• Title/Summary/Keyword: APE1

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Ape1/Ref-1 Stimulates GDNF/GFR ${\alpha}$ 1-mediated Downstream Signaling and Neuroblastoma Proliferation

  • Kang, Mi-Young;Kim, Kweon-Young;Yoon, Young;Kang, Yoon-Sung;Kim, Hong-Beum;Youn, Cha-Kyung;Kim, Dong-Hui;Kim, Mi-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.349-356
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    • 2009
  • We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor ${\alpha}$ 1 (GFR ${\alpha}$ 1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFR ${\alpha}$ 1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR ${\alpha}$ 1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFR ${\alpha}$ 1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR ${\alpha}$ 1-specific RNA experiments demonstrated that the downregulation of GFR ${\alpha}$ 1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC ${\gamma}$-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR ${\alpha}$ signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

Chemopreventive Effect of Quercetin, Vitamin C and Trolox Against the Organic Extract of Airborne Particulate Matter Induced Genotoxicity in A549 Human Lung Carcinoma Cells (대기부유분진추출물로 야기된 DNA 손상에 대한 Quercetin, Vitamin C 및 Trolox 의 보호효과)

  • Kim, Nam-Yee;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.51 no.4
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    • pp.239-245
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    • 2007
  • In order to evaluate the genotoxicity of airborne particulate matter extracted with dichloromethane (APE), the rat microsome mediated (S-9) or DNA repair enzyme treated Comet assays were performed using the single cell gel electrophoresis in A549 human lung carcinoma cells. It was found that the cells interacting with APE showed more DNA single-strand breaks relative to untreated cells. The genotoxicity of APE was increased with the treatment of S-9 mixture. Microsome mediated DNA damage was inhibited by CYP1Al inhibitor, quercetin. The APE also showed oxidative DNA damage evaluated by endonuclease III treatment. Oxidative DNA damage of APE was inhibited by antioxidants such as vita- min C and Trolox. We also found that the vegetables or fruits extract may reduce APE-induced genotoxicity by their anti- oxidant activity and CYP1A1 inhibition.

Identification of New Potential APE1 Inhibitors by Pharmacophore Modeling and Molecular Docking

  • Lee, In Won;Yoon, Jonghwan;Lee, Gunhee;Lee, Minho
    • Genomics & Informatics
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    • v.15 no.4
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    • pp.147-155
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    • 2017
  • Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

Evaluation of the antinociceptive activities of natural propolis extract derived from stingless bee Trigona thoracica in mice

  • Nurul Alina Muhamad Suhaini;Mohd Faeiz Pauzi;Siti Norazlina Juhari;Noor Azlina Abu Bakar;Jee Youn Moon
    • The Korean Journal of Pain
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    • v.37 no.2
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    • pp.141-150
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    • 2024
  • Background: Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R2 = 0.999) and caffeic acid (R2 = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

  • Li, Qing;Wang, Jian-Min;Peng, Yu;Zhang, Shi-Heng;Ren, Tao;Luo, Hao;Cheng, Yi;Wang, Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5145-5151
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    • 2013
  • Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

Alteration of Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1 in Human Mon-small Cell Lung Cancer (비소세포 폐암조직에시 Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1의 발현변화)

  • Yoo, Dae-Goon;Song, Yun-Jeong;Cho, Eun-Jung;Kang, Min-Woong;Han, Jong-Hee;Na, Myung-Hoon;Lim, Seung-Pyung;Yu, Jae-Hyeon;Jeon, Byeong-Hwa;Lee, Young
    • Journal of Chest Surgery
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    • v.40 no.8
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    • pp.529-535
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    • 2007
  • Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.

Automatic Post Editing Research (기계번역 사후교정(Automatic Post Editing) 연구)

  • Park, Chan-Jun;Lim, Heui-Seok
    • Journal of the Korea Convergence Society
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    • v.11 no.5
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    • pp.1-8
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    • 2020
  • Machine translation refers to a system where a computer translates a source sentence into a target sentence. There are various subfields of machine translation. APE (Automatic Post Editing) is a subfield of machine translation that produces better translations by editing the output of machine translation systems. In other words, it means the process of correcting errors included in the translations generated by the machine translation system to make proofreading. Rather than changing the machine translation model, this is a research field to improve the translation quality by correcting the result sentence of the machine translation system. Since 2015, APE has been selected for the WMT Shaed Task. and the performance evaluation uses TER (Translation Error Rate). Due to this, various studies on the APE model have been published recently, and this paper deals with the latest research trends in the field of APE.

Cytoprotective effect of rhamnetin on miconazole-induced H9c2 cell damage

  • Lee, Kang Pa;Kim, Jai-Eun;Park, Won-Hwan
    • Nutrition Research and Practice
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    • v.9 no.6
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    • pp.586-591
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    • 2015
  • BACKGROUND/OBJECTIVES: Reactive oxygen species (ROS) formation is closely related to miconazole-induced heart dysfunction. Although rhamnetin has antioxidant effects, it remained unknown whether it can protect against miconazole-induced cardiomyocyte apoptosis. Thus, we investigated the effects of rhamnetin on miconazole-stimulated H9c2 cell apoptosis. MATERIALS/METHODS: Cell morphology was observed by inverted microscope and cell viability was determined using a WelCount$^{TM}$ cell proliferation assay kit. Miconazole-induced ROS production was evaluated by fluorescence-activated cell sorting with 6-carboxy-2',7'-dichlorofluoroscein diacetate ($H_2DCF$-DA) stain. Immunoblot analysis was used to determine apurinic/apyrimidinic endonuclease 1 (APE/Ref-1) and cleaved cysteine-aspartic protease (caspase) 3 expression. NADPH oxidase levels were measured using real-time polymerase chain reaction. RESULTS: Miconazole (3 and $10{\mu}M$) induced abnormal morphological changes and cell death in H9c2 cells. Rhamnetin enhanced the viability of miconazole ($3{\mu}M$)-treated cells in a dose-dependent manner. Rhamnetin (1 and $3{\mu}M$) treatment downregulated cleaved caspase 3 and upregulated APE/Ref-1 expression in miconazole-stimulated cells. Additionally, rhamnetin significantly reduced ROS generation. CONCLUSIONS: Our data suggest that rhamnetin may have cytoprotective effects in miconazole-stimulated H9c2 cardiomyocytes via ROS inhibition. This effect most likely occurs through the upregulation of APE/Ref-1 and attenuation of hydrogen peroxide levels.

Statistical Characteristics of East Sea Mesoscale Eddies Detected, Tracked, and Grouped Using Satellite Altimeter Data from 1993 to 2017 (인공위성 고도계 자료(1993-2017년)를 이용하여 탐지‧추적‧분류한 동해 중규모 소용돌이의 통계적 특성)

  • LEE, KYUNGJAE;NAM, SUNGHYUN;KIM, YOUNG-GYU
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.24 no.2
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    • pp.267-281
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    • 2019
  • Energetic mesoscale eddies in the East Sea (ES) associated with strong mesoscale variability impacting circulation and environments were statistically characterized by analyzing satellite altimeter data collected during 1993-2017 and in-situ data obtained from four cruises conducted between 2015 and 2017. A total of 1,008 mesoscale eddies were detected, tracked, and identified and then classified into 27 groups characterized by mean lifetime (L, day), amplitude (H, m), radius (R, km), intensity per unit area (EI, $cm^2/s^2/km^2$), ellipticity (e), eddy kinetic energy (EKE, TJ), available potential energy (APE, TJ), and direction of movement. The center, boundary, and amplitude of mesoscale eddies identified from satellite altimeter data were compared to those from the in-situ observational data for the four cases, yielding uncertainties in the center position of 2-10 km, boundary position of 10-20 km, and amplitude of 0.6-5.9 cm. The mean L, H, R, EI, e, EKE, and APE of the ES mesoscale eddies during the total period are $95{\pm}104$ days, $3.5{\pm}1.5cm$, $39{\pm}6km$, $0.023{\pm}0.017cm^2/s^2/km^2$, $0.72{\pm}0.07$, $23{\pm}21TJ$, and $588{\pm}250TJ$, respectively. The ES mesoscale eddies tend to move following the mean surface current rather than propagating westward. The southern groups (south of the subpolar front) have a longer L, larger H, R, and higher EKE, APE; and stronger EI than those of the northern groups and tend to move a longer distance following surface currents. There are exceptions to the average characteristics, such as the quasi-stationary groups (the Wonsan Warm, Wonsan Cold, Western Japan Basin Warm, and Northern Subpolar Frontal Cold Eddy groups) and short-lived groups with a relatively larger H, higher EKE, and APE and stronger EI (the Yamato Coastal Warm, Central Yamato Warm, and Eastern Japan Basin Coastal Warm eddy groups). Small eddies in the northern ES hardly resolved using the satellite altimetry data only, were not identified here and discussed with potential over-estimations of the mean L, H, R, EI, EKE, and APE. This study suggests that the ES mesoscale eddies 1) include newly identified groups such as the Hokkaido and the Yamato Rise Warm Eddies in addition to relatively well-known groups (e.g., the Ulleung Warm and the Dok Cold Eddies); 2) have a shorter L; smaller H, R, and lower EKE; and stronger EI and higher APE than those of the global ocean, and move following surface currents rather than propagating westward; and 3) show large spatial inhomogeneity among groups.

Sources of Alkylphenol Polyethoxylate and their Fate in the Central Nakdong River Basin (낙동강 중류 수계에 있어서 Alkylphenol Polyethoxylate의 오염원과 잔류특성)

  • Lee, Se-Han;Lee, Shun-Hwa;Lee, Chul-Hee
    • Journal of Korean Society of Environmental Engineers
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    • v.27 no.12
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    • pp.1277-1284
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    • 2005
  • Alkylphenol Polyethoxylate(APEs) and their metabolites were determined in the aquatic environment in the central Nakdong river basin. The concentrations of APE's ranged between $0.62{\sim}11.70\;{\mu}g/L$ from the Nakdong and the Kumho rivers, and were $70.00{\sim}212.50\;{\mu}g/L$ in the samples from the 3rd industrial complex stream and the Dalseo stream, which are both heavily polluted by industrial wastewater and domestic wastewater. The APEs revealed a removal rate of more than 87% by biodegradation and adsorption etc. in the wastewater treatment plant. Nonylphenol polyethoxylates(NPnEO) and Nonylphenol carboxylic acid(NPnEC) consisted of APE metabolites shifted from NP($n=4{\sim}10$)EO and NP($n=4{\sim}10$)EC to NP($n=1{\sim}3$)EO and NP($n=1{\sim}3$)EC or removed by the adsorption of activated sludge during the biological wastewater treatment process. Upper streams have a higher distributed rate of NP($n=7{\sim}10$)EO than water downstream. Continuous monitoring is necessary for non-point sources as well as point sources, such as a wastewater treatment plant. Effluent concentrations of nonylphenol(NP) in industrial wastewater and domestic wastewater averaged about 4.33 and $1.70\;{\mu}g/L$, respectively. In addition, the removal rate average was 90% in the wastewater treatment plant. NP concentrations in the rivers did not exceed $1.0\;{\mu}g/L$, which are prescribed by environmental risk concentration in the USA and Europe. However, NP required continuous monitoring, which detected over $0.1\;{\mu}g/L$ in all river areas.