• Title/Summary/Keyword: p-53

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Lysophosphatidic Acid Inhibits Nitric Oxide-induced Apoptosis via p70S6kinase Pathway in Rabbit Articular Chondrocytes

  • Yu, Seon-Mi;Kim, Song-Ja
    • Biomedical Science Letters
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    • v.15 no.4
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    • pp.349-353
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    • 2009
  • Lysophosphatidic Acid (LPA) is a bioactive lysophospholipid that is a potent signaling molecule able to provoke a variety of cellular responses in many cell types such as differentiation, inflammation and apoptosis. In this study, we have investigated the effect of LPA on Nitric oxide (NO)-induced apoptosis in rabbit articular chondrocytes. LPA dramatically reduced NO induced apoptosis of chondrocytes determined by phase contrast microscope and MTT assay. When chondrocytes alone treated with LPA, LPA induced phosphorylation of p70S6kinase, a serine/threonine kinase that acts downstream of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphoinositide-dependent kinase-1 (PDK-1) in the PI3 kinase pathway, dose-dependently detected by Western blot analysis. Phosphorylation of p70S6k with LPA was reduced expression of p53 in NO-induced apoptosis of chondrocytes. Also, inhibition of p70S6kinase with rapamycin was enhanced expression of p53 in chondrocytes. Our findings collectively suggest that LPA regulates NO induced apoptosis through p70S6kinase pathway in rabbit articular chondrocytes.

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Influence of the Job Stress, Resilience, and Professional Identity on Burnout in Operation Room Nurses (수술실 간호사의 직무스트레스, 회복탄력성, 전문직 정체성이 소진에 미치는 영향)

  • Lim, Eun Jin;Lee, Yun Mi
    • Journal of Korean Critical Care Nursing
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    • v.10 no.1
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    • pp.31-40
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    • 2017
  • Purpose: The purpose of this study was to identify the factors influencing on burnout in operating room nurses. Methods: Using a cross-sectional design, a total of 109 operating room nurses working at 7 general hospitals with 300 beds or more in B city were analyzed. The instruments used for this study assessed job stress, resilience, professional identity, and burnout. Data was analyzed using descriptive statistics, a t-test, an ANOVA, a Pearson's correlation coefficient and a multiple regression analysis. Results: There was a statistically significant correlation between burnout and job stress (r=.53, p<.001), resilience (r=-.59, p<.001), and professional identity (r=-.47, p<.001). The factors influencing burnout include job stress (${\beta}=.27$, p<.001), resilience(${\beta}=-.37$, p<.001), dissatisfaction with the nursing job (${\beta}=.32$, p<.001), and moderate satisfaction with the nursing job (${\beta}=.19$, p=.014), and the explanatory power was 53.0%. Conclusions: The results suggest that intervention to reduce job stress and to improve resilience, which were the factors influencing burnout in operating room nurses, is necessary.

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Mechanism of the Hydrolysis of 2-Phenyl-4H,5H,6H-3-methyl-3-thiazinium Perchlorate Derivatives

  • 김태린;이소영;변상용;김주창;한만소
    • Bulletin of the Korean Chemical Society
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    • v.20 no.10
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    • pp.1213-1217
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    • 1999
  • Hydrolysis reactions of 2-phenyl-4H,5H,6H-3-methyl-3-thiazinium perchlorate (PTP) and its derivatives at various pH have been investigated kinetically. The hydrolysis is quantitative, producing N-3-mercaptopropyl-N-methylbenzamide as the only product in the all pH ranges. The observed rate of hydrolysis of PTP was always of the first-order. For hydrolysis from PTP, Hammett ρvalues were 0.53, 0.84 and 1.13 for pH 5.0, 8.0, and 10.0, respectively. Bronsted βvalue was 0.53 for general base catalysis. This reaction is catalyzed by general w acetate concentration. However, as the amount of base becomes larger, the rate of hydrolysis reaction approaches the limiting values. The plot of log k vs. pH shows that the rate constants (kt) are two different regions in the profile; one part is directly proportional to hydroxide ion concentration and the other is not. On the bases of these result, the plausible hydrolysis mechanism and a reaction equation were proposed: Below pH 4.5, the hydrolysis was initiated by the addition of water to α-carbon. Above pH 9.0, the hydrolysis was proceeded by the addition of hydroxide ion to α-carbon. However, in the range of pH 4.5-8.0, these two reactions occured competitively.

Structural Characterization of Mouse HAUSP, a Proteolysis Regulator of p53

  • Lee, Hye-Jin;Yoo, Kyong-Jai;Baek, Kwang-Hyun
    • Animal cells and systems
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    • v.8 no.3
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    • pp.205-212
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    • 2004
  • The tumor suppressor protein p53 is stabilized by the herpes-virus-associated ubiquitin-specific protease (HAUSP), a deubiquitinating enzyme. We previously isolated and characterized a mouse orthologue of HAUSP, mHAUSP. mHAUSP cDNA consisted of 3,312 bp encodes 1,103 amino acids with a molecular weight of approximately 135 kDa containing highly conserved Cys, Asp (I), His, and Asn/Asp (II) domains. In this study, we carried out site-directed mutagenesis of 6 conserved amino acids (Cys224, Gln231, Asp296, His457, His465, and Asp482) in Cys box, QQD box, and His box. Interestingly, the conserved Gln 231 was not essential for the catalytic activity of mHAUSP. However, the other conserved amino acids were required for deubiquitinating activity of mHAUSP. We performed isopeptidase assay and confirmed that mHAUSP is able to remove ubiquitin from ubiquitinated substrates. In addition, we observed that mHAUSP induces apoptosis in HeLa cells.

Effect of Carcinogenic Chromium(VI) on Cell Death and Cell Cycle in Chinese Hamster Ovary Cells

  • Lee, San-Han;Nam, Hae-Seon;Kim, Sung-Ho
    • Environmental Mutagens and Carcinogens
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    • v.24 no.3
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    • pp.113-120
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    • 2004
  • Chromium compounds are known human and animal carcinogens. In this study, the effects of sodium chromate on apoptosis and cell cycle were investigated in order to unveil the elements of early cellular responses to the metal. Using Chinese hamster ovary cells(CHO-K1-BH4), we found taht chromium (VI) treatment induced apoptosis in these cells, as signified by nuclear fragmentation, DNA laddering on agarose gel electrophoresis, and an increased proportionof cells with hypodiploid DNA. Preceding these changes, chromium (VI) treatment increased caspase 3 pritease activity and also increased expression of p53 protein, while the level of bcl2 protein was not changed. Coincubation with caspase inhibitor, Z-DEVD-FMK, inhibited chromium-induced apoptosis. In the flow cytometric analysis using propidium iodide fluorescence, an increase of cell population in G2/M phase was shown in cells exposed to at least 160 $\mu\textrm{m}$ of sodium chromate for 72h, form 9.8% for 0$\mu\textrm{m}$ chromium (VI) to 26.4% for 320$\mu\textrm{m}$ chromium(VI). Taken together, these findings suggest that chromium(VI)-induced apoptosis is accompanied by G2/M cell cycle arrest, and that p53-mediated pathway may be involved in positive regulation of G2/M arrest and a concurred apoptosis in CHO cells.

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A Study on the Growth of $In_{0.53}Ga_{0.47}As/In_{0.52}AI_{0.48}$As/InP Epitaxial Layers for HEMT by MBE (MBE에 의한 HEMT 소자용 $In_{0.53}Ga_{0.47}As/In_{0.52}AI_{0.48}$As/InP 에피택셜층 성장 연구)

  • 노동완;이해권;이재진;이재진;편광의;남기수
    • Journal of the Korean Vacuum Society
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    • v.4 no.2
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    • pp.177-182
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    • 1995
  • 저잡음 HEMT소자 제작을 위한 에피택셜 기판을 MBE방법을 이용하여 $In_{0.53}Ga_{0.47}As/In_{0.52}AI_{0.48}$As/InP 물질계로 성장하였다. 기판온도의 변화, 채널층과 격리층 사이의 성장 일시 멈춤 등의 성장 조건 변화에 따른 Hall 이동도의 변화를 연구하였다. 전자 공급층을 Si으로 델타도핑한 결과 같은 조건에서 성장기판의 온도를 $520^{\circ}C$에서$ 540^{\circ}C$로 증가시키면 실온의 전자이동도는 7,850$\textrm{cm}^2$/Vsec으로 증가하였으며, 격리층과 채널층 사이에서 약 50초간 성장중 채널층의 표면 adatom의 surface migration 시간을 충분히 제공하여 결정결함의 감소로 계면의 급격성이 향상된 결과로 사료된다. 본 실험을 통하여 얻은 최고 이동도 값은 격리층의 두께가 $100\AA$인 경유에 상온 측정결과 $11,400\textrm{cm}^2$/vsec 및 77K 측정결과 $50,300\textrm{cm}^2$/Vsec이었다.

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Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model

  • Keum, Dong In;Pi, Long-Quan;Hwang, Sungjoo Tommy;Lee, Won-Soo
    • Journal of Ginseng Research
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    • v.40 no.2
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    • pp.169-175
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    • 2016
  • Background: Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. Methods: We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). Results: 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Conclusion: Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression.

Effect of Orostachys japonicus A. Berger on Apoptosis Induction of Human Leukemia HL60 Cells (와송의 HL60백혈병세포의 Apoptosis유도 효과)

  • Oh, Chan-Ho;Bae, Jin-Beom;Kim, Nam-Seok;Jeon, Hoon;Han, Kwang-Soo;Lee, Moon-Jun;Kwon, Jin
    • Korean Journal of Pharmacognosy
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    • v.40 no.2
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    • pp.118-122
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    • 2009
  • Methanol extracts of Orostachys japonicus A. Berger (OAB) were found to exhibit apoptosis induction of HL60 human acute promyelocytic leukemia cells. Treatment of OAB exerted strong cytotoxicity against HL60 cells. OAB induced DNA fragmentation of HL60 cells in a dose dependent manner. Nitric oxide production were also increased in OAB-treated RAW264.7 macrophage cell lines. Treatment of OAB increased the expression of p53 and iNOS gene and the expression of p53, $NF-{\kappa}B$ and iNOS protein in cultured HL60 and RAW264.7 cells. These results suggest that OAB are effective on strong anti-cancer properties and can be useful as a chemo-preventive agents.

Elucidating Molecular Interactions of Natural Inhibitors with HPV-16 E6 Oncoprotein through Docking Analysis

  • Kumar, Satish;Jena, Lingaraja;Galande, Sneha;Daf, Sangeeta;Mohod, Kanchan;Varma, Ashok K.
    • Genomics & Informatics
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    • v.12 no.2
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    • pp.64-70
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    • 2014
  • Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

Structural and Thermodynamic Characteristics of cHLH Peptide and cHLH/HDM2 Complex

  • Im, Haeri;Cho, Sunhee;Ham, Sihyun
    • Proceeding of EDISON Challenge
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    • 2016.03a
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    • pp.62-66
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    • 2016
  • Tumor suppressor protein p53 loses its function upon binding with the HDM2 protein, and inhibiting the p53-HDM2 interaction is critical to suppress tumor cell growth. Recently, the cyclized helix-loop-helix peptide (cHLH) mimicking the ${\alpha}-helix$ part of the p53 protein has been designed and found to exhibit high binding affinity with HDM2. Here, we report the structural and thermodynamic characteristics of the bound complex of the cHLH peptide with the HDM2 protein. We performed molecular dynamics simulations to investigate the structural features of the cHLH peptide as well as its complex with the HDM2. The binding free energy calculation based on the integral equation theory was also executed to quantify the binding affinity for the cHLH/HDM2 complex and to understand the factors contributing to the binding affinity. We found a variety of factors for the helix stability of the cHLH peptide as well as in the complexation with the HDM2, which may provide an insight into the development of anti-cancer drug designs.

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