin Diao, Haiye Li, Wei Huang, Wenxiao Ma, Huan Dai, Yawei Liu, Ming Wang, He Yu Hua, Jinying Ou, Xiaomin Sun, Xuegang Sun, Yungao Yang
Background & Aims: San huang yin chi decoction(SHYCD) is derived from the yin chen hao decoction, a well-known and canonical Chinese medicine formula from the "Treatise on Febrile Diseases". Over the past decade, SHYCD has been used to treat and prevent the liver cirrhosis and liver failure. In the present study, we investigated the effects of SHYCD for acute on chronic liver failure(ACLF) and explored its potential mechanism. an ACLF rat model, which induced by carbon tetrachloride (CCl4) combined with D-galactosamine (D-GalN) and lipopolysaccharide(LPS), was used and confirmed by B-ultrasound analysis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-repair-the-genome-and-improve-stroke-recovery
#16
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29122935/in-vivo-measurements-of-interindividual-differences-in-dna-glycosylases-and-ape1-activities
#17
Isaac A Chaim, Zachary D Nagel, Jennifer J Jordan, Patrizia Mazzucato, Le P Ngo, Leona D Samson
The integrity of our DNA is challenged with at least 100,000 lesions per cell on a daily basis. Failure to repair DNA damage efficiently can lead to cancer, immunodeficiency, and neurodegenerative disease. Base excision repair (BER) recognizes and repairs minimally helix-distorting DNA base lesions induced by both endogenous and exogenous DNA damaging agents. Levels of BER-initiating DNA glycosylases can vary between individuals, suggesting that quantitating and understanding interindividual differences in DNA repair capacity (DRC) may enable us to predict and prevent disease in a personalized manner...
November 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29121337/parp1-changes-from-three-dimensional-dna-damage-searching-to-one-dimensional-diffusion-after-auto-parylation-or-in-the-presence-of-ape1
#18
Lili Liu, Muwen Kong, Natalie R Gassman, Bret D Freudenthal, Rajendra Prasad, Stephanie Zhen, Simon C Watkins, Samuel H Wilson, Bennett Van Houten
PARP1-dependent poly-ADP-ribosylation (PARylation) participates in the repair of many forms of DNA damage. Here, we used atomic force microscopy (AFM) and single molecule fluorescence microscopy to examine the interactions of PARP1 with common DNA repair intermediates. AFM volume analysis indicates that PARP1 binds to DNA at nicks, abasic (AP) sites, and ends as a monomer. Single molecule DNA tightrope assays were used to follow the real-time dynamic behavior of PARP1 in the absence and presence of AP endonuclease (APE1) on AP DNA damage arrays...
December 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29119395/comparative-analysis-of-quantitative-parameters-of-expression-of-the-retinoic-acid-nuclear-receptor-rar%C3%AE-gene-and-ape1-yb-1-mdr1-pattern-genes-in-patients-with-newly-detected-multiple-myeloma
#19
N N Kalitin, Yu B Chernykh, I V Buravtsova
The expression of retinoic acid nuclear receptor gene RARα and its relationship with expression of APE1, YB-1, and MDR1 genes was studied in bone marrow aspiration biopsy specimens from 22 patients with newly detected multiple myeloma. The expression of RARα directly correlated with the expression of APE1/YB-1/MDR1 pattern genes. Groups differing by expression of RARα exhibited significant differences in the overall survival of patients; concordant and simultaneous changes in the expression of all genes of the APE1/YB-1/MDR1 pattern suggested the level of RARα gene expression as a potential prognostic factor in the pathogenesis of multiple myeloma...
November 9, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29118522/association-of-leukotrichia-in-vitiligo-and-asp148glu-polymorphism-of-apurinic-apyrimidinic-endonuclease-1
#20
A Fatih Aydin, İkbal Esen Aydıngöz, Semra Doğru-Abbasoğlu, Pervin Vural, Müjdat Uysal
Background: Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. Aim: We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. Materials and Methods: We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo...
October 2017: International Journal of Trichology
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