• Molecules and Cells
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• v.20 no.2
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• pp.280-287
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• 2005

The insulin-mediated Ras/mitogen-activated protein (MAP) kinase cascade was examined in SK-N-BE(2) and PC12 cells, which can and cannot produce reactive oxygen species (ROS), respectively. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) was much lower in SK-N-BE(2) cells than in PC12 cells when the cells were treated with insulin. The insulin-mediated interaction of IRS-1 with Grb2 was observed in PC12 but not in SK-N-BE(2) cells. Moreover, the activity of extracellular-signal-related kinase (ERK) was much lower in SK-N-BE(2) than in PC12 cells when the cells were treated with insulin. Application of exogenous $H_2O_2$ caused increased tyrosine phosphorylation and Grb2 binding to IRS-1 in SK-N-BE(2) cells, while exposure to an $H_2O_2$ scavenger (N-acetylcysteine) or to a phophatidylinositol-3 kinase inhibitor (wortmannin), and expression of a dominant negative Rac1, decreased the activation of ERK in insulin-stimulated PC12 cells. These results indicate that the transient increase of ROS is needed to activate ERK in insulin-mediated signaling and that an inability to generate ROS is the reason for the insulin insensitivity of SK-N-BE(2) cells.

• Journal of Microbiology and Biotechnology
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• v.10 no.4
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• pp.544-546
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• 2000

Grb2 is an important adaptor protein in the mitogenic Ras signaling pathway of receptor tyrosine kinases, and contains one SH2 domain and two SH3 domains. The SH2 domain binds to specific phosphotyrosine motifs on receptors or adaptor proteins such as Shc. The SH2 domain antagonists may lead to blocking of the oncogenic Ras signals and to developing new antitumor agents. In the course of screening SH2 antagonists from natural sources, cslerotiorin (1) and isochromophilone IV (2) were isolated from a strain, Penicillium multicolor F1753, and their structures were established by NMR spectral data. The metabolites significantly inhibited the binding between the Grb2-SH2 domain and phosphopeptide derived from the Shc protein, with $IC_{50}$ values of $22{\;}\mu\textrm{M}{\;}and{\;}48{\;}\mu\textrm{M}$ for (1) and (2), respectively. The compounds are the first nonpeptidic inhibitors of the SH2 domain from a natural source.

• The Bulletin of The Korean Astronomical Society
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• v.32 no.2
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• pp.44.2-44.2
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• 2007

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1707-1714
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• 2012

Grb2 is an adapter protein involved in the signal transduction and cell communication. The Grb2 is responsible for initiation of kinase signaling by Ras activation which leads to the modification in transcription. Ligand based pharmacophore approach was applied to built the suitable pharmacophore model for Grb2. The best pharmacophore model was selected based on the statistical values and then validated by Fischer's randomization method and test set. Hypo1 was selected as a best pharmacophore model based on its statistical values like high cost difference (182.22), lowest RMSD (1.273), and total cost (80.68). It contains four chemical features, one hydrogen bond acceptor (HBA), two hydrophobic (HY), and one ring aromatic (RA). Fischer's randomization results also shows that Hypo1 have a 95% significant level. The correlation coefficient of test set was 0.97 which was close to the training set value (0.94). Thus Hypo1 was used for virtual screening to find the potent inhibitors from various chemical databases. The screened compounds were filtered by Lipinski's rule of five, ADMET and subjected to molecular docking studies. Totally, 11 compounds were selected as a best potent leads from docking studies based on the consensus scoring function and critical interactions with the amino acids in Grb2 active site.

• The Bulletin of The Korean Astronomical Society
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• v.24 no.2
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• pp.111-112
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• 1999

• Applied Biological Chemistry
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• v.41 no.2
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• pp.197-200
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• 1998

The MeOH extracts obtained from the flower petals of Carthamus tinctorius were solvent-fractionated with EtOAc, n-BuOH, and $H_2O$, successively. From the n-BuOH extract 2 flavonoid compounds were isolated through the repeated silica gel column chromatographies. From not only the results of physico-chemical data including HMBC but also the adaptation of acid hydrolysis, the chemical structures of the compounds were determined as $3-O-[{\beta}-D-glucopyranosyl(1{\rightarrow}2)\;{\beta}-D-glucopyranosyl]\;kaempferol$ and $3-O-[{\alpha}-L-rhamnopyranosyl(1{\rightarrow}6)\;{\beta}-D-glucopyranosyl]\;kaempferol$. The compounds exhibited $IC_{50}$ values in Grab2-Shc activity to be 43 and $47{\mu}g/ml$, respectively.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.3
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• pp.635-648
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• 1998

The clinical use of fluoride with a well known osteogenic action in osteoporotic patients is rational, because this condition is characterized by impaired bone formation. However, its anabolic effect has not been demonstrated well in vitro. The purpose of this study was to investigate the effects of sodium fluoride on the physiological role of osteoblastic cell. Osteoblastic cells were isolated from fetal rat calvaria. The results were as follows : 1. Mineralized nodules were shown in osteoblastic cell cultures, which had been maintained in the presence of ascorbic acid and ${\beta}-glycerophosphate$ up to 21 days. When cultures were treated with pulses of 48 hr duration before apparent mineralization was occurring, 2-fold increased in their number was detected. 2. Alkaline phosphatase activity of osteoblastic cells was inhibited by sodium fluoride in dose dependent manner. 3. The effect of sodium fluoride on the osteoblastic cell proliferation was measured by the incorporation of $[^3H]$-thymidine into DNA. As a result, sodium fluoride at $1{\sim}100{\mu}M$ increased the $[^3H]$-thymidine incorporation into DNA in a dose dependent manner. 4. The signaling mechanism activated by sodium fluoride dose-dependently enhanced the tyrosine phosphorylation of the adaptor molecule $Shc^{p66}$ and their association with Grb2, one of earlier events in a MAP kinase activation pathway cascade used by a significant subset of G protein-coupled receptors. 5. The phosphorylation of CREB(cAMP response element binding protein)was inhibited by the sodium fluoride in MC3T3E1 cells. In conclusion, the results of this study suggested that the mitogenic effect of the sodium fluoride in MC3T3E1 cell was stimulated in a dose-dependent manner and suggested "an important role for the interaction between She and Grb2" in controlling the proliferation of osteoblasts.

• The Bulletin of The Korean Astronomical Society
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• v.40 no.1
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• pp.49.3-50
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• 2015

Synchrotron radiation of relativistic electrons is an important radiation mechanism in many astrophysical sources. In the sources where the synchrotron cooling timescale is shorter than the dynamical timescale, electrons are cooled down below the minimum injection energy. It has been believed that such fast-cooling electrons have a power-law distribution in energy with an index -2, and their synchrotron radiation has a photon spectral index -1.5. On the other hand, in a transient expanding astrophysical source, such as a gamma-ray burst (GRB), the magnetic field strength in the emission region continuously decreases with radius. Here we study such a system, and find that in a certain parameter regime, the fast-cooling electrons can have a harder energy spectrum. We apply this new physical regime to GRBs, and suggest that the GRB prompt emission spectra whose low-energy photon spectral index has a typical value -1 could be due to synchrotron radiation in this moderately fast-cooling regime.

• The Bulletin of The Korean Astronomical Society
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• v.37 no.1
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• pp.32.2-32.2
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• 2012

Gamma Ray Bursts (GRBs) are the most energetic events in the universe, and are known to arise from the death of massive stars in many cases. Their extreme brightness makes it possible to detect them at very high redshift (z > 6.5), well into the epoch of re-ionization, providing us with an opportunity to investigate the deaths of the first stars when the universe was much younger than 1 Gyr. Here, we report the discovery of GRB 100905A, a GRB at $z$ - 7.5 (age of the universe at 700 Myr). Our observation revealed a strong spectral break between z and J band, allowing us to estimate its photometric redshift. Its gamma-ray light curve shows a very short duration of about 0.7 sec, the shortest duration event at z > 5. Investigation of this and three other known GRBs at z > 6.5 reveals that they are all short duration bursts. This is puzzling, considering that GRBs from death of massive stars do not show short duration. We suggest two possible explanations for this: (i) the BAT light curves of the high redshift GRBs suffered from observational selection effect where we are only observing the very tip of the light curve; (ii) the stars in the early universe had a peculiar nature that are different from ordinary stars at lower redshifts.

• The Bulletin of The Korean Astronomical Society
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• v.35 no.1
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• pp.64.2-64.2
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• 2010

From 2009, CEOU of Seoul National University has been utilizing the United Kingdom Infrared Telescope (UKIRT) at Mauna Kea, Hawaii, as one of its research facilities. UKIRT is a telescope with 3.8m primary mirror, and it is currently the largest telescope specialized for infrared observations. We will summarize our research activities using UKIRT, which include Infrared Medium-deep Survey (IMS) of proto-clusters and high redshift quasars, NIR imaging programs of Gamma Ray Bursts (GRBs), Gamma Ray sources, and SNUQSO quasars. Our research programs include international collaboration with the UK GRB team, the NASA/Swift team, Pomona College, and National Central University of Taiwan. We will also touch on our future plan of using UKIRT.