Institut für Pharmazeutische Chemie -
Prof. Dr. Dieter Steinhilber

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Expertise

• Lipid Signaling mit Schwerpunkt Arachidonsäure-Kaskade
  
• Regulation der Genexpression / Arbeiten über nukleäre Rezeptoren und epigenetische Mechanismen
  
• Signaltransduktion / Regulation der Enzymaktivität
  
  

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Methoden und Geräte

• Zellkultur-Techniken
  
• Chromatographie, Proteinreinigung
  
• Immunhistochemie
  
• 2D-Gelelektrophorese
  
• HPLC, Analytik von Eisosanoiden
  
• Zelluläre Assays: Reaktive Sauerstoffspezies, Kinase-Assays, In-Gel-Kinase-Assays,Calciumbestimmungen, verschiedene funktionelle Assays
  
• Analyse der Regulation der Genexpression: PCR-Techniken, Chromatin-Immunopräzipitation, Gelshift-Assay, Reportergen-Assay
  
• Klonierung von cDNA und Expression von Proteinen in eukaryotischen und prokaryotischen Systemen
  
  

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Mitarbeiter:

• Dr. B. Firla (Molekularbiologie/ Nukleäre Rezeptoren)
  
• Dr. A. Lechtken (Molekularbiologie/ Nukleäre Rezeptoren)
  
• Dr. T. Maier (Enzymaktivität/ Pharmakologie)
  
• Dr. O. Rau (Molekularbiologie/ Genexpression)
  
• Dr. B. Sorg (Molekularbiologie/ Genexpression)
  
  

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Publikationen

• Albert D, Pergola C, Koeberle A, Dodt G, Steinhilber D, Werz O: The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes. J Leukoc Biol 2008; 83: 1019-1027.
  
• Schnur N, Seuter S, Katryniok C, Rådmark O, Steinhilber D: The histone deacetylase inhibitor trichostatin A mediates upregulation of 5-lipoxygenase promoter activity by recruitment of Sp1 to distinct GC-boxes. Biochim Biophys Acta 2007; 1771: 1271-1282.
  
• Fischer L, Hornig M, Pergola C, Meindl N, Franke L, Tanrikulu Y, Dodt G, Schneider G, Steinhilber D, Werz O: The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5-lipoxygenase products. Br J Pharmacol 2007; 152: 471-480.
  
• Rådmark O, Werz O, Steinhilber D, Samuelsson B: 5-Lipoxygenase: regulation of expression and enzyme activity. Trends Biochem Sci 2007; 32: 332-341.
  
• Lechtken A, Hörnig M, Werz O, Corvey N, Zündorf I, Dingermann T, Brandes R, Steinhilber D: Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro. Biochem Biophys Res Commun 2007; 358: 890-896.
  
• Seuter S, Väisänen S, Rådmark O, Carlberg C, Steinhilber D: Functional characterization of vitamin D responding regions in the human 5-Lipoxygenase gene. Biochim Biophys Acta 2007; 1771: 864-872.
  
• Franke L, Schwarz O, Müller-Kuhrt L, Hoernig C, Fischer L, George S, Tanrikulu Y, Schneider P, Werz O, Steinhilber D, Schneider G: Identification of natural-product-derived inhibitors of 5-lipoxygenase activity by ligand-based virtual screening. J Med Chem 2007; 50: 2640-2646.
  
• Rakonjac M, Fischer L, Provost P, Werz O, Steinhilber D, Samuelsson B, Rådmark O: Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 production. Proc Natl Acad Sci U S A. 2006; 103: 13150-13155.
  
• Seuter S, Sorg BL, Steinhilber D: The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4. Biochem Biophys Res Commun 2006; 348: 1403-1410.
  
• Aschrafi A, Meindl N, Firla B, Brandes RP, Steinhilber D: Intracellular localization of RORalpha is isoform and cell line-dependent. Biochim Biophys Acta. 2006; 1763: 805-814.
  
• Sorg BL, Klan N, Seuter S, Dishart D, Rådmark O, Habenicht A, Carlberg C, Werz O, Steinhilber D: Analysis of the 5-lipoxygenase promoter and characterization of a vitamin D receptor binding site. Biochim Biophys Acta 2006; 1761: 686-697.
  
• Lechtken A, Zündorf I, Dingermann T, Firla B, Steinhilber D: Overexpression, refolding, and purification of polyhistidine-tagged human retinoic acid related orphan receptor RORalpha4. Protein Expr Purif 2006; 49: 114-120.
  
• Aleksandrov DA, Zagryagskaya AN, Pushkareva MA, Bachschmid M, Peters-Golden M, Werz O, Steinhilber D, Sud'ina GF: Cholesterol and its anionic derivatives inhibit 5-lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells. FEBS J 2006; 273: 548-557.
  
• Dishart D, Schnur N, Klan N, Werz O, Steinhilber D, Samuelsson B, Rådmark O: GC-rich sequences in the 5-lipoxygenase gene promoter are required for expression in Mono Mac 6 cells, characterization of a novel Sp1 binding site. Biochim Biophys Acta 2005; 1738: 37-47.
  
• Franke L, Byvatov E, Werz O, Steinhilber D, Schneider P, Schneider G: Extraction and visualization of potential pharmacophore points using support vector machines: application to ligand-based virtual screening for COX-2 inhibitors. J Med Chem 2005; 48: 6997-7004.
  
• Werz O, Tretiakova I, Michel A, Ulke-Lemee A, Hörnig M, Franke L, Schneider G, Samuelsson B, Rådmark O, Steinhilber D: Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cells. Proc Natl Acad Sci U S A 2005; 102: 13164-13169.
  
• Hörnig C, Albert D, Fischer L, Hörnig M, Rådmark O, Steinhilber D, Werz O: 1-Oleoyl-2-acetylglycerol stimulates 5-lipoxygenase activity via a putative (phospho)lipid binding site within the N-terminal C2-like domain. J Biol Chem 2005; 280: 26913-26921.