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NF-${\kappa}B$ Inhibitor Suppresses Hypoxia-induced Apoptosis of Mouse Pancreatic ${\beta}$-cell Line MIN6

  • Koh, Hyun Sook;Kim, Jae Young
    • Biomedical Science Letters
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    • v.20 no.1
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    • pp.14-24
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    • 2014
  • Hypoxia is one of the main reasons for islet apoptosis after transplantation as well as during isolation. In this study, we attempted to determine the potential usefulness of NF-${\kappa}B$ inhibitor for suppression of hypoxia-induced ${\beta}$-cell apoptosis as well as the relationship between IP-10 induction and ${\beta}$-cell apoptosis in hypoxia. To accomplish this, we cultured the mouse pancreatic ${\beta}$-cell line MIN6 in hypoxia (1% $O_2$). Among several examined chemokines, only IP-10 mRNA expression was induced under hypoxia, and this induced IP-10 expression was due to NF-${\kappa}B$ activity. Since a previous study suggested that IP-10 mediates ${\beta}$-cell apoptosis, we measured hypoxia-induced IP-10 protein and examined the effect of anti-IP-10 neutralizing Ab on hypoxia-induced ${\beta}$-cell apoptosis. However, IP-10 protein was not detected, and anti-IP-10 neutralizing Ab did not rescue hypoxia-induced MIN6 apoptosis, indicating that there is no relationship between hypoxia-induced IP-10 mRNA expression and hypoxia-induced ${\beta}$-cell apoptosis. Since it was still not clear if NF-${\kappa}B$ functions as an apoptotic or anti-apoptotic mediator in hypoxia-induced ${\beta}$-cell apoptosis, we examined possible involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Treatment with 1 ${\mu}M$ NF-${\kappa}B$ inhibitor suppressed hypoxiainduced apoptosis by more than 50%, while 10 ${\mu}M$ AP-1 or 4 ${\mu}M$ NF-AT inhibitor did not, indicating involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Overall, these results suggest that IP-10 is not involved in hypoxia-induced ${\beta}$-cell apoptosis, and that NF-${\kappa}B$ inhibitor can be useful for ameliorating hypoxia-induced ${\beta}$-cell apoptosis.

A Fault Tolerant ATM Switch using a Fully Adaptive Self-routing Algorithm - The Cyclic Banyan Network (실내 무선 통신로에서 파일럿 심볼을 삽입한 Concatenated FEC 부호에 의한 WATM의 성능 개선)

  • 박기식;강영흥;김종원;정해원;양해권;조성준
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.24 no.9A
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    • pp.1276-1284
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    • 1999
  • We have evaluated the BER's and CLP's of Wireless ATM (WATM) cells employing the concatenated FEC code with pilot symbols for fading compensation through the simulation in indoor wireless channel modeled as a Rayleigh and a Rician fading channel, respectively. The results of the performance evaluation are compared with those obtained by employing the convolutional code in the same condition. In Rayleigh fading channel, considering the maximum tolerance BER ( $10^-3$) as a criterion of the voice service, it is blown that the performance improvement of about 4 dB is obtained in terms of $E_b/N_o$ by employing the concatenated FEC code with pilot symbols rather than the convolutional code with pilot symbols.When the values of K parameter which means the ratio of the direct signal to scattered signal power in Rician fading channel are 6 and 10, it is shown that the performance improvement of about 4 dB and 2 dB is obtained, respectively, in terms of $E_b/N_o$ by employing the concatenated FEC code with pilot symbols considering the maximum tolerance BER of the voice service. Also in Rician fading channel of K=6 and K= 10, considering CLP = $10^-3$ as a criterion, it is observed that the performance improvement of about 3.5 dB and1.5 dB is obtained, respectively, in terms of $E_b/N_o$ by employing the concatenated FEC code with pilot symbols.

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Efficient Synthesis of hypho-2,5-$S_2B_7H_{11}$ and Preparation of New nido-, arachno-, and hypho-Metalladithiaborane Clusters Derived from Its Anion hypho-$S_2B_7H_{10}{^-}$

  • 강창환;김성준;고재정;강상욱
    • Bulletin of the Korean Chemical Society
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    • v.16 no.11
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    • pp.1067-1074
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    • 1995
  • Reaction of arachno-S2B7H8- with either THF or 1,2-dimethoxyethane upon refluxing condition results in the formation of the previously known compound hypho-S2B7H10-. Protonation of hypho-S2B7H10- with HCl/Et2O generates hypho-2,5-S2B7H11 in good yield. This hypho-S2B7H10- anion has been employed to generate a series of new nido-, arachno-, and hypho-metalladithiaborane clusters. Reaction of the anion with Cp(CO)2FeCl results in direct metal insertion and the formation of a complex containing the general formula (η5-C5H5)FeS2B7H8. Spectroscopic studies of nido-6-CpFe-7,9-S2B7H8 Ⅰ demonstrated that compound Ⅰ was shown to have an nido-type cage geometry derived from an octadecahedron missing one vertex, with the iron atom occupying the three-coordinate 6-position in the cage and the two sulfurs occupying positions on the open face of the cage. Reaction of hypho-S2B7H10- with CoCl2/Li+[C5H5]- gave the previously known complex arachno-7-CpCo-6,8-S2B6H8 Ⅱ. Also, the reaction of the anion with [Cp*RhCl2]2 gave the complex arachno-7-Cp*Rh-6,8-S2B6H8 Ⅲ, the structure of which was shown to be that of complex Ⅱ. The similarity of the NMR spectra of Ⅱ and Ⅲ suggest that Ⅲ adopts cage structure similar to that previously confirmed for Ⅱ. A series of 9-vertex hypho clusters in which the sulfur atoms are bridged by different species isoelectronic with a BH3 unit, such as HMn(CO)4 or SiR2 have been prepared. Compounds Ⅳ,Ⅴ and Ⅵ are each 2n+4 skeletal electron systems and would be expected according to skeletal electron counting theory to adopt hypho-type polyhedral structures derived from an icosahedron missing three vertices. The complex hypho-1-(CO)4Mn-2,5-S2B6H9 Ⅳ was obtained by the reaction of the anion with (CO)5MnBr and has been shown from spectroscopic data to consist of a (CO)4Mn fragment bound to the two sulfur atoms S2 and S5 of hypho-S2B7H10-. Also, similar hypho-type complexes hypho-1-R2Si-2,5-S2B6H8 (R=CH3 Ⅴ, R=C6H5 Ⅵ) have been prepared from the reaction of hypho-S2B7H10- with R2SiHCl.

Development of Genetic Selection Marker via Examination of Genome in Bacillus velezensis K10 (Bacillus velezensis K10 유전체 분석을 통한 균주 선발 마커 개발)

  • Sam Woong Kim;Young Jin Kim;Tae Wook Lee;Won-Jae Chi;Woo Young Bang;Tae Wan Kim;Kyu Ho Bang;Sang Wan Gal
    • Journal of Life Science
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    • v.33 no.11
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    • pp.897-904
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    • 2023
  • This study was done to develope genetic markers with the unique characteristics of genes according to the genomic information of Bacillus velezensis K10. B. velezensis K10 maintained a total of 4,159,835 bps, which was found to encode 5,136 open reading frames (orfs). B. velezensis K10 was found to have much more gene migration due to external factors overall compared to standard strain B. velezensis JS25R. In order to discover genetic selection markers, orfs on the genome to be easily induced to gene mutation were surveyed such as recombinase, integrase, transposase, and phage-related genes. As a result of the investigation, 9 candidate markers were isolated with high possibility as genetic selection markers. Although a part in the various origin's areas showed specificities in comparison with homology, the selected markers were all existed in phage-related areas because they were relatively lower homologies in phage-related genes. PCR analysis was done on B. licheniformis K12, B. velezensis K10, B. subtilis, and B. cereus to establish them as inter-species candidate selection markers. As a result, it was confirmed that B. velezensis K10-specific PCR products were formed in a total of 6 primer sets such as BV3 and BV5 to 9. On the other hand, analysis at the subspecies level observed the formation of B. velezensis K10-specific PCR products in 4 primer sets such as BV3, 5, 8, and 9. Among them, since BV5 and BV8 were detected by very specific results, we suggest that BV5 and 8 can be used as B. velezensis K10 gene selection markers at the species and sub-species level.

Ginsenoside Rg3 Induces Apoptosis in B16F10 Melanoma Cells (ginsenoside Rg3에 의한 B16F10 흑색종 세포의 세포사멸 유도)

  • Lee, Seul Gi;Kim, Byung Soo;Nam, Ju-Ock
    • Journal of Life Science
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    • v.24 no.9
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    • pp.1001-1005
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    • 2014
  • Ginsenoside Rg3 is one of the active ingredients extracted from red ginseng, and it is an effective chemical component of the human body and well known in herbal medicine as a restorative agent. Several studies have shown that Rg3 has a potent anti-tumor effect on various cancer cell lines. However, Rg3-induced apoptosis in B16F10 melanoma cancer cells is not well understood. In the present study, we tested whether ginsenoside Rg3 could induce apoptosis in B16F10 melanoma cells. We found that Rg3 could inhibit B16F10 melanoma cell viability in a dose-dependent manner, but not normal cells, such as EA.hy.926 and NIH3T3 cells. We also found that Rg3 could induce apoptosis in B16F10 melanoma cells using tunnel-staining assay in a dose-dependent manner. Rg3 treatment induces the phosphorylation of p38 and the expression of Bax, but it inhibits the expressions of the phosphorylation of focal adhesion kinase Bcl2 and pro-caspase3. Taken together, our data suggest that Rg3 could be useful as an anti-cancer agent in B16F10 melanoma cells.

Linarin enhances melanogenesis in B16F10 cells via MAPK and PI3K/AKT signaling pathways

  • Oh, So-Yeon;Kang, Jin Kyu;Hyun, Chang-Gu
    • Journal of Applied Biological Chemistry
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    • v.64 no.4
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    • pp.447-451
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    • 2021
  • In this study, we discovered for the first time that linarin, a flavonoid compound, enhances melanin biosynthesis in B16F10 cells, and subsequently elucidated the underlying mechanism of linarin-induced melanogenesis. Linarin showed no cytotoxicity at a concentration of 42 μM and significantly increased intracellular tyrosinase activity and melanin content in B16F10 cells. Mechanistic analysis showed that linarin increased the expression of tyrosinase, tyrosinase-related protein 1 (TRP-1), and microphthalmia-associated transcription factor (MITF) that are related to melanogenesis. Moreover, linarin decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT). Finally, we evaluated the effect of the structure-activity relationship of linarin and its aglycone on melanogenesis. The results indicated that linarin enhances the expression of melanogenic proteins by activating MITF expression via the modulation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B signaling pathways in B16F10 cells, thereby enhancing melanogenesis.

Trans-10, cis-12 Conjugated Linoleic Acid Modulates Nuclear Factor-${\kappa}B$ p65 Activity on the Production of Tumor Necrosis Factor-${\alpha}$ in Porcine Peripheral Blood Mononuclear Cells (돼지 말초혈액 단핵구세포에서 trans-10, cis-12 conjugated linoleic acid의 TNF-${\alpha}$ 생산에 대한 nuclear factor-${\kappa}B$ p65 활성 조절 효과)

  • Kim, Young-Beum;Lee, Ill-Woo;Kang, Ji-Houn;Yang, Mban-Pyo
    • Journal of Veterinary Clinics
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    • v.28 no.2
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    • pp.190-195
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    • 2011
  • Nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a nuclear transcription factor that modulates the expression of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. trans-10, cis-12 (t10c12)-conjugated linoleic acid (CLA) participates in the inhibition of TNF-${\alpha}$ production upon lipopolysaccharide (LPS)-stimulation. However, in our previous study, t10c12-CLA enhanced the production of TNF-${\alpha}$ by LPS-unstimulated porcine peripheral blood mononuclear cells (PBMCs) and RAW 264.7 macrophages in vitro. To resolve this apparent contradiction, we hypothesized that the effect of t10c12-CLA on TNF-${\alpha}$ production depends on NF-${\kappa}B$ activation induced by LPS stimulation. To test this hypothesis, we assessed the in vitro effect of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ p65 activity in LPS-stimulated and LPS-unstimulated porcine PBMCs. t10c12-CLA treatment resulted in increased TNF-${\alpha}$ production by LPS-unstimulated PBMCs but decreased TNF-${\alpha}$ production by LPS-stimulated PBMCs. t10c12-CLA increased the degradation of inhibitory ${\kappa}B$ ($I{\kappa}B$)-${\alpha}$ protein and activated NF-${\kappa}B$ p65 in LPS-unstimulated PBMCs, but had the opposite effect in LPS-stimulated PBMCs. Notably, t10c12-CLA enhanced NF-${\kappa}B$ p65 binding activity in LPS-unstimulated PBMCs exposed to caffeic acid phenethyl ester (CAPE), a NF-${\kappa}B$ inhibitor. Conversely, it inhibited NF-${\kappa}B$ p65 binding activity in LPS-stimulated PBMCs exposed to CAPE. These results suggest that t10c12-CLA may have different actions under different physiological conditions, and that its effect may be associated with a change in NF-${\kappa}B$ p65 activity.

Antioxidant and Aldo-keto Reductase Family 1 B10 Inhibition Activities of Korean Local Plant Extracts (한국 자생식물 추출물의 항산화 및 Aldo-keto Reductase Family 1 B10 효소 억제 효과)

  • Pan, Cheol-Ho;Lee, Joo-Young;Song, Dae-Geun;Kim, Jong-Hwan;Ahn, Soo-Young;Bae, Deok-Sung;Kim, Young-Hoon;Lee, Jae-Kwon
    • Journal of Applied Biological Chemistry
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    • v.52 no.4
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    • pp.216-220
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    • 2009
  • Aldo-keto reductase family 1 B10 (AKR1B10) has been considered as a potential cancer therapeutic target. Ethanol extracts prepared from 82 Korean local plants were examined for their antioxidant activity and inhibitory effects on recombinant human AKR1B10 (rhAKR1B10) in vitro. 21 extracts showed more than 80% of ABTS radical scavenging activity at $100\;{\mu}g/mL$ and 11 extracts inhibited more than 50% of rhAKR1B10 activity at $10\;{\mu}g/mL$. Especially, 9 extracts showed potent inhibition on rhAKR1B10 activity compared with positive control tetramethylene glutaric acid.

Determination of Li generated from 10B(n·α)7Li reaction in Boric acid solution (붕산수용액에서 10B(n·α)7Li 핵반응에 의해 생성된 Li 정량)

  • Choi, Ke-Chon;Jung, Yongju;Yoon, Jei-Won;Kim, Won-Ho
    • Analytical Science and Technology
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    • v.16 no.6
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    • pp.443-449
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    • 2003
  • Thermal neutron irradiation experiment of boric acid solution was carried out using HANARO in following three conditions: (A) $^{10}B$ concentration = $203.0{\mu}g/mL$, irradiation time = 1 hr; (B) $^{10}B$ concentration = $381.4{\mu}g/mL$, irradiation time = 1 hr; (C) $^{10}B$ concentration = $381.4{\mu}g/mL$, irradiation time = 0.5 hr. The amount of lithium produced from $^{10}B(n{\cdot}{\alpha})^7Li$ reaction which was generated on neutron irradiation, was measured by flameless atomic absorption spectroscopy. The concentration of $^7Li$ measured in the three experiments was $0.18{\mu}g/mL$ (78.3% of theoretical value, $0.23{\mu}g/mL$) in (A), $0.31{\mu}g/mL$ (70.5% of theoretical value, $0.44{\mu}g/mL$) in (B) and $0.16{\mu}g/mL$ (71.6% of theoretical value, $0.22{\mu}g/mL$) in (C). The pH value of irradiated boric acid was shifted to considerably low. It is estimated that boric acid would be transformed into the polyborate fonn, by radiolysis products of water, which has high dissociation constant.

Contractile Response of Methylene Blue on Vascular Smooth Muscles - Rabbit Thoracic Aorta and Porcine Mesenteric Artery - (혈관평활근에 대한 Methylene Blue의 수축작용 - 가토흉부대동맥근과 돼지장간막동맥근 -)

  • Baik, Yung-Hong;Choi, Soo-Yong;Kim, Jae-Ha;Cho, Nam-Kee
    • The Korean Journal of Pharmacology
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    • v.26 no.1
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    • pp.13-23
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    • 1990
  • Methylene Blue (MeB) and gentian violet $(10^{-6}{\sim}10^{-4}\;M)$ produced contractions in isolated thoracic aortic preparations of rabbits in a dose-dependent fashion, while other dyes, evans blue and eosine yellowish, did not affect the basal tension in the same range of doses. Porcine mesenteric arterial rings also responded to MeB with dose-dependent contractions. Single dose of $10^{-4}$ M MeB produced a biphasic response: contraction followed by relaxation. The contraction developed slowly within $2{\sim}4$ min and peaked in about 20 minutes and then slowly relaxed to the basal level. Tyramine $(10^{-4}\;M)$ also induced contraction but it developed faster and was more persistent than that of MeB. While the tyramine-induced tension was reproducible, the MeB-induced one wat not reiterable until 3 to 5 hours after washing out the MeB. Adding $10^{-4}$ M MeB further potentiated the contraction induced by $10^{-4}$ M tyramine. However, the MeB contraction was not affected by further addition or tyramine. Both tyramine- and MeB-induced tensions were abolished or significantly inhibited by pretreatment with various drugs acting on the sympathetic nervous system. The tyramine-induced tension was more sensitive to guanethidine and 6-hydroxydopamine than the MeB-induced tension, while the latter was more sensitive to $Ca^{2+}-free$ PSS and reserpine. But they have similar sensitivity to prazosin. The MeB-induced tension was significantly inhibited but not abolished by 6-hydroxydopamine pretreatment. However, either tyramine or 6-hydroxydopamine could not affect the basal tension of the ring that MeB once had been tested. These results suggest that MeB-induced contractions of rabbit thoracic aorta and porcine mesenteric artery result from a release of endogenous norepinephrine from adrenergic nerve endings and are dependent in part on extracellular calcium, and that the potency of MeB to release or to deplete norepinephrine is greater than that of either tyramine or 6-hydroxydopamine.

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