• Title/Summary/Keyword: 표적신호

Search Result 554, Processing Time 0.028 seconds

Microarray Analysis of Gene Expression in Rat Glioma after Ethanol Treatment (에탄올 처리에 의한 흰쥐 신경아교종(Glioma) 세포에서의 유전자 발현 - DNA 칩을 이용한 분석 -)

  • Lee, So Hee;Oh, Dong-Yul;Han, Jin-Hee;Choi, Ihn-Geun;Jeon, Yang-Whan;Lee, Joon-Noh;Lee, Tae Kyung;Jeong, Jong-Hyun;Jung, Kyung Hwa;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
    • /
    • v.14 no.2
    • /
    • pp.115-121
    • /
    • 2007
  • Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

  • PDF

Pathophysiological Regulation of Vascular Smooth Muscle Cells by Prostaglandin F2α-dependent Activation of Phospholipase C-β3 (Prostaglandin F2α 의존적 phospholipase C-β3 활성화에 의한 혈관평활근세포의 병태생리 조절 연구)

  • Kang, Ki Ung;Oh, Jun Young;Lee, Yun Ha;Lee, Hye Sun;Jin, Seo Yeon;Bae, Sun Sik
    • Journal of Life Science
    • /
    • v.28 no.12
    • /
    • pp.1516-1522
    • /
    • 2018
  • Atherosclerosis is an obstructive vessel disease mainly caused by chronic arterial inflammation to which the proliferation and migration of vascular smooth muscle cells (VSMCs) is the main pathological response. In the present study, the primary responsible inflammatory cytokine and its signaling pathway was investigated. The proliferation and migration of VSMCs was significantly enhanced by the prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$), while neither was affected by tumor necrosis factor ${\alpha}$. Prostacyclin $I_2$ was seen to enhance the proliferation of VSMCs while simultaneously suppressing their migration. Both prostaglandin $D_2$ and prostaglandin $E_2$ significantly enhanced the migration of VSMCs, however, proliferation was not affected by either of them. The proliferation and migration of VSMCs stimulated by $PGF_{2{\alpha}}$ progressed in a dose-dependent manner; the $EC_{50}$ value of both proliferation and migration was $0.1{\mu}M$. VSMCs highly expressed the phospholipase isoform $C-{\beta}3$ ($PLC-{\beta}3$) while others such as $PLC-{\beta}1$, $PLC-{\beta}2$, and $PLC-{\beta}4$ were not expressed. Inhibition of the PLCs by U73122 completely blocked the $PGF_{2{\alpha}}$-induced migration of VSMCs, and, in addition, silencing $PLC-{\beta}3$ significantly diminished the $PGF_{2{\alpha}}$-induced proliferation and migration of VSMCs. Given these results, we suggest that $PGF_{2{\alpha}}$ plays a crucial role in the proliferation and migration of VSMCs, and activation of $PLC-{\beta}3$ could be involved in their $PGF_{2{\alpha}}$-dependent migration.

The Lung Expression of Proinflammatory Cytokines, TNF-$\alpha$ and Interleukin 6, in Early Periods of Endotoxemia (내독소혈증 유발 급성폐손상에서 폐장내 Proinflammatory Cytokines 발현에 관한 고찰)

  • Moon, Seung-Hyug;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Shin-Je
    • Tuberculosis and Respiratory Diseases
    • /
    • v.45 no.3
    • /
    • pp.553-564
    • /
    • 1998
  • Background: The immediate hoot response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is further amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-$\alpha$, IL 6 in early periods of endotoxin induced acute lung injury (ALI). Method: The healthy male Sprague-Dawley, weighted 150 - 250g, were divided into saline control (NC) and endotoxemia-induced ALI (ETX-), and leukopenic endotoxemia-induced ALI (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-$\alpha$ and IL 6 by a bioassy using MIT method. We also examined the localization of TNF-$\alpha$ and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). Results: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC(p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC. but PMN count was markedly reduced and it took part in less than 0.1 % of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group Compared to NC (p<0.05), but there was significant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential The concentration of TNF-$\alpha$ and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-$\alpha$- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macrophages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. Conclusion: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs's certain inflammatory role, particularly in endotoxemia-induced acute lung injury.

  • PDF

Evaluation of the Usefulness of Restricted Respiratory Period at the Time of Radiotherapy for Non-Small Cell Lung Cancer Patient (비소세포성 폐암 환자의 방사선 치료 시 제한 호흡 주기의 유용성 평가)

  • Park, So-Yeon;Ahn, Jong-Ho;Suh, Jung-Min;Kim, Yung-Il;Kim, Jin-Man;Choi, Byung-Ki;Pyo, Hong-Ryul;Song, Ki-Won
    • The Journal of Korean Society for Radiation Therapy
    • /
    • v.24 no.2
    • /
    • pp.123-135
    • /
    • 2012
  • Purpose: It is essential to minimize the movement of tumor due to respiratory movement at the time of respiration controlled radiotherapy of non-small cell lung cancer patient. Accordingly, this Study aims to evaluate the usefulness of restricted respiratory period by comparing and analyzing the treatment plans that apply free and restricted respiration period respectively. Materials and Methods: After having conducted training on 9 non-small cell lung cancer patients (tumor n=10) from April to December 2011 by using 'signal monitored-breathing (guided- breathing)' method for the 'free respiratory period' measured on the basis of the regular respiratory period of the patents and 'restricted respiratory period' that was intentionally reduced, total of 10 CT images for each of the respiration phases were acquired by carrying out 4D CT for treatment planning purpose by using RPM and 4-dimensional computed tomography simulator. Visual gross tumor volume (GTV) and internal target volume (ITV) that each of the observer 1 and observer 2 has set were measured and compared on the CT image of each respiratory interval. Moreover, the amplitude of movement of tumor was measured by measuring the center of mass (COM) at the phase of 0% which is the end-inspiration (EI) and at the phase of 50% which is the end-exhalation (EE). In addition, both observers established treatment plan that applied the 2 respiratory periods, and mean dose to normal lung (MDTNL) was compared and analyzed through dose-volume histogram (DVH). Moreover, normal tissue complication probability (NTCP) of the normal lung volume was compared by using dose-volume histogram analysis program (DVH analyzer v.1) and statistical analysis was performed in order to carry out quantitative evaluation of the measured data. Results: As the result of the analysis of the treatment plan that applied the 'restricted respiratory period' of the observer 1 and observer 2, there was reduction rate of 38.75% in the 3-dimensional direction movement of the tumor in comparison to the 'free respiratory period' in the case of the observer 1, while there reduction rate was 41.10% in the case of the observer 2. The results of measurement and comparison of the volumes, GTV and ITV, there was reduction rate of $14.96{\pm}9.44%$ for observer 1 and $19.86{\pm}10.62%$ for observer 2 in the case of GTV, while there was reduction rate of $8.91{\pm}5.91%$ for observer 1 and $15.52{\pm}9.01%$ for observer 2 in the case of ITV. The results of analysis and comparison of MDTNL and NTCP illustrated the reduction rate of MDTNL $3.98{\pm}5.62%$ for observer 1 and $7.62{\pm}10.29%$ for observer 2 in the case of MDTNL, while there was reduction rate of $21.70{\pm}28.27%$ for observer 1 and $37.83{\pm}49.93%$ for observer 2 in the case of NTCP. In addition, the results of analysis of correlation between the resultant values of the 2 observers, while there was significant difference between the observers for the 'free respiratory period', there was no significantly different reduction rates between the observers for 'restricted respiratory period. Conclusion: It was possible to verify the usefulness and appropriateness of 'restricted respiratory period' at the time of respiration controlled radiotherapy on non-small cell lung cancer patient as the treatment plan that applied 'restricted respiratory period' illustrated relative reduction in the evaluation factors in comparison to the 'free respiratory period.

  • PDF