• Title/Summary/Keyword: Atf3

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Activating Transcription Factor 3 is a Molecular Target for Apoptotic Effect of Silymarin in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.29 no.3
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    • pp.281-288
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    • 2016
  • Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.

Activating Transcription Factor 1 is a Prognostic Marker of Colorectal Cancer

  • Huang, Guo-Liang;Guo, Hong-Qiang;Yang, Feng;Liu, Ou-Fei;Li, Bin-Bin;Liu, Xing-Yan;Lu, Yan;He, Zhi-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.1053-1057
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    • 2012
  • Objective: Identifying cancer-related genes or proteins is critical in preventing and controlling colorectal cancer (CRC). This study was to investigate the clinicopathological and prognostic value of activating transcription factor 1 (ATF1) in CRC. Methods: Protein expression of ATF1 was detected using immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1 in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox regression models. Results: The ATF1 protein expression was significantly lower in tumor tissues than corresponding normal tissues (51.5% and 71.1%, respectively, P = 0.038). No correlation was found between ATF1 expression and the investigated clinicopathological parameters, including gender, age, depth of invasion, lymph node status, metastasis, pathological stage, vascular tumoral emboli, peritumoral deposits, chemotherapy and original tumor site (all with P > 0.05). Patients with higher ATF1 expression levels have a significantly higher survival rate than that with lower expression (P = 0.026 for overall survival, P = 0.008 for progress free survival). Multivariate Cox regression model revealed that ATF1 expression and depth of invasion were the predictors of the overall survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P = 0.005) in CRC. Conclusions: Higher ATF1 expression is a predictor of a favorable outcome for the overall survival and progress free survival in CRC.

Effect of Steroid Hormones on the Expression of c-Fos, CREB, ATF, and HSP70 in Rat Uterus (흰쥐 자궁에서 스테로이드호르몬에 의한 c-Fos, CREB, ATF 및 HSP70의 발현에 관한 연구)

  • Lee, Young-Ki;Kim, Sung-Rye
    • Clinical and Experimental Reproductive Medicine
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    • v.25 no.3
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    • pp.305-313
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    • 1998
  • Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle. However there is little information about the effect of estrogen (E) and progesterone (P) on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E and/or P-induced expression of c-Fos, CREB, ATF and HSP70 in rat uterus. Rats, ovariectomized (OVX) for two weeks, were divided into 6 experimental groups, 1) OVX, 2) OVX+V, 3) OVX+E, 4) OVX+P, 5) OVX+E+V, 6) OVX+E+P, and western blotting assay for nuclear extract and immunohistochemical staining were carried out for each experimental group. Treatment of E $(10{\mu}g)$ showed to increase the expression of c-Fos, CREB, ATF, and HSP70, and maximal expression was occured at $3\sim6$ hr after E administration. P (1mg) also increased, but much less than E, the expression of c-Fos, ATF, and HSP70. However, P did not reveal any effect on the expression CREE. P treatment 4 hr after E injection decreased c-Fos, CREB, and ATF expression, but did not show any change in the E-induced HSP70 expression. In immunohistochemical study c-Fos-, CREB-, and ATF-immunoreactivities were confined to the cells of luminal epithelium of uterine endometrium. These results suggest that proliferation and differentiation of rat uterus during reproductive cycle may mediated via expression of transcription factors, such as c-Fos, CREB, ATF, and HSP70.

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Dependency on p53 in Expression Changes of ATF3 and NAG-1 Induced by EGCG, Genistein, and Resveratrol (EGCG, genistein, resveratrol 처리에 의한 ATF3와 NAG-1 유전자 발현변화의 p53 의존성 분석)

  • Kim, Min-Jeong;Kim, Hyun-Ji;Seo, Yu-Mi;Lee, Eun-Joo;Kim, Jong-Sik
    • Journal of Life Science
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    • v.28 no.5
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    • pp.615-620
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    • 2018
  • Epigallocatechin-3-gallate (EGCG), one of catechins of green tea, has been known to possess anti-oxidation, anti-inflammation, and anti-cancer effects. The present study analyzed global gene expression changes in EGCG-treated HCT116 cells and p53-null HCT116 cells by oligo DNA microarray analysis. Among the differentially expressed genes in EGCG-treated HCT116 cells, four were selected that are known as tumor suppressor genes (activating transcription factor 3 [ATF3], cyclin dependent kinase inhibitor 1A [CDKN1A], DNA damage-inducible transcript 3 [DDIT3] and non-steroidal anti-inflammatory drug activated gene [NAG-1]) and their expression was compared to the expression of genes in p53-null HCT116 cells. We found that the expression of these genes was not dependent on their p53 status except for NAG-1, which was only up-regulated in HCT116. The results of RT-PCR and Western blot analysis showed that ATF3 up-regulation by EGCG was not affected by the presence of p53, whereas NAG-1 expression was not induced in p53-null HCT116 cells. We also detected ATF3 and NAG-1 expression changes through genistein and resveratrol treatment. Interestingly, genistein could not up-regulate ATF3 regardless of p53 status, but genistein could induce NAG-1 only in HCT116 cells. Resveratrol could significantly induce NAG-1 as well as ATF3 independent of p53 presence. These results indicate that EGCG, genistein and resveratrol may have different anti-cancer effects. Overall, the results of this study may help to increase our understandings of molecular mechanisms on anti-cancer activities mediated by EGCG, genistein and resveratrol in human colorectal cancer cells.

Study on Vinyl Coating Cultivation of Potatoes under Low Temperature Conditions (조기 재배시 감자의 비닐 피복 재배 연구)

  • Choi, Kwan Soo;Jung, Gun Ho
    • Korean Journal of Plant Resources
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    • v.30 no.5
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    • pp.556-564
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    • 2017
  • Appropriate soil temperature and early planting of potato is very important for the successful potato-soybean cropping system in central region of South Korea. This experiment was carried out to determine the effect of mulching materials on the growth and yield of potato (Solanum tuberosum L.). Five different mulch treatments were had been applied on an upland soil as follows ; no mulch (NM), transparent film (TF), transparent film + additional transparent film (TF + ATF), black film (BF), and black film + additional transparent film (ATF). In the period of sowing time to removing additional films, mean soil temperature of the treatments was in the order of TF+ATF > TF > BR+ATF > BF as $20.3^{\circ}C$ > $18.5^{\circ}C$ > $16.1^{\circ}C$ > $15.4^{\circ}C$, respectively and that of NM was $13.8^{\circ}C$. The accumulated soil temperature was TF > NM > BF during the removing additional films to earthing at inter-tillage. On the changes in the soil temperature during a whole day, the temperature in the BF was lower than NM during around 18:00 PM to 12:00 NM, while NM was higher than BF in the time period of 10:00AM to 21:00PM. The sequence of potato sprout emergence was 15 > 18 > 20 > 22 days of TF+ATF, TF, BF+ATF, and BF, respectively and that of NM was 24 days. Comparing to the NM, potato sprout emergence was observed on the TF+ATF treated plot as early as 9 days. At 10 days before harvest, the significant difference in the tuber dry weight had been observed and the sequence tuber weight was in the order of TF > TF+ATF > BF+ATF > BF > NM. The potato yields of TF, TF+ATF, and BF+ATF were increased of 40.7, 37.3, and 22% as compared to NM ($2,805kg\;10a^{-1}$), but almost same yield in the BF. The differences of tuber dry weight and potato yields was co-related with the temperature rise of soil by the application of mulching materials on soil. Based on these results, application of mulching film had been very effective to increase the tuber size and the yield of potato by the temperature rise during seedling stage of potato. Transparent mulching was better than black mulching especially for the emergence of sprout of potato in relation to minimizing cooling injury.

Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice

  • Kim, Suji;Song, No-Joon;Chang, Seo-Hyuk;Bahn, Gahee;Choi, Yuri;Rhee, Dong- Kwon;Yun, Ui Jeong;Choi, Jinhee;Lee, Jeon;Yoo, Jae Hyuk;Shin, Donghan;Park, Ki-Moon;Kang, Hee;Lee, Sukchan;Ku, Jin-Mo;Cho, Yoon Shin;Park, Kye Won
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.107-116
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    • 2019
  • The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

miRNA-103a-3p Promotes Human Gastric Cancer Cell Proliferation by Targeting and Suppressing ATF7 in vitro

  • Hu, Xiaoyi;Miao, Jiyu;Zhang, Min;Wang, Xiaofei;Wang, Zhenzhen;Han, Jia;Tong, Dongdong;Huang, Chen
    • Molecules and Cells
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    • v.41 no.5
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    • pp.390-400
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    • 2018
  • Studies have revealed that miR-103a-3p contributes to tumor growth in several human cancers, and high miR-103a-3p expression is associated with poor prognosis in advanced gastric cancer (GC) patients. Moreover, bioinformatics analysis has shown that miR-103a-3p is upregulated in The Cancer Genome Atlas (TCGA) stomach cancer cohort. These results suggest that miR-103a-3p may function as an oncogene in GC. The present study aimed to investigate the role of miR-103a-3p in human GC. miR-103a-3p expression levels were increased in 33 clinical GC specimens compared with adjacent nontumor stomach tissues. Gain- and loss-of-function studies were performed to identify the correlation between miR-103a-3p and tumorigenesis in human GC. Inhibiting miR-103a-3p suppressed GC cell proliferation and blocked the S-G2/M transition in MKN-45/SGC-7901 cells, whereas miR-103a-3p overexpression improved GC cell proliferation and promoted the S-G2/M transition in vitro. Bioinformatics and dual-luciferase reporter assays confirmed that ATF7 is a direct target of miR-103a-3p. Analysis of the TCGA stomach cancer cohort further revealed that miR-103a-3p expression was inversely correlated with ATF7 expression. Notably, silencing ATF7 showed similar cellular and molecular effects as miR-103a-3p overexpression, namely, increased GC cell proliferation, improved CDK2 expression and decreased P27 expression. ATF7 overexpression eliminated the effects of miR-103a-3p expression. These findings indicate that miR-103a-3p promotes the proliferation of GC cell by targeting and suppressing ATF7 in vitro.

Anti-thrombotic Effects of Modified Jeho-tang using a $FeCl_3$-induced Carotid Arterial Thrombosis Model

  • Bang, Jihye;Lee, Ki Mo;Kim, Bu-Yeo;Lee, Jeong-Hwa;Lee, In Sun;Jeon, Won Kyung
    • The Journal of Korean Medicine
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    • v.34 no.2
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    • pp.51-58
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    • 2013
  • Objectives: The aim of this study was to examine the antithrombotic effects of the four herbal ingredients (Mume Fructus, MF; Santali Albi Lignum, SAL; Amomi Tsao-Ko Fructus, ATF; and Amomi Fructus, AF) of modified Jeho-tang (MJHT) in a ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis model. Methods: Thirty minutes prior to a 35% $FeCl_3$ application, Sprague-Dawley (SD) rats were injected with saline, MF, SAL, ATF or AF (100 mg/kg, intraperitoneal injection), respectively. The effect of the MJHT ingredients was examined for time to occlusion (TTO) and thrombus weight (TW) in a $FeCl_3$-induced thrombosis model. Histological analysis was performed to examine the effect of the MJHT ingredients on collagen fiber damage using hematoxylin & eosin and Masson's trichrome staining. Results: Compared with vehicle treatment, MF, SAL and ATF treatment delayed TTO (vehicle, $8.11{\pm}0.60$ min; MF, $16.67{\pm}1.03$ min; SAL, $17.50{\pm}1.52$ min and ATF, $13.33{\pm}1.21$ min; P < 0.001) and inhibited thrombus formation (vehicle, $0.79{\pm}0.03$ mg/mm; MF, $0.61{\pm}0.07$ mg/mm; SAL, $0.57{\pm}0.03$ mg/mm and ATF, $0.72{\pm}0.02$ mg/mm; P < 0.001). In addition, each herbal ingredient of MJHT except for AF prevented the collagen fiber damage induced by a 35% $FeCl_3$ application. These results indicate that the MJHT ingredients MF ${\geq}$ SAL ${\geq}$ ATF ${\geq}$ AF possess antithrombotic activity in a $FeCl_3$-induced carotid arterial thrombosis. Conclusions: Altogether, these results are the first evidence that the MJHT ingredients MF, SAL and ATF have the ability to prevent vascular damage and thrombus formation in $FeCl_3$-induced carotid arterial thrombosis.

The Monitoring Study of Exchange Cycle of Automatic Transmission Fluid (자동변속기유(ATF) 교환주기 모니터링 연구)

  • Lim, Young-Kwan;Jung, Choong-Sub;Lee, Jeong-Min;Han, Kwan-Wook;Na, Byung-Ki
    • Applied Chemistry for Engineering
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    • v.24 no.3
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    • pp.274-278
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    • 2013
  • Automatic transmission fluid (ATF) is used as an automatic transmission in the vehicle or as a characterized fluid for automatic transmission. Recently, vehicle manufacturers usually guarantee for changing fluids over 80000~100000 km mileage or no exchange. However, most drivers usually change ATF below every 50000 km driving distance when driving in Republic of Korea according to a survey from the Korea Institute of Petroleum Management which can cause both a serious environmental contamination by the used ATF and an increase in the cost of driving. In this study, various physical properties such as flash point, pour point, kinematic viscosity, dynamic viscosity at low temperature, total acid number and four-ball test were investigated for both fresh ATF and used ATF after the actual vehicle driving distance of 50000 km and 100000 km. It was shown that most physical properties were suitable for the specification of ATF, but the foam characteristics of the used oil after running 100000 km was unsuitable for the specification of fresh ATF. Therefore, the exchange cycle of ATF every 80000~100000 km driving distance is recommended considering great positive contributions to preventing environmental pollution and reducing driving cost.

Core analysis of accident tolerant fuel cladding for SMART reactor under normal operation and rod ejection accident using DRAGON and PARCS

  • Pourrostam, A.;Talebi, S.;Safarzadeh, O.
    • Nuclear Engineering and Technology
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    • v.53 no.3
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    • pp.741-751
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    • 2021
  • There has been a deep interest in trying to find better-performing fuel clad motivated by the desire to decrease the likelihood of the reactor barrier failure like what happened in Fukushima in recent years. In this study, the effect of move towards accident tolerant fuel (ATF) cladding as the most attracting concept for improving reactor safety is investigated for SMART modular reactor. These reactors have less production cost, short construction time, better safety and higher power density. The SiC and FeCrAl materials are considered as the most potential candidate for ATF cladding, and the results are compared with Zircaloy cladding material from reactor physics point of view. In this paper, the calculations are performed by generating PMAX library by DRAGON lattice physics code to be used for further reactor core analysis by PARCS code. The differential and integral worth of control and safety rods, reactivity coefficient, power and temperature distributions, and boric acid concentration during the cycle are analyzed and compared from the conventional fuel cladding. The rod ejection accident (REA) is also performed to study how the power changed in response to presence of the ATF cladding in the reactor core. The key quantitative finding can be summarized as: 20 ℃ (3%) decrease in average fuel temperature, 33 pcm (3%) increase in integral rod worth and cycle length, 1.26 pcm/℃ (50%) and 1.05 pcm/℃ (16%) increase in reactivity coefficient of fuel and moderator, respectively.