• Title/Summary/Keyword: FIH-1

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Novel Dioxygenases, HIF-α Specific Prolyl-hydroxylase and Asparanginyl-hydroxylase: O2 Switch for Cell Survival

  • Park, Hyun-Sung
    • Toxicological Research
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    • v.24 no.2
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    • pp.101-107
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    • 2008
  • Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

Design and deposition of two-layer antireflection and antistatic coatings using a TiN thin film (TiN 박막을 이용한 2층 무반사 코팅의 설계 및 층착)

  • 황보창권
    • Korean Journal of Optics and Photonics
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    • v.11 no.5
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    • pp.323-329
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    • 2000
  • In this study we have calculated an ideal complex refractive index of a TiN trim used in a layer of anl1reilecnon (I\R) coatmg, [air$ISiO_2ITiNIglass$] in the visible. Also we simulated the rellectance of lwo-layer AR coating by varying the thicknesses of TiN and $SiO_2$ layers, respecl1vely. The simolation results show that we can controllhe lowest reflectance and AR band of tile AR coating. The TIN fihns were fabricated by a RF magnetron sputtering apparalus. The chemical, structural and electrical properties of TiN fih11S were inveshgated by the Rutherford backscattering spech'oscopy (RBS), atomic force microscope (AFM) and 4-point probe. The optical properlies were inve,tigated by the spectrophotometer and vanable angle spectroscopic ellipsometer (VASE). The smface roughness of TiN flhns \vas $9~10\AA$. TIle resistivity of TiN films was TEX>$360~730\mu$\Omega $ cm. The ,toichlOllletry of TiN film was 1'1: O:N = I: 0.65 :0.95 and ilic oxygen wa~ found on ilie smface. With these experimental and simu]al1on resulLs, we deposited duo: two-layer AR coating, [air$ISiO_2ITiNIglass$] and the refleClance was under 0.5% ill the regIOn of 440-650 run. 0 run.

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