Visit our Expo - Redox and Inflammation signaling 2012

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Session XIV : Transcriptional and translational control Poster XIV, 51 Microtubule interfering agents affect signaling pathways involved in the regulation of cytochrome P450 genes expression. Martin Modriansk., Jitka Ulrichová, and Zden2k Dvo-ák Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Email: oregon@tunw.upol.cz Microtubule interfering agents, such as vincristine, vinblastine, taxol (paclitaxel) etc., are used in human pharmacotherapy as anti-neoplastic drugs. Use of colchicine, a substance displaying the same microtubule disrupting properties, is limited to the treatment of acute gout attacks and familial mediterranean fever. Besides the common feature of tubulin binding these substances share metabolism by cytochromes P450 (CYP). This is the basis for investigations into potential drug-drug interactions on the level of CYP genes expression. All of these microtubule interfering agents restrict the expression of CYP genes regulated by glucocorticoid (GR) and aryl hydrocarbon (AhR) receptors. While this activity may be associated with cell cycle phase, we show that it is independent of the cell cycle status. Therefore microtubule integrity is important for GR and AhR transcriptional activity. ACKNOWLEDGEMENT This research is supported by grant MSM 6198959216 from the Ministry of Education, Youth and Sports of the Czech Republic and grant GACR 303/04/P074 from the Grant Agency of the Czech Republic. - 554 -
Session XIV : Transcriptional and translational control Poster XIV, 52 Immunomorphological analysis of RAGE-receptor expression and NFkB-activation in tissue samples from normal and degenerated intervertebral discs of various ages A. Nerlich (1), B. Bachmeier (2), E. Schleicher (3), H. Rohrbach (1), G. Paesold (4), N. Boos (4) Dept. of Pathology, Academic Hospital Munich-Bogenhausen, Germany, andreas.nerlich@extern.lrz-muenchen.de Dept. of Clinical Chemistry Clin. Biochemistry, Univ. Munich, Germany Dept. Pathobiochemistry, Univ. Tübingen, Germany Spinal Surgery Unit, Orthopaedic Clinic, Univ. Zürich, Switzerland Recent studies provided circumstantial evidence that the activation of the RAGE-receptor by the oxidation-mediated amino acid modification carboxymethyl-lysine (CML) leads to NFkBactivation and translocation into the nucleus. This leads to the up-regulation of the synthesis of extracellular matrix molecules along with matrix degrading enzymes. In consequence, the structure and function of tissue changes. Recent extensive analyses provided good evidence that the age-associated degeneration of the intervertebral disc is closely associated with both the alteration of the extracellular disc matrix and the accumulation of oxidation-mediated CML modification of proteins. Accordingly, pervious own studies have shown significantly enhanced levels of CML associated with disc degeneration. We therefore investigated the pattern of RAGE-expression and NFkB-translocation into the nucleus. For this study, 43 complete cross-sections of complete human lumbar intervertebral discs had been prepared for the immunohistochemical localization of the RAGE-receptor and NFkBexpression (both antibodies: Santa Cruz Biotech., CA, USA). The samples covered an age between fetal (35th weeks of gestation) to senile age (85 years) with well defined macro- and micromorphological features. The amount of positively labelled cells (RAGE) or nuclei (activated NFkB) were evaluated morphometrically by light microscopy in the inner and outer anterior and posterior annulus fibrosus and nucleus pulposus. No significant expression of RAGE and no obvious activation of NFkB (by translocation into the nucleus) were seen in fetal, juvenile and young adolescent discs (until age 13). In senile discs (age 77 – 85 years) RAGE-expression remained elevated, but NFkB activation was absent. In between, variably high numbers of labelled cells/ nuclei were seen with highest values ranging between 25 – c. 50% of cells in the nucleus pulposus for RAGE, and 15 – 60 % of nuclei for NFkB with significant correlation between both parameters. In the anterior and posterior annulus significantly lower values were seen again for both parameters with more pronounced levels in the inner than the outer annulus. This study is the first that described activation of the NFkB system in human klumbar intervertebral discs in vivo. The close correlation between the expression of RAGE and NFkB-activation suggests that the stimulation of RAGE (e.g. by CML) may induce transcription factor activation in this system. The association between expression rates for both parameters and increasing age indicates a potential link between transcription activation and disc degeneration. This may represent an important mechanism inducing changes in both cellular and extracellular structures of the disc, potentially prone to therapeutic intervention. - 555 -
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- 1 - Luxembourg, January 25th to 2
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Table of content PREFACE ..........
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Preface In 1998, we organized the f
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Acknowledgments This meeting has be
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Group B (15h00 - 17h00) Session V.
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- 11 - Exhibition
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Visit our Expo (in alphabetical ord
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Thursday January 26th, 2006 (Early
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Thursday January 26th, 2006 (Evenin
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Regulation of inflammation and gluc
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Saturday January 28th, 2006 (Early
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Oral presentations (by alphabetical
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4: : Lottin S, Vercoutter-Edouart A
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the B-Raf/mitogen-activated/extrace
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Albertini MC, Accorsi A, Citterio B
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AP-1-dependent gene expression in s
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Jaks and cytokine receptors - an in
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The Role of Met-Gab1 Signalling in
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The mammalian tumor suppressor Scri
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SIGNAL TRANSDUCTION BY STRESS-ACTIV
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Title to be announced Caroline Dive
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Mechanisms of DNA methylation in ma
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Blocking the "4 Integrin-Paxillin I
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Regulation of NF-kB-dependent trans
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The immunomodulator AS101 induces g
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Signaling pathways leading to the a
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Boute, N., Jockers, R. and Issad, T
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Jespsen JS, Sorensen MD and Wengel
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8. Nishikawa, H., Kawai, K., Tanaka
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9) Proteome analysis of rat pancrea
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MicroRNA is an anti-apoptotic facto
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Resveratrol inhibits phorbol ester-
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Cross-talk between angiotensin II a
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Multiple role of histamine H 1 rece
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PI3K Targeting by the Beta-GBP Cyto
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D.P. Chopra, R.E. Menard, J. Janusz
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[2] Meijer, L., Flajolet, M. and Gr
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[4] Niemand, C., Nimmesgern, A., Ha
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Oncogenic signaling by mutant p53 M
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activity of the Peroxisome Prolifer
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Restauration of SHIP-1 activity in
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Hypoxia Signaling. Impact on Tumor
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5. Sokolov EI, Zykov KA, Pukhalsky
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HOW ANTITOXIC AND ANTICANCER AGENTS
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Listeria monocytogenes induced Rac1
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Epigenetic Regulation of Stem Cell
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Survey on in vitro cell death induc
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Distinct roles of IRF-3 and IRF-7 i
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Redox-Sensitive Transcription Facto
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Epigenic control of MHC2TA transcri
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Attenuation of MSK1-driven NF-kB ge
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Talking to chromatin: Silencers Sil
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Ubiquitin ligase Smurf1 controls os
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Workshop presentations (by alphabet
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Ambion MicroRNAs (miRNAs) are small
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Organizer: BIOBASE GmbH Date: Janua
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Reliable and efficient gene Knock-d
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Exploring ubiquitin signaling with
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Poster presentations Poster are cla
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Session I : protein domains Poster
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Session II. Receptor signaling and
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Session II : Receptor signaling and
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Session III. Protein kinase cascade
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Session III : Protein kinase cascad
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Session IV. Protein kinase inhibito
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IV. Protein kinase inhibitors: insi
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IV. Protein kinase inhibitors: insi
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V. Phosphatases as key cell signali
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VI. Proteasome degradation pathways
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VI. Proteasome degradation pathways
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Session VII. Stem cell specific cel
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VIII. Inflammation specific signali
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Session IX. Novel compounds targeti
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Session X : Cell death in cancer -
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Session X : Cell death in cancer Po
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Session XI : Cell death and cardiov
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Session XI: Cell death and cardiova
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Session XII : Cell death and neurod
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Session XIII : Cell signaling pathw
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Session XVI : Chemopreventive agent
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Session XVII : Cell signaling in he
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Dr. Nassera Aouali L-1526 Luxembour
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Dr. Giordano Bianchi Clinic of inte
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Mrs. Isabel Burghardt Laboratory of
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Pr. Czeslaw Cierniewski 92-215 Lodz
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Mr. Gustav Nilsonne Department of L
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