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https://www.readbyqxmd.com/read/28222524/a-combination-of-resveratrol-and-curcumin-is-effective-against-aluminum-chloride-induced-neuroinflammation-in-rats
#1
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
#2
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-%C3%A2
#3
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
#4
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...
January 31, 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
#5
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
#6
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...
January 11, 2017: DNA Repair
https://www.readbyqxmd.com/read/28098985/hmgb1-stimulates-activity-of-polymerase-%C3%AE-on-nucleosome-substrates
#7
Angela Balliano, Fanfan Hao, Catherine Njeri, Lata Balakrishnan, Jeffrey J Hayes
The process of base excision repair (BER) recognizes and repairs small lesions or inappropriate bases on DNA through either a short-patch or long-patch pathway. The enzymes involved in BER have been well-characterized on DNA substrates, and, somewhat surprisingly, many of these enzymes, including several DNA glycosylases, AP endonuclease (APE), FEN1 endonuclease, and DNA ligases, have been shown to have activity on DNA substrates within nucleosomes. DNA polymerase β (Pol β), however, exhibits drastically reduced or no activity on nucleosomal DNA...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28065385/processing-of-the-abasic-sites-clustered-with-the-benzo-a-pyrene-adducts-by-the-base-excision-repair-enzymes
#8
Lidia V Starostenko, Nadejda I Rechkunova, Natalia A Lebedeva, Alexander A Lomzov, Vladimir V Koval, Olga I Lavrik
The major enzyme in eukaryotic cells that catalyzes the cleavage of apurinic/apyrimidinic (AP or abasic) sites is AP endonuclease 1 (APE1) that cleaves the phosphodiester bond on the 5'-side of AP sites. We found that the efficiency of AP site cleavage by APE1 was affected by the benzo[a]pyrenyl-DNA adduct (BPDE-dG) in the opposite strand. AP sites directly opposite of the modified dG or shifted toward the 5' direction were hydrolyzed by APE1 with an efficiency moderately lower than the AP site in the control DNA duplex, whereas AP sites shifted toward the 3' direction were hydrolyzed significantly less efficiently...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#9
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
February 2017: Pathology
https://www.readbyqxmd.com/read/27994014/human-ap-endonuclease-ape1-is-acetylated-at-dna-damage-sites-in-chromatin-and-acetylation-modulates-its-dna-repair-activity
#10
Shrabasti Roychoudhury, Somsubhra Nath, Heyu Song, Muralidhar L Hegde, Larry J Bellot, Anil K Mantha, Shiladitya Sengupta, Sutapa Ray, Amarnath Natarajan, Kishor K Bhakat
Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome, inhibit transcription and block replication. The primary enzyme to repair AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the Base Excision Repair (BER) pathway. Although the mechanism by which APE1 repairs AP sites in vitro has been extensively investigated, it is largely unknown how APE1 repairs AP sites in cells. Here, we show that APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle...
December 19, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27986089/the-anti-inflammatory-role-of-extranuclear-apurinic-apyrimidinic-endonuclease-1-redox-effector-factor-1-in-reactive-astrocytes
#11
Hyunjung Baek, Chae Seong Lim, Hee Sun Byun, Hyun Sil Cho, Yu Ran Lee, Yong Sup Shin, Hyun-Woo Kim, Byeong Hwa Jeon, Dong Woon Kim, Jinpyo Hong, Gang Min Hur, Jin Bong Park
Apurinic/apyrimidinic endonuclease 1 (APE1), a ubiquitous multipurpose protein, is also known as redox effector factor-1 (Ref-1). It is involved in DNA repair and redox signaling and, in turn, oxidative stress-induced neurodegeneration. Although previous studies have demonstrated that APE1/Ref-1 functions as a negative regulator of inflammatory response via several mechanisms in neuronal cells, little is known about the roles of APE1/Ref-1 in glial cells. In this study, we found that cytoplasmic APE1/Ref-1 expression was upregulated in reactive astrocytes of the kainic acid- or lipopolysaccharide (LPS)-injected hippocampus...
December 16, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27923991/a-specific-dna-nanoprobe-for-tracking-the-activities-of-human-apurinic-apyrimidinic-endonuclease-1-in-living-cells
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
December 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
#20
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 mediated by growth arrest and DNA damage inducible, alpha (GADD45A)...
October 8, 2016: Journal of Investigative Dermatology
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