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https://www.readbyqxmd.com/read/27923991/a-specific-dna-nanoprobe-for-tracking-the-activities-of-human-apurinic-apyrimidinic-endonuclease-1-in-living-cells
#1
Junqiu Zhai, Yibin Liu, Shan Huang, Simin Fang, Meiping Zhao
Human apurinic/apyrimidinic endonuclease/redox effector factor 1 (APE1) is an essential DNA repair protein. Herein, we demonstrate that avidin-oriented abasic site-containing DNA strands (AP-DNA) on the surface of silica coated magnetic nanoparticles (SiMNP) can selectively respond to APE1 while resist the digestion by other nucleases. Mechanism studies have revealed that avidin may serve as an organizer protein and recruit APE1 to the DNA substrates on the nanoparticles via strong and specific interactions...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27908238/thermodynamic-analysis-of-fast-stages-of-specific-lesion-recognition-by-dna-repair-enzymes
#2
REVIEW
N A Kuznetsov, O S Fedorova
The methodology of determination of the thermodynamic parameters of fast stages of recognition and cleavage of DNA substrates is described for the enzymatic processes catalyzed by DNA glycosylases Fpg and hOGG1 and AP endonuclease APE1 during base excision repair (BER) pathway. For this purpose, stopped-flow pre-steady-state kinetic analysis of tryptophan fluorescence intensity changes in proteins and fluorophores in DNA substrates was performed at various temperatures. This approach made it possible to determine the changes of standard Gibbs free energy, enthalpy, and entropy of sequential steps of DNA-substrate binding, as well as activation enthalpy and entropy for the transition complex formation of the catalytic stage...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27893608/ape1-protects-against-mpp-induced-neurotoxicity-through-erk1-2-signaling-in-pc12-cells
#3
Bei Kang, Shengzhi Mu, Qian Yang, Shenglong Guo, Xiaoli Chen, Hena Guo
Oxidative stress, induced by reactive oxygen species (ROS), is an apoptosis activator. Oxidative stress causes dopaminergic neuron loss and plays a pivotal role in the pathogenesis of Parkinson's disease (PD). A recent study showed that apurinic/apyrimidinic endonuclease 1 (Ape1) decreases cytotoxicity and promotes neuron survival under oxidative stress. Furthermore, it has been proven that Ape1 is involved in the pathogenesis of PD. However, little is known about the contribution of Ape1 toward the development of PD...
January 1, 2017: Neuroreport
https://www.readbyqxmd.com/read/27836324/the-major-arabidopsis-thaliana-apurinic-apyrimidinic-endonuclease-arp-is-involved-in-the-plant-nucleotide-incision-repair-pathway
#4
Zhiger Akishev, Sabira Taipakova, Botagoz Joldybayeva, Caroline Zutterling, Izat Smekenov, Alexander A Ishchenko, Dmitry O Zharkov, Amangeldy K Bissenbaev, Murat Saparbaev
Apurinic/apyrimidinic (AP) endonucleases are important DNA repair enzymes involved in two overlapping pathways: DNA glycosylase-initiated base excision (BER) and AP endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, AP endonucleases cleave DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases, whereas in NIR, the same AP endonucleases incise DNA 5' to a wide variety of oxidized bases. The flowering plant Arabidopsis thaliana contains three genes encoding homologues of major human AP endonuclease 1 (APE1): Arp, Ape1L and Ape2...
October 29, 2016: DNA Repair
https://www.readbyqxmd.com/read/27813497/serum-ape1-as-a-predictive-marker-for-platinum-based-chemotherapy-of-non-small-cell-lung-cancer-patients
#5
Shiheng Zhang, Le He, Nan Dai, Wei Guan, Jinlu Shan, Xueqin Yang, Zhaoyang Zhong, Yi Qing, Feng Jin, Chuan Chen, Yuxin Yang, Hongyi Wang, Laura Baugh, Gianluca Tell, David M Wilson Iii, Mengxia Li, Dong Wang
PURPOSE: To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. RESULTS: Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27802207/ape1-overexpression-promotes-the-progression-of-ovarian-cancer-and-serves-as-a-potential-therapeutic-target
#6
Xuemei Wen, Renquan Lu, Suhong Xie, Hui Zheng, Hongling Wang, Yanchun Wang, Jiajun Sun, Xiang Gao, Lin Guo
BACKGROUND: Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that is involved in DNA repair and the redox regulation of transcription factors. Blocking these functions leads to cell-growth inhibition, apoptosis and other effects. Previous studies have demonstrated that high expression levels of the APE1 protein are associated with the progression and chemoresistance of cancers. We hypothesized that APE1 silencing in ovarian cancer cells might have anticancer effects mediated by cell-growth inhibition and an increase in drug-sensitivity...
September 26, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27754271/sy-17-1-dynamic-regulation-of-redox-regulating-factor-ape1-ref-1-on-the-oxidative-stress-and-vascular-inflammation
#7
Byeong Hwa Jeon
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. Heterozygous APE1/Ref-1 mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27748797/reduced-apurinic-apyrimidinic-endonuclease-activity-enhances-the-antitumor-activity-of-oxymatrine-in-lung-cancer-cells
#8
Zhiqiang Wang, Wenya Xu, Ziying Lin, Chunyan Li, Yahong Wang, Lawei Yang, Gang Liu
Lung cancer is the leading cause of cancer-related deaths worldwide and is associated with a very poor outcome. Oxymatrine exerts antitumor effects by inducing apoptosis and inhibiting the proliferation of different cancer cells; however, the anticancer effects and mechanism of action of oxymatrine have not been evaluated sufficiently in human lung cancer cells. Thus, the present study aimed to investigate the anticancer effects of oxymatrine in human lung cancer cells and identify the molecular mechanisms underlying these effects...
October 14, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27729279/a-protective-mechanism-of-visible-red-light-in-normal-human-dermal-fibroblasts-enhancement-of-gadd45a-mediated-dna-repair-activity
#9
Yeo Jin Kim, Hyoung-June Kim, Hye Lim Kim, Hyo Jeong Kim, Hyun Soo Kim, Tae Ryong Lee, Dong Wook Shin, Young Rok Seo
The phototherapeutic effects of visible red light on skin have been extensively investigated, but the underlying biological mechanisms remain poorly understood. We aimed to elucidate the protective mechanism of visible red light in terms of DNA repair of UV-induced oxidative damage in normal human dermal fibroblasts. The protective effect of visible red light on UV-induced DNA damage was identified by several assays in both two-dimensional and three-dimensional cell culture systems. With regard to the protective mechanism of visible red light, our data showed alterations in base excision repair (BER) mediated by growth arrest and DNA damage inducible, alpha (GADD45A)...
October 8, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27722620/a-kinetic-mechanism-of-repair-of-dna-containing-%C3%AE-anomeric-deoxyadenosine-by-human-apurinic-apyrimidinic-endonuclease-1
#10
N A Timofeyeva, O S Fedorova
α-Anomers of 2'-deoxyadenosine (αdA) are major products of deoxyadenosine damage when DNA is γ-irradiated under anoxic conditions. Such lesions are a threat to genomic stability and are known to be processed by human apurinic/apyrimidinic endonuclease 1 (APE1). The aim of this study was to determine whether the α-anomeric structure enhances enzyme recognition. For this purpose, we analyzed the kinetic mechanism of αdA conversion by APE1 using a stopped-flow fluorescence technique. Our data reveals that the initial formation of the complex of APE1 with an αdA-containing substrate is followed by at least three conformational transitions in this complex that correspond to the induced fit leading to the formation of a catalytically competent complex...
September 22, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27707956/dynamics-of-base-excision-repair-at-the-maternal-fetal-interface-in-pregnancies-complicated-by-preeclampsia
#11
Serkalem Tadesse, Nicholas G Norwitz, Seth Guller, Felice Arcuri, Paolo Toti, Errol R Norwitz, Dawit Kidane
Preeclampsia (PE) (gestational proteinuric hypertension) is the leading cause of maternal and perinatal mortality worldwide. Although placental endothelial dysfunction and oxidative stress are known to contribute to PE, the exact pathological basis for this disorder remains unclear. Previously, we demonstrated that DNA damage at the maternal-fetal interface is more common in the placentas of women with PE than normotensive controls. In this study, we utilized an in vivo comparative study, including 20 preeclamptic women and 8 healthy control subjects, and an in vitro hypoxia/reperfusion model to mimic the effects of oxidative stress at the maternal-fetal interface...
October 5, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27698937/activation-of-glp-1-receptor-enhances-neuronal-base-excision-repair-via-pi3k-akt-induced-expression-of-apurinic-apyrimidinic-endonuclease-1
#12
Jenq-Lin Yang, Wei-Yu Chen, Yin-Ping Chen, Chao-Ying Kuo, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage...
2016: Theranostics
https://www.readbyqxmd.com/read/27682167/ap-endonuclease-1-as-a-key-enzyme-in-repair-of-apurinic-apyrimidinic-sites
#13
REVIEW
N S Dyrkheeva, N A Lebedeva, O I Lavrik
Human apurinic/apyrimidinic endonuclease 1 (APE1) is one of the key participants in the DNA base excision repair system. APE1 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. APE1 exhibits 3'-phosphodiesterase, 3'-5'-exonuclease, and 3'-phosphatase activities. APE1 was also identified as a redox factor (Ref-1). In this review, data on the role of APE1 in the DNA repair process and in other metabolic processes occurring in cells are analyzed as well as the interaction of this enzyme with DNA and other proteins participating in the repair system...
September 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27643268/sy-17-1-dynamic-regulation-of-redox-regulating-factor-ape1-ref-1-on-the-oxidative-stress-and-vascular-inflammation
#14
Byeong Hwa Jeon
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. Heterozygous APE1/Ref-1 mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27637330/apurinic-apyrimidinic-endonuclease-1-redox-factor-1-ape1-ref-1-modulates-antigen-presenting-cell-mediated-t-helper-cell-type-1-responses
#15
Nasrin Akhter, Yuji Takeda, Hidetoshi Nara, Akemi Araki, Naoto Ishii, Naoki Asao, Hironobu Asao
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) is a multifunctional protein possessing DNA repair, redox control, and transcriptional regulatory activities. Although Ape1/Ref-1 plays multiple roles in the immune system, its functions in helper T (Th) cell activation and differentiation are largely unknown. In this study, the function of Ape1/Ref-1 in Th cell activation was analyzed using an Ape1/Ref-1 redox-specific inhibitor, E3330. When splenocytes from OT-II mice, which are ovalbumin (OVA)-specific T-cell receptor transgenic mice, were activated with OVA in the presence of E3330, the induction of IFN-γ-producing OT-II T cells was significantly increased...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27620821/-what-makes-some-rats-live-so-long-the-mitochondrial-contribution-to-longevity-through-balance-of-mitochondrial-dynamics-and-mtdna-content
#16
Anna Picca, Vito Pesce, Giuseppe Sirago, Flavio Fracasso, Christiaan Leeuwenburgh, Angela Maria Serena Lezza
Extremely interesting for aging research are those individuals able to reach older ages still with functions similar to those of younger counterparts. We examined liver samples from ad libitum-fed old (28-month-old, AL-28) and ad libitum-fed very old (32-month-old, AL-32) rats for a number of markers, relevant for mitochondrial functionality and mitochondrial DNA (mtDNA) content. As for the mtDNA content and the protein amounts of the citrate synthase and the antioxidant peroxiredoxin III there were no significant changes in the AL-32 animals...
September 13, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27614295/next-generation-electron-microscopy-in-autophagy-research
#17
James H Hurley, Eva Nogales
Autophagy is the process whereby cytosol, organelles, and inclusions are taken up in a double-membrane vesicle known as the autophagosome, and transported to the lysosome for destruction and recycling. Electron microscopy (EM) led to the discovery of autophagy in the 1950s and has been a central part of its characterization ever since. New capabilities in single particle EM studies of the autophagy machinery are beginning to provide exciting insights into the mechanisms of autophagosome initiation, growth, and substrate targeting...
September 7, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27612654/in-vitro-effects-of-photodynamic-therapyinduced-by-chloroaluminum-phthalocyanine-nanoemulsion
#18
Leonardo Pereira Franch, Camila F Amantino, Maryanne T Melo, Ana Paula de Lima Montaldi, Fernando L Primo, Antonio Claudio Tedesco
BACKGROUND: The photodynamic therapy (PDT) has been used to treat cancer mainly by inducing oxidative stress. Our aim was to evaluate the effect of PDT and its combination with methoxyamine (MX), a blocker of base excision repair (BER), in cells expressing high levels of the APE1 protein, which is involved in cell oxidative damage response. METHODS: The HeLa and A549 cells were treated for 3h with chloroaluminum phthalocyanine incorporated into a well-designed nanoemulsion (ClAlPc/NE); and then irradiated by visible light (@670nm) with doses of 0...
September 6, 2016: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/27612215/repair-rate-of-clustered-abasic-dna-lesions-by-human-endonuclease-molecular-bases-of-sequence-specificity
#19
Hugo Gattuso, Elodie Durand, Emmanuelle Bignon, Christophe Morell, Alexandros G Georgakilas, Elise Dumont, Christophe Chipot, François Dehez, Antonio Monari
In the present contribution, the interaction between damaged DNA and repair enzymes is examined by means of molecular dynamics simulations. More specifically, we consider clustered abasic DNA lesions processed by the primary human apurinic/apyrimidinic (AP) endonuclease, APE1. Our results show that, in stark contrast with the corresponding bacterial endonucleases, human APE1 imposes strong geometrical constraints on the DNA duplex. As a consequence, the level of recognition and, hence, the repair rate is higher...
October 6, 2016: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/27608656/identification-and-characterization-of-new-chemical-entities-targeting-apurinic-apyrimidinic-endonuclease-1-for-the-prevention-of-chemotherapy-induced-peripheral-neuropathy
#20
Mark R Kelley, James H Wikel, Chunlu Guo, Karen E Pollok, Barbara J Bailey, Randy Wireman, Melissa L Fishel, Michael R Vasko
Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially debilitating side effect of a number of chemotherapeutic agents. There are currently no U.S. Food and Drug Administration-approved interventions or prevention strategies for CIPN. Although the cellular mechanisms mediating CIPN remain to be determined, several lines of evidence support the notion that DNA damage caused by anticancer therapies could contribute to the neuropathy. DNA damage in sensory neurons after chemotherapy correlates with symptoms of CIPN...
November 2016: Journal of Pharmacology and Experimental Therapeutics
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