• Toxicological Research
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• 제15권1호
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• pp.89-93
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• 1999

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) is known to induce cytochrome p450 1A1 and to activate c-Src kinase and p21 Ras. This study examined the molecular interactions of adaptor proteins including Shc, Grb2, and Sos in rat primary hepatocytes and their relationship to the induction of CYP1A1 by TCDD. TCDD induced CYP1A1 level and EROD activity in a dose-dependent mode. Sos/Grb2 association isincreased by TCDDㅑㅜ a dose dependent mode. Tyrosine phosphorylated Shc, mainly p152, onloads to Grb2/Sos complex upon TCDD stimulation. The electrophoretic mobility shift of Sos is showed by TCDD. These results indicate that TCDD modulated the molecular interaction features of adaptor compoes proteins including Shc, Grb2, and Cnl in early signaling pathway of TCDD-mediated CYP 1A1 induction of rat primary hepatocyte.

• 천문학회지
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• 제43권3호
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• pp.95-104
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• 2010

We outline our GRB afterglow observation program using the 1-m telescope at Mt. Lemmon Optical Astronomy Observatory (LOAO), and report the first observations of the GRB afterglows. During the 2007B semester, we performed follow-up imaging obsrevations of 6 GRBs, and succeeded in detecting four GRB afterglows (GRB 071010B, GRB 071018, GRB 071020, and GRB 071025) while placing useful upper limits on the light curves of the other GRBs. Among the observed events, we find that three events are special and interesting. GRB 071010B has a light curve which has an unusually long jet break time of 11.8 days. For GRB 071025, its red R-I(~2) color suggests that it is likely to be at z~5. GRB 071020 has a light curve which shows a clear brightening at 0.3-1 days after the burst, where our LOAO data play a crucial role by providing an unambiguous evidence for the brightening. These are the first successful detections of GRB afterglows by a facility owned and operated by a Korean institution, demonstrating the usefulness of the 1-m telescope for transient phenomena such as GRBs up to very high redshift.

• 생약학회지
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• 제30권4호
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• pp.404-408
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• 1999

SH2 domains and their associated catalytic or noncatalytic proteins constitute critical signal transduction targets for drug discovery. Grb2 associates with phosphotyrosine sites of the activated receptors or Shc via their SH2 domain to link receptor tyrosine kinases to ras signalling. Blocking of the Grb2-Shc complex may be to intervene the oncogenic signal transduction pathways and to develop a new antitumor drug. In the search for blockers of Grb2 SH2-Shc interaction, Lutein, a family of carotenoids, was isolated from the extract of the leaf of Agastache rugosa O. Kuntze as SH2 domain antagonists. The $IC_{50}$ of Lutein against Grb2-Shc binding was $6.8\;{\mu}M$.

• Journal of Ginseng Research
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• 제44권2호
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• pp.258-266
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• 2020

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

• Applied Microscopy
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• 제43권1호
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• pp.27-33
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• 2013

Inflammatory cells express the inflammatory cytokines and growth factors induced by lipopolysaccharide (LPS). Odontoblasts are located at the pulp-dentin interface and extend their cell processes far into the dentin where they are the first cells to encounter microorganisms or their products. Therefore, this study examined the expression of some growth factors related to the signal pathway, such as growth factor receptor binding protein 2 (Grb2)-Ras in odontoblast-like dental pulp cells, after a treatment with LPS. After 60 minutes, the mRNA and protein expression levels of Grb2 and Ras were higher in the LPS-treated cells than in the control cells. The level of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA expression was increased significantly to a level similar to that of Grb2 and Ras at 60 minutes. The platelet-derived growth factor-AA (PDGF-AA) mRNA level was expressed strongly in the odontoblast like dental pulp cells without an association with LPS stimulation. Scanning electron microscopy revealed many extensions of the cytoplasmic processes and the number of processes increased gradually at 30, 60 and 90 minutes after LPS stimulation. From these results VEGF and bFGF expression might be induced through the Grb2-Ras signal transduction pathway in LPS treated odontoblasts.

• 천문학회보
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• 제35권2호
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• pp.35.2-35.2
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• 2010

It is crucial to understand the dust properties in the early universe since they provide important clues about how the early cosmic star formation should be interpreted in the presence of dust extinction. GRB 071025 is an unusually red GRB that occured at high redshift, offering an unique opportunity to study the dust properties in the early universe. We investigate the extinction properties of GRB 071025 through the analysis of RIJHK data obtained with the 1-m telescope at Mt. Lemmon Optical Astronomy Observatory (LOAO) and Simultaneous Quad Infrared Imaging Device (SQIID) on the Kitt-Peak Mayall 4-m telescope. Our dataset is independent from that in a previous work (Perley et al. 2010) where a small systematic photometric errors could complicate the interpretation. After determining the temporal power law exponent with five I-band frames from LOAO, we construct a multi-band monochromatic SED of the GRB afterglow. By using various extinction laws, we find that the SED is best fitted with models that incorporate SNe II dust and derive a photometric redshift of 4.99(+0.12/-0.03). Our results strongly support the prior claim that dusts in GRB 071025 originate mainly from supernovae, implying SNe II predominantly contributed to the dust enrichment in the early universe (z ~ 5).

• 생명과학회지
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• 제17권3호통권83호
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• pp.375-380
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• 2007

Dynamin은 여러 종류의 endocytosis 과정에서 최종적으로 endocytic vesicle을 membrane으로부터 분리하는데 중요한 역할을 하는 단백질이다. 이전의 보고에 의하면 dynamin-2는 Ras에 의해 암화된 세포에서 Ras signal의 신호 전달 단백질인 Grb2의 SH3 domain과 결합한다고 알려져 있다. 하지만 정상적인 세포 (NIH3T3)에 비해 Ras에 의해 암화된 세포 (NIH3T3(Ras))에서 이들 단백질의 발현이 높아지는지에 대해서는 아직 알려진 바가 없다. 본 연구에서는 먼저 NIH3T3 세포와 NIH3T3(Ras) 세포에서 dynamin-2와 Grb2의 단백질 발현을 보았는데, dynamin-2의 경우 NIH3T3 세포에 비해 NIH3T3(Ras) 세포에서 그 발현이 현저히 증가함을 볼 수 있었지만 Grb2의 경우 두 세포에서 발현의 차이를 관찰할 수 없었다. Competitive PCR을 이용하여 mRNA의발현정도를 확인하였을 때, 단백질 발현 정도와 마찬가지로 dynamin-2의 경우 NIH3T3(Ras) 세포에서 약 100배의 증가를 확인하였지만 Grb2의 경우 차이를 볼 수 없었다. Dynamin-2의 promoter 활성을 NIH3T3(Ras) 세포에서 관찰한 결과 start codon으로부터 300 bp에서 200 bp upstream에 dynamin-2의 promoter 활성을 조절하는 부위가 존재함을 확인할 수 있었다.

• BMB Reports
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• 제30권5호
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• pp.303-307
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• 1997

Grb2, which is composed of a Src homology 2 (SH2) domain and two Src homology 3 (SH3) domains, is known to serve as an adaptor protein in signaling for Ras activation. Thus, a blocker of the Grb2 interactions with other proteins can be a potential candidate for an anticancer drug. In this study, we have developed a high throughput screening method for SH3 domain binding ligands and blockers. Firstly, we made and purified the glutathione S-transferase (GST)-fusion proteins with the Grb2 SH2 and SH3 domains, and the entire Grb2. This method measures the binding of a biotin-labeled oligopeptide, derived from a Grb2/SH3 binding motif in the hSos, to the GST-fusion proteins, which are precoated as glutathione S-transferase fusion protein on a solid phase. When $1\;{\mu}g$ of each fusion protein was used to coat the wells, both N- and C- terminal SH3 the domains as well as the whole of Grb2 were able to interact with the biotin-conjugated ligand peptide, while the SH2 domain and GST alone showed no binding affinity. Although N- and C- terminal SH3 domains showed an increase of binding to the ligand peptide in proportion to the amount of peptide, the GST fusion protein with Grb2 demonstrated much higher binding affinity. GST-Grb2 coating on the solid phase showed a saturation curve; 66 and 84% of the maximal binding was observed at 100 and 300 ng/$100\;{\mu}l$, respectively. This binding assay system was peptide sequence-specific, showing a dose-dependent inhibition with the unlabeled peptide of SH3 binding motif. Several other peptides, such as SH2 domain binding motifs and PTB domain binding motif, were ineffective to inhibit the binding to the biotin-conjugated ligand peptide. These results suggest that our method may be useful to screen for new anticancer drug candidates which can block the signaling pathways mediated by SH3 domain binding.

• 천문학회보
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• 제38권2호
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• pp.42.1-42.1
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• 2013

GRB 100205A is a Gamma Ray Burst (GRB) which is suspected to be at $11{\leq}Z{\leq}13.5$ due to its very red H-K color ($(H-K)_{vega}=2.1{\pm}0.5$). We observed a field centered at GRB 100205A with the Wide Field Camera (WFCAM) at the United Kingdom Infrared Telescope (UKIRT) in Hawaii, so as to find a 11 < z < 13 quasar that could be located around the GRB. The images were obtained in J, H, and K filters covering a square area of 0.75 $deg^2$ to the depths of 22.5, 21.4, and 20.2 in Vega magnitude at $5{\sigma}$, respectively. Also using a z-band image observed by MegaCam in Canada France Hawaii Telescope (CFHT), we found 12 candidates that have colors consistent with a quasar at 11 < z < 13 with two criteria; (1) non-detection in z-, J-bands and $(H-K)_{vega}$ > 1.6 (2) only detection in K-band with $(Hlimit-K)_{vega}$ > 1.6. However, we also find 627 red ($(H-K)_{vega}$ > 1.4) objects that are likely to be old or dusty galaxies at $z{\leq}3$, so the 12 candidates could be these red objects. These red objects are found to be strongly clustered in the Ultra Deep Survey (UDS) fields of UKIRT Infrared Deep Sky Survey (UKIDSS) than those in the GRB 100205A field. We suggest a lack of a strongly clustered region surrounding an extremely high-redshift GRB with some limitations.

• Journal of Ginseng Research
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• 제46권4호
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• pp.561-571
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• 2022

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.