• 제목/요약/키워드: AG490

검색결과 26건 처리시간 0.027초

AG490, a Jak2-specific Inhibitor, Induces Osteoclast Survival by Activating the Akt and ERK Signaling Pathways

  • Kwak, Han Bok;Sun, Hyun Min;Ha, Hyunil;Lee, Jong Ho;Kim, Ha Neui;Lee, Zang Hee
    • Molecules and Cells
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    • 제26권5호
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    • pp.436-442
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    • 2008
  • Osteoclasts are multinucleated cells with the unique ability to resorb bone. Elevated activity of these cells under pathologic conditions leads to the progression of bone erosion that occurs in osteoporosis, periodontal disease, and rheumatoid arthritis. Thus, the regulation of osteoclast apoptosis is important for bone homeostasis. In this study, we examined the effects of the Janus tyrosine kinase 2 specific inhibitor AG490 on osteoclast apoptosis. We found that AG490 greatly inhibited osteoclast apoptosis. AG490 stimulated the phosphorylation of Akt and ERK. Adenovirus-mediated expression of dominant negative (DN)-Akt and DN-Ras in osteoclasts inhibited the survival of osteoclasts despite the presence of AG490. Cytochrome c release during osteoclast apoptosis was inhibited by AG490 treatment, but this effect was inhibited in the presence of LY294002 or U0126. AG490 suppressed the pro-apoptotic proteins Bad and Bim, which was inhibited in osteoclasts infected with DN-Akt and DN-Ras adenovirus. In addition, constitutively active MEK and myristoylated-Akt adenovirus suppressed the cleavage of pro-caspase-9 and -3 and inhibited osteoclast apoptosis induced by etoposide. Taken together, our results suggest that AG490 inhibited cytochrome c release into the cytosol at least partly by inhibiting the pro-apoptotic proteins Bad and Bim, which in turn suppressed caspase-9 and -3 activation, thereby inhibiting osteoclast apoptosis.

Janus Kinase 2 Inhibitor AG490 Inhibits the STAT3 Signaling Pathway by Suppressing Protein Translation of gp130

  • Seo, In-Ae;Lee, Hyun-Kyoung;Shin, Yoon-Kyung;Lee, Sang-Hwa;Seo, Su-Yeong;Park, Ji-Wook;Park, Hwan-Tae
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권2호
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    • pp.131-138
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    • 2009
  • The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

D.C. 마그네트론 스퍼터링법으로 제조한 ITO 및 ITO/Ag/ITO 박막의 미세조직과 투명 전극 특성 (Microstructure and Properties of ITO and ITO/Ag/ITO Multilayer Thin Films Prepared by D.C. Magnetron Sputtering)

  • 최용락;김선화
    • 한국재료학회지
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    • 제16권8호
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    • pp.490-496
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    • 2006
  • ITO monolayer and ITO/Ag/ITO multilayer thin films are prepared by D.C. magnetron sputtering method. Ag layer was inserted for applying ITO to a flexible substrate at low temperature. Carrier concentration and carrier mobility of ITO and ITO/Ag/ITO thin films were measured, the transmittance of them also was done. The amorphous phase was confirmed to be combined in addition to (400) and (440) peaks from XRD result of ITO thin film. As the substrate temperature increased, the preferred orientation of (400) appeared. From the result of application of Ag layer at room temperature, the growth of columnar structure was inhibited, and the amorphous phase formed mostly. The ITO/Ag/ITO thin film represented the transmittance of above 80% when the thickness of Ag layer was 50 ${\AA}$, and the concentration of carrier increased up to above 10 times than that of ITO thin film. Finally, since very low resistance of 3.9${\Omega}/{\square}$ was observed, the effective application of low temperature process is expected to be possible for ITO thin film.

고주파용 저온 동시소성 세라믹(LTCC)칩 커플러 제조: II. Ag 이온 확산에 대한 소결공정의 영향 (Fabrication of Low Temperature Cofired Ceramic (LTCC) Chip Couplers for High Frequencies ; II. Effect of Sintering Process on Ag Diffusion)

  • 이선우;김경훈;심광보;구기덕
    • 한국세라믹학회지
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    • 제36권5호
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    • pp.490-496
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    • 1999
  • The sintering behavior of LTCC (low temperature cofired ceramics) chip couplers was investigated in relation with Ag diffusion at the interface of glass ceramic substrate-Ag electrode. Sintering temperature was in the range of 825$^{\circ}C$-975$^{\circ}C$. The commercial green sheet and silver electrode were used. Below 875$^{\circ}C$ the diffusion of the Ag ion into the substrate and the penetration of glassy phases into the electrode occurred due to an increase of fluidity. Thus the lectrode line was severely deformed and damaged. At 975$^{\circ}C$ the transformation of crystalline phases into glassy phases and the melting of the Ag electrode resulted in the diffusion of the considerable amount of Ag ions.

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마그놀롤의 HDF세포에서 Nrf2-SOCS3-Jak2-STAT3에 의한 UVB 유래 염증데미지 조절 (The Effect of Magnolol on UVB-induced Inflammation Damage Control via the Nrf2-SOCS3-Jak2-STAT3 Pathway in Human Dermal Fibroblasts)

  • 남영선;지주리
    • 생명과학회지
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    • 제30권10호
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    • pp.867-876
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    • 2020
  • 본 연구는 magnolol에 의한 UVB 유도 세포 손상의 복구를 조사하였다. 우리는 약물재배치를 위해 STAT3 기작을 분석하였고, magnolol HDF 세포에서 세포 생존력을 향상시키며, STAT3의 억제제인 것을 확인하였다. IL-6, UVB 및 IFNγ로 처리 된 HDF 세포는 Jak2 및 인산화 된 STAT3 (p-STAT3)의 높은 발현을 나타냈다. Magnolol 의 처리는 UVB 유도 세포에서 Jak2 및 p-STAT3의 발현을 감소시킬 수 있었다. 또한, UVB- 손상된 세포 성장은 용량 의존적 방식으로 재 활성화 및 magnolol 과의 상관 관계가 상당히 증가되었다. UVB 처리 된 HDF 세포에 대한 AG490 (Jak2 억제제) 처리와 비교하여, 세포 증식이 유의하게 증가 하였다. 우리는 AG490 및 magnolol 이 TNF-α 농도를 감소시키는 것을 확인했다. Western blot (단백질 수준)은 오직 magnolol 처리 된 세포에서만 Jak2 및 p-STAT3 발현의 감소를 나타냈고, Jak2, p-STAT3 및 SOCS3의 발현은 또한 magnolol 처리한 세포에서만 증가하였다. 세포를 magnolol 및 ML385 (NRF2 억제제)로 동시 처리시 세포 증식 및 NRF2 발현을 감소시켰다. MMP9의 양은 magnolol 및 ML385 로의 처리에 의해 증가되었다. 종합적으로, 이들 결과는 NRF2, SOCS3, Jak2 및 STAT3의 발현을 조절함으로써 UVB 손상 후 세포를 회복시키는데 있어 magnolol의 가능성을 입증한다.

AsGeSeS/Ag 박막에서 Ag의 두께에 따른 홀로그래픽 회절 효율 특성 (The characteristics of holographic diffraction efficiency depend on thickness of Ag in AsGeSeS/Ag thin film)

  • 이정태;이기남;여철호;이영종;정흉배
    • 한국전기전자재료학회:학술대회논문집
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    • 한국전기전자재료학회 2003년도 추계학술대회 논문집 Vol.16
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    • pp.490-493
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    • 2003
  • We have carried out two-beam interference experiment to form holographic grating on amorphous $As_{40}Ge_{10}Se_{15}S_{35}/Ag$ double-layer. In this study holographic grating formed using He-Ne laser(632.8nm) under non-polarization state and p-polarization state and we confirm that the diffraction efficiency depend on thickness of Ag. The diffraction efficiency was obtained by first order intensity. We got the maximum diffraction efficiency that thickness of Ag was $600{\AA}$. The maximum diffraction efficiency was 13.5% in (P:P) polarization state.

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Ag 담지된 LaSrCoFeO3 섬유상 perovskite 촉매의 탄소 입자상 물질의 산화반응 (Ag-Loaded LaSrCoFeO3 Perovskite Nano-Fibrous Web for Effective Soot Oxidation)

  • 이찬민;전유권;황호정;지윤성;권오찬;전옥성;설용건
    • Korean Chemical Engineering Research
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    • 제57권4호
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    • pp.584-588
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    • 2019
  • 디젤엔진 시스템은 미세먼지 배출의 엄격해진 저감/제어 기준을 충족하기 위해서 산화촉매는 매우 중요한 기술 중에 하나이다. 본 연구에서는 효율적인 soot산화의 촉매로 Ag 나노입자가 loading된 $La_{0.6}Sr_{0.4}Co_{0.2}Fe_{0.8}O_3$ 섬유상 web 촉매를 제시하였다. 제조된 촉매는 FE-SEM, EDS mapping, XRD, XPS 분석을 통해 특성을 평가하였다. Soot 산화성능측정결과 Ag의 효율적인 촉매특성과 증가된 soot입자와 표면의 접촉면적으로 인하여 50% 산화온도 평가($T_{50}=490^{\circ}C$)에서 자연적인 산화보다 $151^{\circ}C$ 가속화된 것을 확인하였다. 따라서 Ag가 loading된 촉매와 3차원적인 web 구조는 soot 산화에 효율적인 촉매후보군으로 확인하였다.

Novel Enhanced Flexibility of ZnO Nanowires Based Nanogenerators Using Transparent Flexible Top Electrode

  • 강물결;하인호;김성현;조진우;주병권;이철승
    • 한국진공학회:학술대회논문집
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    • 한국진공학회 2014년도 제46회 동계 정기학술대회 초록집
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    • pp.490.1-490.1
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    • 2014
  • The ZnO nanowire (NW)-based nanogenerators (NGs) can have rectifying current and potential generated by the coupled piezoelectric and semiconducting properties of ZnO by variety of external stimulation such as pushing, bending and stretching. So, ZnO NGs needed to enhance durability for stable properties of NGs. The durability of the metal electrodes used in the typical ZnO nanogenerators(NGs) is unstable for both electrical and mechanical stability. Indium tin oxide (ITO) is used as transparent flexible electrode but because of high cost and limited supply of indium, the fragility and lack of flexibility of ITO layers, alternatives are being sought. It is expected that carbon nanotube and Ag nanowire conductive coatings could be a prospective replacement. In this work, we demonstrated transparent flexible ZnO NGs by using CNT/Ag nanowire hybrid electrode, in which electrical and mechanical stability of top electrode has been improved. We grew vertical type ZnO NW by hydrothermal method and ZnO NW was coated with hybrid silicone coating solution as capping layer to enhance adhesion and durability of ZNW. We coated the CNT/Ag nanowire hybrid electrode by using bar coating system on a capping layer. Power generation of the ZnO NG is measured by using a picoammeter, a oscilloscope and confirmed surface condition with FE-SEM. As a results, the NGs using the CNT/Ag NW hybrid electrode show 75% transparency at wavelength 550 nm and small change of the resistance of the electrode after bending test. It will be discussed the effect of the improved flexibility of top electrode on power generation enhancement of ZnO NGs.

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The Role of Janus Kinase in Superoxide-mediated Proliferation of Diabetic Vascular Smooth Muscle Cells

  • Lee, Ji-Young;Park, Ji-Young;Kim, Chi-Dae
    • The Korean Journal of Physiology and Pharmacology
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    • 제11권1호
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    • pp.31-36
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    • 2007
  • To elucidate a potential molecular link between diabetes and atherosclerosis, we investigated the role of Janus tyrosine kinase(JAK) for NAD(P)H oxidase-derived superoxide generation in the enhanced proliferative capacity of vascular smooth muscle cells(VSMC) of Otsuka Long-Evans Tokushima Fatty(OLETF) rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum(FBS) and superoxide generation with an increased NAD(P)H oxidase activity were observed in diabetic(OLETF) VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated by AG490, JAK2 inhibitor, and PP2, Src kinase inhibitor. Tyrosine phosphorylation of proteins in diabetic VSMC, especially JAK2, was increased compared to control VSMC. Furthermore, the enhanced NAD(P)H oxidase activity in diabetic VSMC was significantly attenuated by AG490 in a dose-dependent manner. Together, these results indicate that the signal pathway which leads to diabetes-associated activation of Src kinase/JAK is critically involved in the diabetic VSMC proliferation through NAD(P)H oxidase activation and superoxide generation.