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      • KCI등재

        15세기 보허자 음악 복원 연구

        문숙희(Moon, Sukhie) 숭실대학교 한국문학과예술연구소 2020 한국문학과 예술 Vol.36 No.-

        본고에서는 『악학궤범』에 전해지는 15세기 궁중공연문화 중 ‘학무(鶴舞)’를 재연하기 위해 그 반주음악인 15세기 보허자의 리듬을 확인하고, 그 음악을 복원해보았다. 그 결과는 다음과 같다. 15세기 보허자의 리듬은 8/4박자로서13-14세기 보허자 4/4박자의 ½박(분박♪)이 이분박 한 박(♩)으로 확대된 것이다. 16세기에는 15세기 보허자의 ½박(분박)이 삼분박 한 박(♩.)으로 확대되어, 16세기에는 삼분박 4박자(12/8, 4/♩.)가 되었다. 17세기에는 16세기의 ⅓박(분박)이 삼분박 한 박(♩.)으로 확대되어, 16세기의 삼분박 한 박(♩.=♪♪♪)이 3박자 한 마디(♩.♩.♩.)로 되었다. 18세기에는3박자한마디가5박자한마디로확대되었고, 19세기에는5박자 한 마디가 10박자 한 마디로 확대되었다. 17세기 보허자의 리듬은 오늘날 밑도드리에서, 18세기와 19세기 보허자의 리듬은 오늘날 보허사에서 확인할 수 있다. 15세기 보허자 선율은 16세기 보허자에서 추적해냈다. 16세기 보허자와 15세기 보허자의 관계는 다음과 같다. 첫째, 16세기 삼분박 한 박(♩.)은 15세기의 ½박(분박♪)에 해당된다. 둘째, 16세기삼분박한박중첫음은대부분15세기의½박(분박) 음과같으나, 드물게 둘째 또는 셋째 음이 15세기 ½박(분박) 음이 되기도 한다. 셋째, 15세기 보허자의 선율과 종지형은 중국에서 온 당악을 따랐다. This paper restores the rhythm and melody of the 15<SUP>th</SUP> century Boheoja, the accompaniment music for “hakmu(鶴舞)” dance recorded in Akhak-gaebeom. The results are as follows. The rhythm of the 15<SUP>th</SUP> century Boheoja was 8/4, and it is the one expanded from the 4/4 rhythm of the 13-14<SUP>th</SUP> centuries Boheoja by expanding one half beat(♪) to one beat(♩). The rhythm of the 15<SUP>th</SUP> century Boheoja became the 12/8(4/♩.) rhythm of the 16<SUP>th</SUP> century by expanding one half beat(♪) to one ternary subdivided beat(♩.). In the 17<SUP>th</SUP> century, one ternary subdivided beat(♩.=♪♪♪) was expanded to a measure of 3 beats (♩.♩.♩.) by expanding one third beat(♪) to one ternary subdivided beat(♩.). In the 18<SUP>th</SUP> century, a measure of 3 beats was expanded to a measure of 5 beats, and in the 19<SUP>th</SUP> century, a measure of 5 beats was expanded to a measure of 10 beats. The rhythm of the 17<SUP>th</SUP> century Boheoja can be found in today’s Mitdodri and the rhythm of the 18<SUP>th</SUP> centuries Boheoja and the 19<SUP>th</SUP> centuries Boheoja can be found in today’s Boheosa. The 15<SUP>th</SUP> century Boheoja melody was traced from the 16<SUP>th</SUP> century Boheoja. The relationship between the 15<SUP>th</SUP> century Boheoja and the 16<SUP>th</SUP> century Boheoja is as follows. Firstly, the 16<SUP>th</SUP> century’s ternary subdivided beat corresponds to the 15<SUP>th</SUP> century’s half beat. Secondly, the first note of the 16<SUP>th</SUP> century’s ternary subdivided beat is mostly the note of the 15<SUP>th</SUP> century’s half beat, but the second or third note of the 16<SUP>th</SUP> century’s beat can also become that of the 15<SUP>th</SUP> century’s half beat. Thirdly, the cadence and melody of the 15<SUP>th</SUP> century Boheoja followed Tangak which came from China.

      • KCI등재

        15-Deoxy-Δ12,14-prostaglandin J2 Upregulates the Expression of 15-Hydroxyprostaglandin Dehydrogenase by Inducing AP-1 Activation and Heme Oxygenase-1 Expression in Human Colon Cancer Cells

        박종민,나혜경 대한암예방학회 2019 Journal of cancer prevention Vol.24 No.3

        Background: Abnormal upregulation of prostaglandin E2 (PGE2) is considered to be a key oncogenic event in the development and progression of inflammation-associated human colon cancer. It has been reported that 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme catabolizing PGE2, is ubiquitously downregulated in human colon cancer. 15-Deoxy-12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor  ligand, has been shown to have anticarcinogenic activities. In this study, we investigate the effect of 15d-PGJ2 on expression of 15-PGDH in human colon cancer HCT116 cells. Methods: HCT116 cells were treated with 15d-PGJ2 analysis. The expression of 15-PGDH in the treated cells was measured by Western blot analysis and RT-PCR. In addition, the cells were subjected to a 15-PGDH activity assay. To determine which transcription factor(s) and signaling pathway(s) are involved in 15d-PGJ2-induced 15-PGDH expression, we performed a cDNA microarray analysis of 15d-PGJ2-treated cells. The DNA binding activity of AP-1 was measured by an electrophoretic mobility shift assay. To determine whether the AP-1 plays an important role in the 15d-PGJ2-induced 15-PGDH expression, the cells were transfected with siRNA of c-Jun, a major subunit of AP-1. To elucidate the upstream signaling pathways involved in AP-1 activation by 15d-PGJ2, we examined its effect on phosphorylation of Akt by Western blot analysis in the presence or absence of kinase inhibitor. Results: 15d-PGJ2 (10 M) significantly upregulated 15-PGDH expression at the mRNA and protein levels in HCT-116 cells. 15-PGDH activity was also elevated by 15d-PGJ2. We observed that genes encoding C/EBP delta, FOS-like antigen 1, c-Jun, and heme oxygenase-1 (HO-1) were most highly induced in the HCT116 cells following 15d-PGJ2 treatment. 15d-PGJ2 increased the DNA binding activity of AP-1. Moreover, transfection with specific siRNA against c-Jun significantly reduced 15-PGDH expression induced by 15d-PGJ2. 15d-PGJ2 activates Akt and a pharmacological inhibitor of Akt, LY294002, abrogated 15d-PGJ2-induced 15-PGDH expression. We also observed that an inhibitor of HO-1, zinc protoporphyrin IX, also abrogated upregulation of 15-PGDH and down-regulation of cyclooxygenase-2 expression induced by 15d-PGJ2. Conclusions: These finding suggest that 15d-PGJ2 upregulates the expression of 15-PGDH through AP-1 activation in colon cancer HCT116 cells. (J Cancer Prev 2019;24:183-191)

      • Upregulation of MIP‐2 (CXCL2) expression by 15‐deoxy‐Δ<sup>12,14</sup>‐prostaglandin J<sub>2</sub> in mouse peritoneal macrophages

        Kim, Hyo Y,Kim, Hee S Nature Publishing Group 2007 Immunology and cell biology Vol.85 No.1

        <P>A peroxisome proliferator‐activated receptor <I>γ</I> (PPAR<I>γ</I>) ligand, 15‐deoxy‐Δ<SUP>12,14</SUP>‐prostaglandin J<SUB>2</SUB> (15d‐PGJ<SUB>2</SUB>), has been reported to possess anti‐inflammatory activity in activated monocytes/macrophages. In this study, we investigated the effect of 15d‐PGJ<SUB>2</SUB> on the lipopolysaccharide (LPS)‐induced expression of chemokine mRNAs, especially macrophage inhibitory protein (MIP)‐2 (CXCL2), in mouse peritoneal macrophages. The inhibitory actions of the natural PPAR<I>γ</I> ligands, 15d‐PGJ<SUB>2</SUB> and prostaglandin A1 (PGA1), on the expression of RANTES (regulated upon activation, normal T expressed and secreted; CCL5), MIP‐1<I>β</I> (CCL4), MIP‐1<I>α</I> (CCL3), IFN‐<I>γ</I>‐inducible protein 10 kilodaltons (IP‐10; CXCL10) and monocyte chemoattractant protein‐1 (MCP‐1; CCL2) mRNA in LPS‐treated cells were stronger than those of the synthetic PPAR<I>γ</I> ligands troglitazone and ciglitazone. However, 15d‐PGJ<SUB>2</SUB> enhanced the expression of LPS‐induced MIP‐2 (CXCL2) mRNA. A specific PPAR<I>γ</I> antagonist (GW9662) had no effect on the inhibitory action of 15d‐PGJ<SUB>2</SUB> and PGA1 in LPS‐induced chemokine mRNA expression and on the synergistic action of 15d‐PGJ<SUB>2</SUB> in LPS‐induced MIP‐2 (CXCL2) expression. Moreover, LPS itself reduced the expression of PPAR<I>γ</I>. Although the synergistic effect of 15d‐PGJ<SUB>2</SUB> on LPS‐induced MIP‐2 (CXCL2) mRNA expression was remarkable, the production of MIP‐2 (CXCL2) in cells treated with 15d‐PGJ<SUB>2</SUB> and LPS did not increase compared to the production in cells treated with LPS alone. The synergistic action of 15d‐PGJ<SUB>2</SUB> on LPS‐induced MIP‐2 (CXCL2) mRNA expression was dependent on the activation of nuclear factor‐<I>κ</I>B (NF‐<I>κ</I>B), and 15d‐PGJ<SUB>2</SUB> increased the phosphorylation of p38 and stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) in cells stimulated with LPS. These results suggest that the synergistic effect of 15d‐PGJ<SUB>2</SUB> on LPS‐induced MIP‐2 (CXCL2) expression is PPAR<I>γ</I>‐independent, and is mediated by the p38 and SAPK/JNK pathway in mitogen‐activated protein kinase signaling pathways, which activates NF‐<I>κ</I>B. Our data may give more insights into the different mechanisms contrary to the anti‐inflammatory effect of 15d‐PGJ<SUB>2</SUB> on the expression of chemokine genes.</P>

      • SCOPUSKCI등재

        IgA 신병증에서 15-Deoxy-Delta(12,14)-Prostaglandin J2 및 염증성 사이토카인의 역할

        정유석 ( You Seok Jeong ),송상헌 ( Sang Heon Song ),이동원 ( Dong Won Lee ),이수봉 ( Soo Bong Lee ),양병윤 ( Byeong Yun Yang ),곽임수 ( Ihm Soo Kwak ) 대한신장학회 2008 Kidney Research and Clinical Practice Vol.27 No.3

        목적: 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2)은 prostaglandin D2 대사로부터 생성되며 PPAR-γ의 내인성 ligand로 알려져 있다. 또한, 여러 연구에서 15d-PGJ2의 항염증 효과에 대해 보고하고 있다. 최근 다양한 원인에 의한 신손상에 복잡한 염증작용이 관여하고 있으며 이에 대한 연구가 증가하고 있는 추세이다. 본 연구에서는 IgA 신병증에서 15d-PGJ2가 염증 조절자로서 역할을 할 것으로 가정하고 다른 염증성 사이토카인과 비교 연구함으로써 그 역할을 구명하고자 하였다. 또한 최근 제안된 IgA 신병증에서의 예후점수와 단백뇨간의 상관관계 분석 및 미세변화신증과의 비교를 해보고자 하였다. 방법: 신조직 검사로 확진된 54명의 IgA 신병증 환자와 5명의 미세변화신증 환자를 대상으로 하였다. 신조직에 대해 PPAR-γ 단클론 항체를 이용하여 면역조직화학 염색을 시행하였고 신조직 당일에 CRP를 포함한 혈청 검사와 수집된 검체를 이용하여 요중 IL-6, IL-23, TGF-β1, 15d-PGJ2를 측정하였다. 결과: 신조직의 PPAR-γ 양성군과 음성군간에 염증성 사이토카인과 CRP, 15d-PGJ2의 차이는 없었다. 15d-PGJ2와 염증성 사이토카인 및 CRP와의 상관관계에서는 15d-PGJ2가 IL-23 (r=-0.293 p=0.0311), TGF-β1 (r=-0.427, p<0.001), CRP (r=-0.444, p<0.001)와 음의 상관관계가 있었으며 CRP와 염증성 사이토카인 사이에는 IL-23와 CRP 사이를 제외하고는 모두에서 양의 상관관계가 있었다. 신증후군 수준의 단백뇨를 보이는 IgA 신병증군에서 단백뇨가 없는 군에 비해 요중 TGF-β1 배설이 많았으나 다중회귀분석에서는 TGF-β1와 단백뇨 사이의 관련성은 없었다. 염증성 사이토카인과 CRP는 예후점수와 양의 상관관계가 있었으며 15d-PGJ2는 예후점수와 음의 상관관계가 있었다. 다중회귀분석에서 CRP와 15d-PGJ2, 24시간 단백뇨가 예후점수에 영향을 주었으며 24시간 단백뇨에 영향을 주는 인자는 15d-PGJ2 뿐이었다. 미세변화신증과의 비교에서는 염증성 사이토카인 및 CRP는 양군에서 차이가 없었으며 15d-PGJ2가 IgA 신병증에서 미세변화신증에 비해 높았다. 결론: 내인성 15d-PGJ2는 IgA 신병증에서 염증작용과 관련이 있었으며 예후점수와 단백뇨와의 관련성에 근거하여 신손상을 줄여 줄 수 있는 인자로서 고려해 볼 수 있겠다. 향후 더 많은 환자의 추적 관찰을 통해 15d-PGJ2의 역할에 대한 연구가 필요할 것으로 판단한다. Purpose: This study was performed to demonstrate a correlation among urinary 15d-PGJ2, proinflammatory cytokines (i.e. IL-23, IL-6, and TGF-β1), and CRP, and to determinate the contributors to prognostic score and proteinuria in IgAN patients. Methods: Fifty-four patients with biopsy-proven IgAN were enrolled. For comparison with IgAN, five MCD patients were also enrolled. Immunohistochemical staining for PPAR-γ in kidney tissue and measurements of urinary IL-6, IL-23, TGF-β1, 15d-PGJ2 and serum CRP were performed. Results: There was no difference according to PPAR-γ staining. 15d-PGJ2 was negatively correlated with urinary IL-23, TGF-β1, and CRP. Among proinflammatory cytokines and CRP, there were positive relationships with each other except for IL-23 and CRP. TGF-β1 in the group having proteinuria more than 3 g/day was statistically higher than that in the sole hematuria group. However, in multivariate regression analysis, not a single relation was found between TGF-β1 and proteinuria. Prognostic score was correlated with IL-6, IL-23, TGF-β1, CRP, 15d-PGJ2, and 24hr proteinuria. 24hr proteinuria was correlated with IL-6 and 15d-PGJ2. In multivariate regression analysis, CRP, 15d-PGJ2, and 24hr proteinuria contributed to prognostic score, and only 15d-PGJ2 contributed to 24hr proteinuria. Last, urinary 15d-PGJ2 in IgAN was higher than that in MCD. Conclusion: Endogenous 15d-PGJ2 was associated with inflammation and might be considered as a material which could delay the damage of kidney in IgAN. In the future, larger cohort and long-term follow-up studies are needed to demonstrate the role of 15d-PGJ2 as prognostic indicator or marker of kidney damage.

      • KCI등재

        15세기 의존명사 목록의 재검토

        서정호(Seo, Jeong Ho) 동악어문학회 2018 동악어문학 Vol.76 No.-

        본고에서는 중세국어의 의존명사에 대한 선행 연구들의 목록이 각각 다르다는 점에 주목하여, 중세국어의 의존명사 목록의 객관성에 대한 의문을 제기하였다. 먼저 여러 선행 연구들 중에서 5개의 선행 연구를 선정하여, 해당 연구들의 의존명사 목록을 정리하고, 정리된 선행 연구들의 의존명사 목록 중에서 ‘수 단위 의존명사, 한자로 나타나는 의존명사, 15세기에 나타나지 않는 의존명사’를 제외하여, 본고에서 살필 15세기를 중심으로 한 의존명사 목록을 작성하였다. 다음으로 본고에서 살필 15세기 의존명사 목록을 고영근(1982)을 기준으로 정리하고, 각 논의에서 분류된 의존명사들을 빈도순으로 분류하였다. 빈도순으로 분류한 15세기의 의존명사들 중에서, 하나의 선행 연구에서만 의존명사로 인정한 ‘겿, 놈, 단, 달, 다시/드시/디시, 다비, 대로, 뎌에, 디4, 살, 새, 시, 억, 이어긔, 젼차 , 직’에 대하여 해당 형태들의 의존명사 여부를 확인하였다. 그 결과, 본고에서는 ‘겿, 놈, 직’은 15세기의 의존명사로 보았다. 하지만 ‘다시/드시/디시’는 의존명사와 접미사가 결합한 형태로 보고, ‘단, 달, 대로, 디4, 살, 시’는 의존명사와 조사가 결합한 형태로 보고, ‘새’는 통합형 어미에 포함된 형태로 보며, ‘젼차’는 자립명사로 보고, ‘다비’는 파생부사 또는 용언의 활용형으로 보고, ‘뎌에’는 명사구와 격조사가 결합한 형태로 보며, ‘이어긔’는 부사로 보아, 해당 형태들을 15세기의 의존명사로 보지 않았다. 그리고 ‘억’은 관형사가 선행하고 조사가 후행하는 구성에 쓰이는 의존명사일 가능성이 있으나, 의존명사보다 조사와 관련된 형태로 볼 근거가 더 많다고 판단하여, 해당 형태도 15세기의 의존명사로 보지 않았다. In this paper, attention was drawn to the objectivity of the bound noun list of medieval languages, noting that the list of preceding researches about bound nouns of medieval language was different. First, five prior researches were selected among the various preceding researches, and a list of bound nouns. We exclude ‘number unit bound nouns, bound nouns appearing in Chinese characters, and bound nouns not appearing in the 15th century’ from the list of bound nouns in the preceding researches, and have made a list of bound nouns centering around the 15th century. Next, the list of bound nouns in the 15th century is summarized by Ko Young Keun(1982), and the bound nouns classified in each discussion are classified in frequency order. Among bound nouns of the 15th century classified by frequency, it was confirmed whether or not bound nouns of the corresponding forms were recognized for ‘겿, 놈, 단, 달, 다시/드시/디시, 다비, 대로, 뎌에, 디4, 살, 새, 시, 억, 이어긔, 젼차, 직’ recognized as bound nouns in only one preceding research. As a result, in this paper, ‘겿, 놈, 직’ are seen as bound nouns of the 15th century. But, ‘다시/드시/디시’ are seen as a combination of bound noun and suffix, ‘단, 달, 대로, 디4, 살, 시’ are seen as a combination of bound noun and postposition, ‘새’ is included in the compound ending, ‘젼차’ is regarded as independent noun, ‘다비’ is regarded as derived adverb or inflectional form of verb, ‘뎌에’ is,regarded as a combination of noun phrase and case, ‘이어긔’ is regaded as adverb, did not regard the forms as bound nouns of the 15th century. And ‘억’ is considered to be a bound noun that is used in conposition of precedent adnominal followed by postposition, but in the 15th century it was not regarded as a bound noun, because it was more likely to see it as a form related to case than a bound noun.

      • GDF-15 Levels Predict Efficacy in Lung Cancer Patients Treated with PD-1/ PD-L1 Inhibitors

        ( Da Hyun Kang ),( Pureum Sun ),( Chaeuk Chung ),( Song-i Lee ),( Dongil Park ),( Jeong Suk Koh ),( Yoonjoo Kim ),( Jeong Eun Lee ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0

        Background Growth and differentiation factor 15 (GDF-15) is a divergent member of the TGF-β superfamily. In disease states, such as acute injury, inflammation, and cancer, GDF-15 expression is dramatically increased. In cancer patients, elevated GDF-15 levels correlate with poor prognosis. In this study, we investigated whether GDF-15 levels can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. Methods This study included patients who were diagnosed with NSCLC and treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital from March 2018 to May 2020. We evaluated plasma GDF-15 levels and correlated the findings with clinical outcomes. Results In our cohort of 89 NSCLC patients, the mean plasma GDF-15 levels were 2475.86 pg/mL (794.07-4901.25). The objective response rate (ORR) was significantly higher in those with low GDF-15 (<1520 pg/mL) than those with high GDF-15 (ORR 35.5% vs. 15.5%, p=0.032). In 47 patients with blood sample post 2 months after treatment, the ORR and disease control rate (DCR) were significantly higher in patients with decreased GDF-15 levels compared to those with increased follow up GDF-15 levels (ORR 26.7% vs. 5.9%, p=0.028; DCR 73.3% vs. 35.3%, p=0.011). Conclusion Plasma GDF-15 levels could be a potential biomarker for predicting the efficacy in NSCLC patients treated with PD-1/PD-L1 inhibitors.

      • KCI등재

        15-Deoxy-Δ12,14-Prostaglandin J2 Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

        김정혜,김희선 대한면역학회 2009 Immune Network Vol.9 No.2

        Background: 15d-PGJ2 has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-PGJ2 on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-κB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-PGJ2 decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ2 in SHR VSMCs was mediated through PPARγ, and dependent on NF-κB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 on LPSinduced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ2/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARγ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/ LPS-induced IL-8/CXCL8 expression in SHR VSMCs. Background: 15d-PGJ2 has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-PGJ2 on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-κB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-PGJ2 decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ2 in SHR VSMCs was mediated through PPARγ, and dependent on NF-κB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 on LPSinduced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ2/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARγ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/ LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

      • SCISCIESCOPUS

        15-Deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> activates PI3K-Akt signaling in human breast cancer cells through covalent modification of the tumor suppressor PTEN at cysteine 136

        Suh, Jinyoung,Kim, Do-Hee,Kim, Eun-Hee,Park, Sin-Aye,Park, Jong-Min,Jang, Jeong-Hoon,Kim, Su-Jung,Na, Hye-Kyung,Kim, Nam-Doo,Kim, Nam-Jung,Suh, Young Ger,Surh, Young-Joon Elsevier 2018 Cancer letters Vol.424 No.-

        <P><B>Abstract</B></P> <P>15-Deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> (15d-PGJ<SUB>2</SUB>), one of the terminal products of cyclooxygenase-2-catalized arachidonic acid metabolism, has been shown to stimulate breast cancer cell proliferation and migration through Akt activation, but the underlying mechanisms remain poorly understood. In the present study, we investigated the effects of 15d-PGJ<SUB>2</SUB> on the activity of PTEN, the inhibitor of the phosphoinositide 3-kinase (PI3K)-Akt axis, in human breast cancer (MCF-7) cells. Since the α,β-unsaturated carbonyl moiety in the cyclopentenone ring of 15d-PGJ<SUB>2</SUB> is electrophilic, we hypothesized that 15d-PGJ<SUB>2</SUB>-induced Akt phosphorylation might result from the covalent modification and subsequent inactivation of PTEN that has several critical cysteine residues. When treated to MCF-7 cells, 15d-PGJ<SUB>2</SUB> bound to PTEN, and this was abolished in the presence of the thiol-reducing agent dithiothreitol. A mass spectrometric analysis by using recombinant and endogenous PTEN protein revealed that the cysteine 136 residue (Cys<SUP>136</SUP>) of PTEN is covalently modified upon treatment with 15d-PGJ<SUB>2</SUB>. Notably, the ability of 15d-PGJ<SUB>2</SUB> to covalently bind to PTEN as well as to induce Akt phosphorylation was abolished in the cells expressing a mutant form of PTEN in which Cys<SUP>136</SUP> was replaced by serine (C136S-PTEN). The present study demonstrates for the first time that electrophilic 15d-PGJ<SUB>2</SUB> directly binds to cysteine 136 of PTEN and provides new insight into PTEN loss in cancer progression associated with chronic inflammation. These observations suggest that 15d-PGJ<SUB>2</SUB> can undergo nucleophilic addition to PTEN, presumably at Cys<SUP>136</SUP>, thereby inactivating this tumor suppressor protein with concomitant Akt activation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PTEN is inactivated through covalent modification by 15-deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> in breast cancer MCF-7 cells. </LI> <LI> 15-Deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> directly binds to the cysteine 136 residue of the recombinant PTEN. </LI> <LI> PTEN interaction with 15-deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> stimulates Akt phosphorylation. </LI> <LI> 15-Deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> stimulates growth of MDA-MB-231 cells when inoculated to the athymic nude mice. </LI> </UL> </P>

      • KCI등재

        15세기 북방정세와 明의 邊境政策의 再檢討

        남의현(Nam Eui-Hyeon) 강원대학교 인문과학연구소 2011 인문과학연구 Vol.0 No.29

        15세기는 明나라가 대외팽창을 시도하면서 시작되었다. 그런 의미에서 15세기를 이야기 할 때 중국의 관점을 자신도 모르게 수용하며 明나라의 팽창에 의해 북방의 몽골 세력이 상당히 약화된 것으로 이해하였다. 더구나 明나라의 역사에 가려 몽골의 역사가 주요한 무대에서 완전히 사라졌다고 인식하기도 하였다. 그러나 몽골인이 연구한 몽골사를 읽어보면 결코 그렇지 않다는 사실을 여러 곳에서 확인할 수 있다. 명나라 永樂帝는 15세기 靖難의 變을 통해 정권을 차지하면서 그의 통치시기(1403~1424)동안 몽골과 만주로의 진출을 도모하였다. 鄭和出使와 같은 해양진출을 시도하는 동시에, 5차 몽골친정, 遼東都司의 정비와 奴兒干都司의 설치를 통한 요동지배와 팽창시도, 여진을 관할하기 위한 衛所 설치 등은 명나라가 역동적인 15세기를 만들어 가려는 모습으로 평가할 수도 있을 것이다. 그러나 15세기 초기를 화려하게 장식했던 영락제의 변경정책은 그의 사후 지속될 수 없었고 그에 대한 평가에서도 그리 성공적이지 못했다. 그의 사후 명나라의 변경 정책은 공세에서 수세로 전환하였고 이후 어느 황제도 더 이상 역동적인 팽창을 시도할 수 없었다. 수세적인 방어로의 전환은 북방민족에 대한 완벽한 대응책이 될 수 없었다. 인구의 유출과 군사들의 도망과 반란 등으로 명나라는 오히려 북부의 몽골과 동쪽 여진의 성장에 의해 수세에 몰리는 상황이 변경에서 전개되면서 만리장성과 요동변장의 수축이라는 방어벽 축조로 이어졌다. 그런 의미에서 15세기는 새롭게 평가되어야 하는 것이다. 15세기 명나라는 새로운 동아시아 국제질서를 만들려는 가장 왕성한 시도로 시작되었지만 그리고 이를 통해 질서의 재편을 구상하였지만 결과적으로 지속시키지 못하고 좌절되었다고 평가할 수 있다. 이것은 앞으로 동아시아사 연구에서 15세기에 대한 평가가 ①명ㆍ몽골과 명ㆍ여진을 명과 종속관계에서 보았던 시각에 대한 재검토, ② 元ㆍ明 交替의 의미에 대한 재해석, ③ 조선과 여진관계의 재정립, ④조선과 명의 국경선과 국경지대에 대한 재설정 등 근세 동아시아 국제질서에 대한 새로운 역사상이 보편적이고 객관적 관점에서 재구성되는데 중요한 관점을 제공할 수 있다는 의미이기도 하다. The Ming dynasty in the 15th century attempted an expansionist policy. In that sense, the history of Ming in the 15th century was understood very dynamic that weakened northern tribes such as Mongolia. However, there is different perspective found from the history of Mongolia written by a Mongolian. Emperor Yong-le(永樂) usurped the power by coup through the upheaval of Jeongnan(靖難) in the 15th century and planned to expand and progress to Mongolia and Liaodong(遼東). Zheng He’s voyage, 5th Mongol conquest, Liaodongdusi(遼東都司) alignment, installment of Nuergandusi(奴兒干都司) and Jurchen Wiso(衛所) are some vibrant examples of Ming. However, such prosperous frontier policy by Yong-le(永樂) in the 15th century was not successful and could not continue thereafter. After his death, the frontier policy became defensive and no emperor could attempt dynamic expansion policy. Such transition from offence to defense could not be a perfect measurement against the northern tribes. Thanks to the release of population, flee of troops and riot, Ming became defensive by the growth of Mongolia in North and Jurchen in East. To conclude, although China argues that the 15th century was the most dynamic period to establish new international order by Ming to attempt to reorganize east Asia’s international order, the frontier policy of Ming began to be defensive from 15th century. It means the study on East Asia history, the historical image of 15th century’s East Asia’s international order should be reconsidered from universal and objective perspective.

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