• Title/Summary/Keyword: SRC-1

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Enhancement of skin barrier and hydration-related molecules by protopanaxatriol in human keratinocytes

  • Lee, Jeong-Oog;Hwang, So-Hyeon;Shen, Ting;Kim, Ji Hye;You, Long;Hu, Weicheng;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.354-360
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    • 2021
  • Background: Protopanaxatriol (PPT) is a secondary intestinal metabolite of ginsenoside in ginseng. Although the effects of PPT have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of PPT are poorly understood. Methods: HaCaT cells were treated with PPT in a dose-dependent manner. mRNA and protein levels which related to skin barrier and hydration were detected compared with retinol. Luciferase assay was performed to explore the relative signaling pathway. Western blot was conducted to confirm these pathways and excavated further signals. Results: PPT enhanced the expression of filaggrin (FLG), transglutaminase (TGM)-1, claudin, occludin and hyaluronic acid synthase (HAS) -1, -2 and -3. The mRNA expression levels of FLG, TGM-1, HAS-1 and HAS-2 were suppressed under NF-κB inhibition. PPT significantly augmented NF-κB-luc activity and upregulated Src/AKT/NF-κB signaling. In addition, PPT also increased phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 and upstream MAPK activators (MEK and MKK). Furthermore, transcriptional activity of AP-1 and CREB, which are downstream signaling targets of MAPK, was enhanced by PPT. Conclusion: PPT improves skin barrier function and hydration through Src/AKT/NF-κB and MAPK signaling. Therefore, PPT may be a valuable component for cosmetics or treating skin disorders.

Src Family Kinase Inhibitor PP2 Induces LC3 Conversion in a Manner That is Uncoupled from Autophagy and Increases Apoptosis in Multidrug-Resistant Cells

  • Kim, Yun-Ki;Ahn, Jun-Ho;Lee, Mi-Chael
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.393-398
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    • 2012
  • Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

한우 수정란 생산에 있어서 체외성숙의 생물학적 요인 III. 소 난포란의 체외성숙에 있어서 단백질 변화

  • 박용수;이재협;변명대;박흠대
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.117-117
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    • 2003
  • 체외에서 한우 난포란의 감수분열과 배발달 능력의 획득에는 단백질 합성이 수반되어야 한다. 그러나 이러한 변화와 관련된 연구 보고는 거의 전무한 실정이다. 본 실험은 난자의 핵성숙과 관련된 세포질내 단백질 변화를 파악하기 위하여, 체외성숙 시간에 다른 배발달율과 세포질내 단백질을 비교하여 배발달능력 획득과 관련 있는 단백질을 규명하고자 실시하였다. 한우 난소에서 2-8mm의 가시난포로부터 난포란을 회수하였다. 회수된 난포란은 10% FBS와 호르몬이 첨가된 TCM199 용액에서 18시간 또는 24시간 체외성숙을 실시하였다. 난자 세포질내 단백질 변화는 2D gel electrophoresis를 이용하였고, 유의적인 변화를 나타낸 spot은 peptide mass fingerprinting을 통하여 단백질 동정을 실시하였다. 체외수정은 fer-TALP 용액을, 체외배양은 CR1aa 용액을 배양 3일째까지는 0.3% BSA, 그 이후에는 10% FBS와 난관상피세포를 첨가하여 사용하였다. 통계분석은 t-test를 이용하였다. 난자의 세포질에 대한 이차원전기영동 결과 29개의 단백질 spot들을 확인하였다. 한편 체외성숙 18시간째에 PB가 출현된 난자는 PB가 출현되지 않은 난자에 비하여 15개의 spot에서 유의적인 변화를 나타냈다. 이들 중 4개의 단백질 spot은 낮았고, 11개 spot의 수준은 높은 경향이었다. 체외성숙 18시간째와 24시간째의 배발달율을 조사한 결과 18시간째에서 유의적으로 높은 배반포 발달율을 나타냈다. 그리고 체외성숙 18시간과 24시간째 난자의 세포질내 단백질 spot들의 변화를 비교한 결과 PB가 출현된 난자 세포질에서 단백질의 변화와 유사한 경향이었다. 그러나 2개의 단백질 spot은 상반된 경향을 나타냈다. 따라서 본 실험에서 난자의 핵성숙과 관련 있는 15개의 spot을 확인하였고, 이들 단백질 spot중에서 2개가 배발달 능력과 관련이 있을 것으로 사료된다.보다는 육질등급에 많은 영향을 받는 것으로 판단된다. 한편 육질 1등급에서 배발달율이 낮은 이유는 육질 향상을 목적으로 암소를 비육 하는 경우 발생하는 번식장애와 밀접한 관계가 있는 것으로 사료된다.각각 가장 높았다. 배양 8일째 배반포의 세포수에 있어서 총세포수와 TE 세포수는 차이가 없었으나, ICM 세포수가 l0mg 첨가군에서 가장 높았다. 본 실험 결과에서 체외성숙 배지에 NEAA와 EAA 첨가가 배발달율에는 효과가 없었지만, 첨가농도의 증가에 따라 ICM 세포수가 증가하였다. 한편 체외성숙 배지에 LAH 첨가는 첨가 농도가 높을수록 배발달율은 낮았지만 ICM 세포수는 증가하였다.에 Csk가 관여하고 있음을 알 수 있다. 결론적으로 성적 성숙에 따른 생쥐 정소 내 Src-Csk loop의 발현과 Src kinase 활성의 변동은 정소 내 간충조직, 세정관 상피의 증식 및 기능적 분화 과정을 매개하는 생리적 활성분자 수용체 하위의 신호전달 과정에 Src-Csk loop에 의한 조절가능성을 확인할 수 있었다.rugrene의 향기성분이 주요 성분군으로 확인되었다. 2. 생강나무에서 생강의 향기를 발산하는 성분으로는 $\beta$-myrcene, o-terpinolene, phellandrone, ι-limonene, $\beta$-eudesmol, $\delta$-cadinone, elemol, trans-caryophyllene으로 동정되었으며 그 중에서도 phellandrene, $\beta$-eudesmol이 주된 역할을 하는 성분으로 확인하였다. 유의적인 관련성이 나타났고, 복부 비만의 지표인 허리엉덩이둘레비는 GPT, alkaline phosphatase, 공복시 혈당 및 MCV 등 다양한 건강지표와 관련성을 나타내어 향후 비만에 있어 다양한 혈액 성상의 변화 및 역할규명에 대한 연구가 이루어져야 할 것으로 본다.hat

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An Analytical Study on Encased Steel Composite Columns Fire Resistance According to Axial Force Ratio (화재시 축력비에 따른 매입형 합성기둥의 내화성능에 대한 해석적 연구)

  • Kim, Ye-Som;Choi, Byong-Jeong
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.24 no.1
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    • pp.97-107
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    • 2020
  • In this study, finite element analysis was carried out through the finite element analysis program (ANSYS) to investigate the fire resistance of composite columns in fire. Transient heat transfer analysis and static structural analysis were performed according to ASTM E 119 heating curve and axial force ratio 0.7, 0.6, 0.5 by applying stress-strain curves according to temperature, and loading heating experiments were carried out under the same conditions. In addition, the nominal compressive strength of the composite column according to the heating time according to the standard(Eurocode 4) was calculated and expressed as the axial force ratio and compared with the analytical and experimental values. Through the analysis, As a result of finite element analysis, the fire resistance time was 180 minutes and similar value to the experimental value was obtained, whereas the fire resistance time 150 minutes and 60 minutes were derived from the axial force ratios 0.6 and 0.7. In addition, it was confirmed that the fire resistance time according to the axial force ratio calculated according to the reference equation (Eurocode 4) was lower than the actual experimental value. However, it was confirmed that the standard(Eurocode 4) was higher than the experimental value at the axial force ratio of 0.7. Accordingly, it is possible to confirm the fire resistance characteristics(time-axial force ratio relationship) of the SRC column at high axial force, and to use the experimental and anaylsis data of the SRC column as the data for verification based on Eurocode.

Analysis of Nuclear Power Plant Load Follow Operation by Temperature Reduction Method (냉각재 온도 감소 장식에 의한 원자력발전소 부하 추종 운전 해석)

  • Park, Sang-Yoon;Park, Goon-Cherl;Lee, Un-Cherl;Kang, Chang-Sun;Kim, Chang-Hyo;Chung, Chang-Hyun
    • Nuclear Engineering and Technology
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    • v.18 no.3
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    • pp.209-217
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    • 1986
  • The inlet coolant temperature reduction technique has been used to extend the load follow operation further in the end-of-cycle-life(EOL). In order to simulate the technique and calculate the nuclear characteristics of a PWR core according to the load follow operation, the three dimensional computing system has been established. The analysis was performed in both MINB and SPINR modes of typical 12-3-6-3 locad follow operation for the EOL of KNU-1 plant. Moreover, the capability of return-to-power has been also tested for those two modes with the system analysis by the RETRAN-02 code. The results show that it has no difficulty to extend the load follow operation further in the EOL by applying the inlet coolant temprature reduction, and also the spinning reserve capacity(SRC) increases by 13% in MINB mode and 14% in SPINR mode Bore that used by control rods only, for 14$^{\circ}$ F drop in the inlet temperature.

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Luteolin attenuates migration and invasion of lung cancer cells via suppressing focal adhesion kinase and non-receptor tyrosine kinase signaling pathway

  • Masraksa, Wuttipong;Tanasawet, Supita;Hutamekalin, Pilaiwanwadee;Wongtawatchai, Tulaporn;Sukketsiri, Wanida
    • Nutrition Research and Practice
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    • v.14 no.2
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    • pp.127-133
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    • 2020
  • BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells

  • Cho, Eunah;Kwon, Yeo-Jung;Ye, Dong-Jin;Baek, Hyoung-Seok;Kwon, Tae-Uk;Choi, Hyung-Kyoon;Chun, Young-Jin
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.591-602
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    • 2019
  • Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

Extracting the Distribution Potential Area of Debris Landform Using a Fuzzy Set Model (퍼지집합 모델을 이용한 암설지형 분포 가능지 추출 연구)

  • Wi, Nun-Sol;JANG, Dong-Ho
    • Journal of The Geomorphological Association of Korea
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    • v.24 no.1
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    • pp.77-91
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    • 2017
  • Many debris landforms in the mountains of Korea have formed in the periglacial environment during the last glacial stage when the generation of sediments was active. Because these landforms are generally located on steep slopes and mostly covered by vegetation, however, it is difficult to observe and access them through field investigation. A scientific method is required to reduce the survey range before performing field investigation and to save time and cost. For this purpose, the use of remote sensing and GIS technologies is essential. This study has extracted the potential area of debris landform formation using a fuzzy set model as a mathematical data integration method. The first step was to obtain information about the location of debris landforms and their related factors. This information was verified through field observation and then used to build a database. In the second step, we conducted the fuzzy set modeling to generate a map, which classified the study area based on the possibility of debris formation. We then applied a cross-validation technique in order to evaluate the map. For a quantitative analysis, the calculated potential rate of debris formation was evaluated by plotting SRC(Success Rate Curve) and calculating AUC(Area Under the Curve). The prediction accuracy of the model was found to be 83.1%. We posit that the model is accurate and reliable enough to contribute to efficient field investigation and debris landform management.