• Title/Summary/Keyword: Cdc2

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Improved Axonal Regeneration Responses in the Injured Sciatic Nerve of Rats by Danggui Treatment (당귀가 rat의 손상된 좌골신경 재생에 미치는 영향)

  • Hong, Soon-Sung;Oh, Min-Seok
    • The Journal of Korean Medicine
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    • v.29 no.2
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    • pp.133-150
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    • 2008
  • Objective: This study was performed to examine Danggui (DG, Angelica gigas Nakai)'s potential activity for promoting axonal regeneration in the injured peripheral nerve. Methods: Using the sciatic nerve in the rats, DG extract 5 ${\mu}l$(10 mg/ml in 0.5% saline) was dripped into the injury site of the nerve. Results: DG treatment facilitated axonal elongation responses in the distal portion to the injury site. GAP-43 protein levels were upregulated by DG treatment in the injured nerve and also in the DRG, suggesting the induction of GAP-43 expression at gene expression level after nerve injury. Phospho-Erk1/2 protein levels were upregulated in the injured nerve area and also in the DRG, suggesting retrograde transport of phospho-Erk1/2 protein from the injury area to the cell body. Cdc2 protein levels were slightly upregulated by DG treatment. DG treatment increased the number of non-neuronal cells in the distal portion to the injury site. Conclusions: The present data suggest that DG is effective for enhanced axonal regrowth after sciatic nerve injury.

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RAS inhibitor를 이용한 항암제의 개발에 관하여

  • 어미숙
    • The Microorganisms and Industry
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    • v.19 no.4
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    • pp.32-35
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    • 1993
  • ras는 활성화 형태인 GTP bound form과 비활성화 형태인 GDP bound form의 두 형태로 존재하며 두 형태를 매개하는 regulatory protein들에 의해 그 activity가 조절된다. 또한 ras는 GTP와 GDP에 강한 친화성이 있으며 세포내에는 GTP보다 GDP가 더 많이 있어서 평소에는 ras가 GDP와 결합하고 있다가 활성화될때만 GTP와 결합하는 것으로 추정된다. GDP bound ras는 guanine nucloetide exchange protein(GEP)에 의해 활성화된 GTP bound form으로 전환되며 ras의 기능이 발휘된 후에는 GTPase activating protein(GAP)에 의해 비활성화된다. Yeast의 경우 IRA1과 2의 product가 GAP의 역할을 하는 것으로 알려져 있고 CDC25 gene의 product가 GEP의 기능을 담당하는 것으로 알려져 있다. NF1 gene은 Von Recklinghausen Neurofibromatosis Type I 질병을 가진 환자에게서 발견되었는데 부분적으로 sequencing한 결과에 따르면 yeast의 IRA1/2, mammalian GAP gene product와 protein homology가 높은 것으로 나타났다. Yeast의 경우 IRA1/2 gene의 손실이나 mammalian ras gene의 transformation으로 인한 heat shock sensitivity가 NF1 gene(2,3) 혹은 GAP(4)의 expression으로 suppression된 것으로 보아 NF1이 GAP protein으로서 ras를 불활성화 시킨다는 것이 판명되었다. 결론적으로 ras의 활성은 GTP bound 혹은 GDP bound의 양쪽형태를 이동하면서 조절되는데 이 기능은 GAP과 GEP 또는 그의 유사 protein들에 의해 수행되며 이러한 regulatory protein들은 growth factor, cytokine 그리고 protein kinase 같은 signal에 의해 활성화된다고 생각된다. 본 총설에서는 ras protein의 여러가지 성질보다는 ras의 modification과 관련하여 항암제로 사용할 수 있는 ras에 specific한 약품개발의 가능성과 현재 알려진 ras의 inhibitor를 중심으로 논하고자 한다.

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The Role of Cell Cycle Regulators in Normal and Malignant Cell Proliferation

  • Lee, Jin-Hwa
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.71-74
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    • 2010
  • Cell proliferation is governed by precise and orderly process the regulation of which involves many different proteins. The key enzyme for cell growth and arrest is cyclin dependent kinases (cdks). In human cells, several cdks orchestrate four distinct cell cycle phases (M, $G_1$, S and $G_2$ ) and they sequentially operate in an order of cdc1, cdk4, cdk6 and cdk2. The regulatory components of cdks consist of cyclins and two family of cdk inhibitors, INK4 (inhibitors of cdk4) and KIP (kinase inhibitor protein). $G_1$ regulatory molecules for cdk mainly respond to environmental cues of mitogenic and anti-mitogenic stimuli and therefore influence activities of $G_1$ cdks, namely, cdk4/6 and cdk2. $G_1$ inhibitors include $p21^{CIP}$ and $p27^{KIP1}$. Between them, $p27^{KIP1}$ has attracted attentions of many researchers because of its characteristic regulatory features and diverse functions. Besides, the role of $p27^{KIP1}$ in cancer development warrants further studies in the future. Therefore, this review will focus on the recent findings and especially on the complexity of regulatory mechanisms of $p27^{KIP1}$.

Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-κB Activity in Triple-Negative Breast Cancer Cells

  • Ma, Chaobing;Zu, Xueyin;Liu, Kangdong;Bode, Ann M.;Dong, Zigang;Liu, Zhenzhen;Kim, Dong Joon
    • Molecules and Cells
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    • v.42 no.9
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    • pp.628-636
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    • 2019
  • Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

Monitoring Seasonal Influenza Epidemics in Korea through Query Search (인터넷 검색어를 활용한 계절적 유행성 독감 발생 감지)

  • Kwon, Chi-Myung;Hwang, Sung-Won;Jung, Jae-Un
    • Journal of the Korea Society for Simulation
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    • v.23 no.4
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    • pp.31-39
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    • 2014
  • Seasonal influenza epidemics cause 3 to 5 millions severe illness and 250,000 to 500,000 deaths worldwide each year. To prepare better controls on severe influenza epidemics, many studies have been proposed to achieve near real-time surveillance of the spread of influenza. Korea CDC publishes clinical data of influenza epidemics on a weekly basis typically with a 1-2-week reporting lag. To provide faster detection of epidemics, recently approaches using unofficial data such as news reports, social media, and search queries are suggested. Collection of such data is cheap in cost and is realized in near real-time. This research aims to develop regression models for early detecting the outbreak of the seasonal influenza epidemics in Korea with keyword query information provided from the Naver (Korean representative portal site) trend services for PC and mobile device. We selected 20 key words likely to have strong correlations with influenza-like illness (ILI) based on literature review and proposed a logistic regression model and a multiple regression model to predict the outbreak of ILI. With respect of model fitness, the multiple regression model shows better results than logistic regression model. Also we find that a mobile-based regression model is better than PC-based regression model in estimating ILI percentages.

Pseudomonas aeruginosa Exotoxin A Induces Apoptosis in Chemoresistant YD-9 Human Oral Squamous Carcinoma Cell Line Via Accumulation of p53 and Activation of Caspases (항암제에 저항성을 가지는 YD-9 human oral squamous carcinoma cell line에서 Pseudomonas aeruginosa exotoxin A의 p53 단백질 누적과 caspase를 활성화 경로를 통해 유도된 세포자멸사)

  • Kim, Gyoo-Cheon;Gil, Young-Gi
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1047-1054
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    • 2009
  • Oral squamous carcinoma (OSC) cells present resistance to chemotherapeutic agents-mediated apoptosis in the late stages of malignancy. Advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers. It was demonstrated here that Pseudomonas aeruginosa exotoxin A (PEA) significantly decreased the viability of chemoresistant YD-9 cells in the apoptosis mechanism. Apoptotic manifestations were evident through changes in nuclear morphology and generation of DNA fragmentation. PEA treatment induced caspase-3, -6 and -9 cleavage, and activation. These events preceded proteolysis of the caspase substrates poly (ADP-ribose) polymerase (PARP), DNA fragmentation factor 45 (DFF45), and lamin A in YD-9 cells. The reduction of mitochondrial membrane potential, release of cytochrome c and SmacjDlABLO from mitochondria to cytosol, andtranslocation of AlF into nucleus were shown. While p53, p21 and $14-3-3{\gamma}$ were upregulated, cyclin Band cdc2 were downregulated by PEA treatment. Taken together, PEA induces apoptosis in chemoresistant YD-9 cells via activation of caspases, mitochondrial events and regulation of cell cycle genes.

The Mechanism of Whole Plant Extract of Viola verecunda on the Proliferation of Dermal Papilla Cells (콩제비꽃 전초 추출물의 모유두세포 증식 기전)

  • Kang, Jung-Il;Seo, Min Jeong;Choi, Youn Kyung;Shin, Su Young;Hwang, Yong;Goh, Jae duk;Yoo, Eun-Sook;Kim, Sang-Cheol;Kang, Hee-Kyoung
    • Korean Journal of Pharmacognosy
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    • v.52 no.1
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    • pp.34-40
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    • 2021
  • Proliferation and maintain of dermal papilla during progression of hair-cycle are crucial to the duration of anagen and regulated by diverse signaling pathway such as PI3K/Akt/Wnt/β-catenin pathway. In this study, we investigated the effects and mechanisms of Viola verecunda on dermal papilla cells. Treatment of dermal papilla cells with whole plant extract of V. verecunda resulted in cell proliferation, which was accompanied by up-regulation of cyclin D1, phospho (ser780)-pRB and cdc2 p34, and down-regulation of p27kip1. V. verecunda extract also promoted the levels of phospho (ser473)-Akt and phospho (ser780)-pRB in a time-dependent manner. Inhibition of PI3K/Akt by Wortmannin suppressed progression of cell-cycle, thereby attenuated the increases in proliferation of dermal papilla cells by V. verecunda extract. We further investigated Wnt/β-catenin pathway with respect to the effects of V. verecunda extract on the proliferation of dermal papilla cells. Treatment with V. verecunda extract results in up-regulation of Wnt/β-catenin proteins such as phospho (ser9)-GSKβ, phospho (ser552)-β-catenin and phospho (ser675)-β-catenin. In addition, Wortmannin abrogated V. verecunda extract mediated up-regulation of cdc2 p34 and down-regulation of p27kip1. These finding reveal that the proliferative effect of V. verecunda mediated by alteration of cell-cycle via activating PI3K/Akt/Wnt pathway in dermal papilla cells.

Molecular Signatures in Chicken Lungs Infected with Avian Influenza Viruses

  • Jeong Woong Park;Marc Ndimukaga;Jaeyoung Heo;Ki-Duk Song
    • Korean Journal of Poultry Science
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    • v.50 no.4
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    • pp.193-202
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    • 2023
  • Influenza IAVs are encapsulated negative-strand RNA viruses that infect many bird species' respiratory systems and can spread to other animals, including humans. This work reanalyzed previous microarray datasets to identify common and specific differentially expressed genes (DEGs) in chickens, as well as their biological activities. There were 760 and 405 DEGs detected in HPAIV and LPAIV-infected chicken cells, respectively. HPAIV and LPAIV have 670 and 315 DEGs, respectively, with both viruses sharing 90 DEGs. Because of HPAIV infection, numerous genes were implicated in a fundamental biological function of the cell cycle, according to the functional annotation of DEGs. Of the targeted genes, expressions of CDC Like Kinase 3 (CLK3), Nucleic Acid Binding Protein 1 (NABP1), Interferon-Inducible Protein 6 (IFI6), PIN2 (TERF1) Interacting Telomerase Inhibitor 1 (PINX1), and Cellular Communication Network Factor 4 (WISP1) were altered in DF-1 cells treated with polyinosinic:polycytidylic acid (PIC), a toll-like receptor 3 (TLR3) ligand, suggesting that transcription of these genes be controlled by TLR3 signaling. To gain a better understanding of the pathophysiology of AIVs in chickens, it is crucial to focus more research on unraveling the mechanisms through which AIV infections may manipulate host responses during the infection process. Insights into these mechanisms could facilitate the development of novel therapeutic strategies.

Effect of a Mixture of Centella asiatica and Rosamarinus officinalis Leaf Extracts on Delayed Cortisol-induced Keratinocyte Migration (병풀과 로즈마리 잎 추출 혼합물의 코티솔로 유도된 각질형성세포 이동지연에 미치는 영향)

  • WonTae Jo;Miji Yeom;ShinHwan Cho;Eunae Cho;Deokhoon Park;Eunsun Jung
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.50 no.2
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    • pp.111-118
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    • 2024
  • A key component of wound healing is epithelialization, which involves the proliferation and migration of epidermal keratinocytes surrounding the wound. Increasing cortisol, a stress hormone, is known to slow the healing process by inhibiting cell proliferation and migration. This study aims to develop an ingredient that can promote delayed wound healing by cortisol through a combination of Centella asiatica (C. asiatica), known for its excellent wound healing effect, and Rosamarinus officinalis (R. officinalis) leaf known for their antipsychotic effect. R. officinalis leaf extract was found to inhibit the activity of 11β-HSD1, an enzyme involved in the production of cortisol. A combination of C. asiatica and R. officinalis leaf extracts (AlfaCalm) was found to enhance cortisol induced delayed keratinocyte migration to a greater extent than C. asiatica extract. AlfaCalm enhanced the expression of CDC42 and the formation of filopodia, which are crucial for the relaxation of the actin skeleton. These results suggest that AlfaCalm can be used as an effective wound healing material in stress condition.

Effects of Salviae miltiorrhizae Radix Extract on Gene Expression of Dendritic cells. (단삼이 수지상 세포의 유전자 발현에 미치는 영향)

  • Chiang, Wen-Lih;Kim, Jong-Han;Choi, Jeong-Hwa;Park, Su-Yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.21 no.3
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    • pp.52-68
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    • 2008
  • Objectives and Methods : Salviae miltiorrhizae Radix (SMR) promotes blood circulation to remove blood stasis, cools the blood to relieve carbuncle, clears away heat from the heart and tranquilizes the mind. This study was designed to investigate the effects of SMR on immuno-potentiative action in terms of changes in the genetic profile of dendritic cells (DC) using by microarray analysis. Results and Conclusion: In this experiment, treatments with more than 250 ${\mu}g/ml$ upto 1000 ${\mu}g/ml$ of SMR elevated the proliferation rates of DC. Microscopic observations confirmed the tendency on proliferation rates. Expression levels of genes related with cellular methabolic process, cell communication, and macromolecule metabolic process were elevated by treatment with SMR in comparison of functional distribution in a Biological Process. In molecular functions, expression levels of genes related with receptor activation, nucleotide binding and nucleic acid binding were elevated. In cellular components, expression levels of genes related to cellular membrane-bound organelles were elevated. In addition, expression levels of genes related to Wnt signalling pathways and the glycerophospholipid metabolism were elevated through analysis using pathway analysis between up-and down-regulated genes in cells treated with SMR. Finally, genes related to JAK2, GRB2, CDC42, SMAD4, B2M, FOS and ESRI located the center of Protein interaction network of genes through treatment with SMR.

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