• Proceedings of the PSK Conference
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• 2003.10b
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• pp.186.3-186.3
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• 2003

The three-dimensional quantitative structure-activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) was performed on indolinones derivatives as an inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR). In the training set, twenty-four indolinone derivatives were aligned based on the indole fragment and the steric and electrostatic fields were included in the analysis. The best predicted model showed the cross-validated coefficient (r$^2$$\sub$cv/) of 0.804 and bib-cross validated coefficient (r$^2$) of 0.942. The CoMFA study can be used to predict several new inhibitors of the FGFR.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1165-1169
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• 2013

To elucidate the role of PKG isoforms in transcriptional control of cyclin D1, we employed a series of expression vectors of PKG $1{\alpha}$ and PKG $1{\beta}$ which encode HA-tagged wild type and constitutively active (SD and ${\Delta}N$) mutants. Our present study demonstrates that both the constitutively active mutants of PKG $1{\beta}$ downregulate the transcription of cyclin D1 when transiently transfected in NIH3T3 cells, whereas PKG $1{\alpha}$ mutants show weak inhibition. We further studied the transcriptional regulators of cyclin D1, such as, c-fos, NF-${\kappa}B$, and CRE by using the luciferase reporter assay. Constitutively active mutants of PKG $1{\beta}$ showed marked transcriptional downregulation of c-fos in NIH3T3 cells, whereas PKG $1{\alpha}$ downregulated c-fos to a lesser extent. We also found that the constitutively active mutants of PKG negatively regulated the activation of NF-${\kappa}B$ and CRE, suggesting their involvement in the regulation of cyclin D1.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.53-53
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• 2003

Calumenin was previously identified as a high affinity Ca$\^$2+/ binding protein in mouse cardiac sarcoplasmic reticulum (SR). For the present study, a 48 kDa skeletal homologue of calumenin was identified by sucrose-density gradient of rabbit skeletal SR membranes, concanavalin A treatment, 2D-gel electrophoresis, $\^$45/Ca$\^$2+/ overlay, Stains-all staining, and MALDI-TOF analysis. We attempted to clone the skeletal calumenin by RT-PCR based on mouse cardiac and human calumenin sequences. The deduced amino acid sequence (315 residues) of the skeletal calumenin showed high identity to mouse cardiac calumenin (90％). As seen in the cardiac calumenin, the deduced sequence contains a 19 amino acid N-terminal signal sequence and a HDEF C-terminal sequence, a putative retrieval signal to ER. Also, the skeletal calumenin contains one N-glycosylation site, three PKC phosphorylation sites, eight casein kinase 2 phosphorylation sites, and 6 EF-hand domains. GST-calumenin showed a conformational change and increased mobility in the presence of Ca$\^$2+/ in SDS-PAGE. Three calumenin interacting proteins (ryanodine receptor 1, glycogen phosphorylase, and phosphofructo kinase) were identified by pull-down assay with GST-calumenin and solubilized SR. All the interactions were Ca$\^$2+/dependent. The present results suggest that calumenin plays an important role in Ca$\^$2+/ homeostasis of muscle cells.

• Journal of Integrative Natural Science
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• v.10 no.3
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• pp.141-147
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• 2017

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in angiogenesis, which is the formation of new blood vessels from pre-existing vessels. Consequently, blocking of the vascular endothelial growth factor receptor (VEGFR-2) by small molecule inhibitors leads to the inhibition of cancer induced angiogenesis. In this study, we performed a two dimensional quantitative structure activity relationship (2D-QSAR) study of 38 N-Phenyl-N'-{4-(4-quinolyloxy) phenyl} urea derivatives as VEGFR-2 inhibitors based on hologram quantitative structure-activity (HQSAR). The model developed showed reasonable $q^2=0.521$ and $r^2=0.932$ values indicating good predictive ability and reliability. The atomic contribution map analysis of most active compound (compound 7) indicates that hydrogen and oxygen atoms in the side chain of ring A and oxygen atom in side chain of ring C contributes positively to the activity of the compounds. The HQSAR model developed and the atomic contribution map can serve as a guideline in designing new compounds for VEGFR-2 inhibition.

• Journal of Life Science
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• v.29 no.1
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• pp.129-134
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• 2019

In a previous study, we isolated 11 different kinds of compounds from ethyl acetate fractions of lees (jubak) which is a by-product of Korean traditional wine production. These compounds were identified as caffeic acid, coumaric acid, D-mannitol, ferulic acid, hesperetin, hesperidin, naringenin, naringin, sinapic acid, syringic acid, and vanilic acid. To evaluate their anti-inflammatory activities in an in vitro model, nitric oxide (NO) production was measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after the treatment of these cells with each compound. Among the various chemicals, hesperetin and naringenin showed the highest inhibition of NO production in the LPS-activated RAW 264.7 cells. Hesperetin was chosen for further study because of its strong anti-inflammatory activity and because the mechanisms underlying its anti-inflammatory properties still remain unclear. Our results showed that hesperetin dramatically inhibited NO production in a dose-dependent manner as compared with in an LPS-only treated group, without affecting cell viability. In addition, hesperetin reduced the protein expression of the pro-inflammatory gene inducible nitric oxide synthase (iNOS) in a dose-dependent manner, whereas it did not affect cyclooxygenase-2 (COX-2) expression. Furthermore, hesperetin inhibited phosphorylation of p38 mitogen- activated protein kinase (MAPK) and extracellular signal regulated kinase (ERK) 1/2, whereas it did not affect phosphorylation of c-jun N- terminal kinase (JNK). The results indicated that hesperetin regulated the LPS-induced inflammatory response by suppressing p38 MAPK and ERK1/2 signaling. Overall, our results may help to understand the mechanisms underlying the anti-inflammatory activity mediated by hesperetin.

• BMB Reports
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• v.43 no.4
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• pp.273-278
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• 2010

The cell cycle is regulated by cyclin-dependent kinase (CDK)-cyclin complexes as well as other regulators. We isolated Kip-related protein 4 (KRP4) cDNA that encodes 289 amino acids including six conserved domains. To investigate the expression pattern of KRP4 as well as of other cell cycle-related genes associated with plant hormones, Arabidopsis seedlings were cultured on MS medium containing auxin or cytokinin. All seedlings treated with phytohormones displayed an increased proportion of cells in S phase. A higher proportion of cells in G2 phase was observed in seedlings treated with NAA. RT-PCR confirmed that the expression of KRP4 was decreased after treatment with phytohormones, and that CDKA and D-type cyclin transcription was increased. Additionally, mitotic cyclins were up-regulated by NAA treatment. These results suggest that KRP4 as well as other cell cycle-related genes might contribute to the control of plant growth in response to exogenous hormones.

• Journal of the Korean Society of Food Culture
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• v.33 no.4
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• pp.337-344
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• 2018

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti-obesity and anti-inflammatory effects. However, the mechanisms underlying these effects in adipocytes are not fully understood. Therefore, this study was conducted to explore the anti-inflammatory mechanisms of GBR on lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes. 3T3-L1 adipocytes were pretreated with GBR extracts (0-20 mg/mL) 1 h before LPS stimulation. The mRNA expression of adipokines and Toll-like receptor 4 (TLR4) were measured by RT-PCR. The protein expressions of TLR4-related molecules were detected by western blotting and nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) activation was measured. Our results showed that GBR extract dose-dependently inhibited mRNA expression of LPS-induced tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). GBR extract was found to inhibit LPS-induced mRNA expression of TLR4 and protein expression of both myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor-activated kinase (ERK) phosphorylation and $NF-{\kappa}B$ activation. These results suggest that GBR extract has the anti-inflammatory effects on LPS-induced inflammation via inhibition of TLR4 signaling, includingthe ERK and $NF-{\kappa}B$ signaling pathways, in adipocytes.

• YAKHAK HOEJI
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• v.46 no.1
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• pp.18-23
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• 2002

Ailanthus altissima has been used to settle an upset stomach, to alleviate a fever and as an insecticide. We reported that the water extract of A. altissima induced apoptotic cell death in Jurkat T-acute Iymphoblastic leukemia cells. Here, we showed the dose-dependent inhibitions of cell viability by the extract, as measured by cell morphology. The cell cycle control genes are considered to play important roles in tumorigenesis. The purpose of the present study is also to investigate the effect of A. altissima on cell cycle progression and its molecular mechanism in the cells. The level of p21 protein was increased after treatment of the extract, whereas both Bcl-2 and Bax protein levels were not changed. These results suggest that A. altissima induces apoptotic cell death via p21-dependent signaling pathway in Jurkat cells which delete wild type p53. Gl checkpoint related gene products tested (cyclin D3, cyclin dependent kinase 4, retinoblastoma, E2Fl) were decreased in their protein levels in a dose-dependent manner after treatment of the extract Taken together, these results indicate that the increase of apoptotic cell death by A. altissima may be due to the inhibition of cell cycle in Jurkat cells.

• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.29-34
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• 2002

Albizzia julibrissin belonging to the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in Oriental traditional medicine. The water extract of A. julibrissin induced apoptosis in Jurkat T-acute lymphoblastic leukemia (ALL) cells as measured by cell morphology. The capability of this herb medicine to induce apoptosis was associated with proteolytic cleavage of specific target protein such as beta-catenin protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of A. julibrissin on cell cycle progression. Our results showed that GI checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.3
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• pp.201-207
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• 2021

The 2019 coronavirus outbreak poses a threat to scientific, societal, financial, and health resources. The complex pathogenesis of severe acute respiratory syndrome coronavirus centers on the unpredictable clinical progression of the disease, which may evolve abruptly and result in critical and life-threatening clinical complications. Effective clinical laboratory biomarkers that can classify patients according to risk are essential for ensuring timely treatment, and an analysis of recently published studies found cytokine storm and coagulation disorders were leading factors of severe COVID-19 complications. The following inflammatory, biochemical, and hematology biomarkers markers have been identified in COVID-19 patients; neutrophil to lymphocyte ratio, c-reactive protein, procalcitonin, urea, liver enzymes, lactate dehydrogenase, serum amyloid A, cytokines, d-dimer, fibrinogen, ferritin, troponin, creatinine kinase, and lymphocyte, leukocyte, and platelet counts. These factors are predictors of disease severity and some are involved in the pathogenesis of COVID-19. CRP is an acute-phase, non-specific serological biomarker of inflammation and infection and is related to disease severities and outcomes. In the present study, CRP levels were found to rise dramatically among COVID-19 patients, and our findings suggest CRP could be utilized clinically to predict COVID-19 prognosis and severity even before disease progression and the manifestation of clinical symptoms.