• Title/Summary/Keyword: molecular map

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Molecular Mechanism of NO-induced Cell Death of PC12 Cells by $IFN{\gamma}\;and\;TNF{\alpha}$

  • Yi, Seh-Yoon;Han, Seon-Kyu;Lee, Jee-Yeon;Yoo, Young-Sook
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.196-202
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    • 2005
  • Nitric oxide (NO) is a small, diffusible, and highly reactive molecule, which plays dichotomous regulatory roles under physiological and pathological conditions. NO promotes apoptosis in some cells, and inhibits apoptosis in other cells. In the present study, we attempted to characterize the NO signaling pathway and cellular response in PC12 cells treated with cytokines. $IFN{\gamma}\;and\;TNF{\alpha}$ treatment resulted in a synergistic increase of nitrite accumulation, with the induction of inducible nitric oxide synthase (iNOS) in the PC12 cells. Moreover, as nitrite concentration increased, cell viability decreased. In order to explore MAP kinase involvement in nitric oxide production resultant from $IFN{\gamma}\;and\;TNF{\alpha}$ stimulation, we measured the activation of MAP kinase using specific MAP kinase inhibitors. PC12 cells pretreated with SB203580, a p38 MAP kinase-specific inhibitor, resulted in the inhibition of iNOS expression and NO production. However, PD98059, an ERK/MAP kinase-specific inhibitor, was not observed to exert such an effect. In addition, Stat1 activated by $IFN{\gamma}\;and\;TNF{\alpha}$ was interacted with p38 MAPK. These data suggest that p38 MAP kinase mediates cytokine-mediated iNOS expression in the PC12 cells, and Jak/Stat pathway interferes with p38 MAPK signaling pathway.

Analysis of Dual Phosphorylation of Hog1 MAP Kinase in Saccharomyces cerevisiae Using Quantitative Mass Spectrometry

  • Choi, Min-Yeon;Kang, Gum-Yong;Hur, Jae-Young;Jung, Jin Woo;Kim, Kwang Pyo;Park, Sang-Hyun
    • Molecules and Cells
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    • v.26 no.2
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    • pp.200-205
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    • 2008
  • The mitogen-activated protein kinase (MAPK) signaling pathway is activated in response to extracellular stimuli and regulates various activities in eukaryotic cells. Following exposure to stimuli, MAPK is known to be activated via dual phosphorylation at a conserved TxY motif in the activation loop; both threonine and tyrosine residues are phosphorylated by an upstream kinase. However, the mechanism underlying dual phosphorylation is not clearly understood. In the budding yeast Saccharomyces cerevisiae, the Hog1 MAPK mediates the high-osmolarity glycerol (HOG) signaling pathway. Tandem mass spectrometry and phosphospecific immunoblotting were performed to quantitatively monitor the dynamic changes occurring in the phosphorylation status of the TxY motif of Hog1 on exposure to osmotic stress. The results of our study suggest that the tyrosine residue is preferentially and dynamically phosphorylated following stimulation, and this in turn leads to the dual phosphorylation. The tyrosine residue was hyperphosphorylated in the absence of a threonine residue; this result suggests that the threonine residue is critical for the control of signaling noise and adaptation to osmotic stress.

The distribution of the molecular hydrogen in the Milky way

  • Jo, Young-Soo;Seon, Kwang-Il;Min, Kyoung-wook
    • The Bulletin of The Korean Astronomical Society
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    • v.41 no.2
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    • pp.40.1-40.1
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    • 2016
  • We present the far-ultraviolet fluorescent molecular hydrogen ($H_2$) emission map observed with FIMS/SPEAR for ~76% of the sky. The fluorescent $H_2$ emission is found to be saturated by strong dust extinction at the optically thick, Galactic plane region. However, the extinction-corrected intensity of fluorescent $H_2$ emission is found to have strong linear correlations with the well-known tracers of the cold interstellar medium, such as the E(B-V) color excess, neutral hydrogen column density N(HI), $H{\alpha}$ emission, and CO $J=1{\rightarrow}0$ emission. The all-sky molecular hydrogen column density map is also obtained using a photodissociation region model. We also derive the gas-to-dust ratio, hydrogen molecular fraction ($f_{H2}$), and $CO-to-H_2$ conversion factor ($X_{CO}$) of the diffuse interstellar medium. The gas-to-dust ratio is consistent with the standard value $5.8{\times}10^{21}atoms\;cm^{-2}mag^{-1}$, and the $X_{CO}$ tends to increase with E(B-V), but converges to the Galactic mean value $1.8{\times}10^{20}cm^{-2}K^{-1}km^{-1}s$ at optically thick regions with E(B-V)>2.0.

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Binding Models of Flavonols to Human Vascular Endothelial Growth Factor Receptor 2

  • Lee, Jee-Young;Jeong, Ki-Woong;Kim, Woong-Hee;Heo, Yong-Seok;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.30 no.9
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    • pp.2083-2086
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    • 2009
  • Human vascular endothelial growth factor receptor 2 (hVEGFR2) is an important signaling protein involved in angiogenesis and attractive drug target in cancer therapy. It has been reported that flavonols, a class of flavonoids, have anti-angiogenic activity in various cancer cell lines. We performed receptor-oriented pharmacophore based in silico screening for identification of hVEGFR2 inhibitors from flavonol database. By comparing with three X-ray complex structures of hVEGFR2 and its inhibitors, we evaluated the specific interactions between inhibitors and receptors and determined a single pharmacophore map. This map consisted of four features, a hydrogen bonding acceptor (HBA) on Cys917, two hydrogen bonding donors on Glu917 (HBD1) and Glu883 (HBD2), and one hydrophobic interaction (Lipo) with Val846, Ala864, Val897, Val914 and Phe1045 of hVEGFR2. Using this map, we searched a flavonol database including 9 typical flavonols and proposed that five flavonols, kaempferol, quercetin, fisetin, morin, and rhamnetin can be potent inhibitors of hVEGFR2. 3-OH of C-ring and 4’-OH of B-ring of flavonols are the essential features for hVEGFR2 inhibition. This study will be helpful for understanding the mechanism of inhibition of hVEGFR2 by natural products.

Genome Research on Peach and Pear

  • Hayashi, Tateki;Yamamoto, Toshiya
    • Journal of Plant Biotechnology
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    • v.4 no.2
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    • pp.45-52
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    • 2002
  • A lot of SSRs (simple sequence repeats) in peach and pear from enriched genomic libraries and in peach from a cDNA library were developed. These SSRs were applied to other related species, giving phenograms of 52 Prunes and 60 pear accessions. Apple SSRs could also be successfully used in Pyrus spp. Thirteen morphological traits were characterized on the basis of the linkage map obtained from an $F_2$ population of peach. This map was compiled with those morphological markers and 83 DNA markers, including SSR markers used as anchor loci, to compare different peach maps. Molecular markers tightly linked to new root-knot nematode resistance genes were also found. A linkage map including disease related genes, pear scab resistance and black spot susceptibility, in the Japanese pear Kinchaku were constructed using 118 RAPD markers. Another linkage map, of the European pear Bartlett, was also constructed with 226 markers, including 49 SSRs from pear, apple, peach and cherry. Maps of other Japanese pear cultivars, i.e., Kousui and Housui, were also constructed. These maps were the first results of pear species.

Transient activation of the MAP kinase signaling pathway by the forward signaling of EphA4 in PC12 cells

  • Shin, Jong-Dae;Gu, Chang-Kyu;Kim, Ji-Eun;Park, Soo-Chul
    • BMB Reports
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    • v.41 no.6
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    • pp.479-484
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    • 2008
  • In the present study, we demonstrate that ephrin-A5 is able to induce a transient increase of MAP kinase activity in PC12 cells. However, the effects of ephrin-A5 on the MAP kinase signaling pathway are about three-fold less than that of EGF. In addition, we demonstrate that EphA4 is the only Eph member expressed in PC12 cells, and that tyrosine phosphorylation induced by ephrin-A5 treatment is consistent with the magnitude and longevity of MAP kinase activation. Experiments using the Ras dominant negative mutant N17Ras reveal that Ras plays a pivotal role in ephrin-A5-induced MAP kinase activation in PC12 cells. Importantly, we found that the EphA4 receptor is rapidly internalized by endocytosis upon engagement of ephrin-A5, leading to a subsequent reduction in the MAP kinase activation. Together, these data suggest a novel regulatory mechanism of differential Ras-MAP kinase signaling kineticsexhibited by the forward signaling of EphA4 in PC12 cells.

Quantitative Assessment Technology of Small Animal Myocardial Infarction PET Image Using Gaussian Mixture Model (다중가우시안혼합모델을 이용한 소동물 심근경색 PET 영상의 정량적 평가 기술)

  • Woo, Sang-Keun;Lee, Yong-Jin;Lee, Won-Ho;Kim, Min-Hwan;Park, Ji-Ae;Kim, Jin-Su;Kim, Jong-Guk;Kang, Joo-Hyun;Ji, Young-Hoon;Choi, Chang-Woon;Lim, Sang-Moo;Kim, Kyeong-Min
    • Progress in Medical Physics
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    • v.22 no.1
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    • pp.42-51
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    • 2011
  • Nuclear medicine images (SPECT, PET) were widely used tool for assessment of myocardial viability and perfusion. However it had difficult to define accurate myocardial infarct region. The purpose of this study was to investigate methodological approach for automatic measurement of rat myocardial infarct size using polar map with adaptive threshold. Rat myocardial infarction model was induced by ligation of the left circumflex artery. PET images were obtained after intravenous injection of 37 MBq $^{18}F$-FDG. After 60 min uptake, each animal was scanned for 20 min with ECG gating. PET data were reconstructed using ordered subset expectation maximization (OSEM) 2D. To automatically make the myocardial contour and generate polar map, we used QGS software (Cedars-Sinai Medical Center). The reference infarct size was defined by infarction area percentage of the total left myocardium using TTC staining. We used three threshold methods (predefined threshold, Otsu and Multi Gaussian mixture model; MGMM). Predefined threshold method was commonly used in other studies. We applied threshold value form 10% to 90% in step of 10%. Otsu algorithm calculated threshold with the maximum between class variance. MGMM method estimated the distribution of image intensity using multiple Gaussian mixture models (MGMM2, ${\cdots}$ MGMM5) and calculated adaptive threshold. The infarct size in polar map was calculated as the percentage of lower threshold area in polar map from the total polar map area. The measured infarct size using different threshold methods was evaluated by comparison with reference infarct size. The mean difference between with polar map defect size by predefined thresholds (20%, 30%, and 40%) and reference infarct size were $7.04{\pm}3.44%$, $3.87{\pm}2.09%$ and $2.15{\pm}2.07%$, respectively. Otsu verse reference infarct size was $3.56{\pm}4.16%$. MGMM methods verse reference infarct size was $2.29{\pm}1.94%$. The predefined threshold (30%) showed the smallest mean difference with reference infarct size. However, MGMM was more accurate than predefined threshold in under 10% reference infarct size case (MGMM: 0.006%, predefined threshold: 0.59%). In this study, we was to evaluate myocardial infarct size in polar map using multiple Gaussian mixture model. MGMM method was provide adaptive threshold in each subject and will be a useful for automatic measurement of infarct size.

Genetic Analysis of Flower Color Traits in Calanthe discolor, C. sieboldii, and Variants Using Molecular Linkage Map (연관지도를 이용한 새우난초, 금새우난초, 변이종의 화색의 유전분석)

  • Cho, Dong-Hoon;Chung, Mi-Young;Jee, Sun-Ok;Kim, Chang-Kil;Chung, Jae-Dong;Kim, Kyung-Min
    • Journal of Life Science
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    • v.19 no.9
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    • pp.1239-1244
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    • 2009
  • This study was conducted to clarify the genetic relationship between Calanthe discolor, C. sieboldii and variants, and the cause of flower color variations by using a molecular linkage map and a quantitative trait loci (QTL) analysis for flower and lip color in Calanthe species native to Korea. Twenty plants were included in three C. discolor and three C. sieboldii, and fourteen variants were obtained from their habitat, Jeju-do in Korea. The flowers of C. discolor were brownish red, the values of Commission Internationale de I'Eclairage (CIE) Lab were between 40 and 50. The flowers of C. sieboldii were yellowish, the values of CIE Lab were between 110 and 130. The variants had various mixed colors that were thought to have originated from natural hybridization between C. discolor and C. sieboldii, and the values of CIE Lab were between 50 and 70. The colors of the lips were usually divided into white and yellow. C. discolor had a white lip, C. sieboldii had a yellow one, and the variants had a white to yellow one. The CIE Lab value of each color was 90 in white and 110 to 120 in yellow lips. A molecular linkage mapping was constructed based on the segregation of 154 RAPD markers using a MAPL program. Sixteen linkage groups containing 66 markers were established. It covered a total map distance of 220.4 cM. The distance between adjacent markers ranged from 0 to 6.6 cM, with an average distance of 3.3 cM. These markers are thought to be closely associated with flower and lip color expression. Among the 16 molecular linkage groups, 3 QTLs had flower color trait loci and 1 QTL had lip color trait loci.