Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

See all formats and pricing
More options …
Volume 384, Issue 5


Trichostatin A and Structurally Related Histone Deacetylase Inhibitors Induce 5-Lipoxygenase Promoter Activity

N. Klan / S. Seuter / N. Schnur / M. Jung / D. Steinhilber
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2003.086


5-Lipoxygenase (5-LO) mRNA expression in Mono Mac 6 cells is induced by the histone deacetylase inhibitor trichostatin A (TsA). In order to study the effects of TsA and several structurally related compounds such as MD85, D237 and M232 on 5-LO promoter activity, we have analyzed the response of a 5-lipoxygenase (5-LO) promoter luciferase reporter gene construct to histone deacetylase inhibitors in transiently transfected Mono Mac 6 and HeLa cells. We show that the activity of 5-LO promoter constructs comprising the sequences -778 to +53 and of several successive deletions of the 5-LO promoter is strongly increased upon TsA treatment. The data suggest a significant involvement of histone deacetylases in the regulation of 5-LO gene transcription. The basal activity of the 5-LO promoter strongly depends on the presence of multiple Sp1-binding sites (GC-boxes), five of which are positioned in tandem. Deletion of the five tandemized GCboxes in the 5-LO reporter gene construct revealed that the induction of 5-LO promoter activity by TsA seems to be independent of these GCboxes. Methylation of 5-LO reporter gene constructs by M.HpaII reduced 5-LO promoter activity but did not prevent induction of promoter activity by TsA, although the activated reporter gene activities were lower compared to the unmethylated plasmid, indicating the dominance of methylation over TsA-sensitive histone deacetylation in silencing of the 5-LO gene. The structure-activity data obtained for histone deacetylase inhibitors suggest that this assay system might serve as a cellular screening tool for the development of HDAC inhibitors.

About the article

Published Online: 2005-06-01

Published in Print: 2003-05-15

Citation Information: Biological Chemistry, Volume 384, Issue 5, Pages 777–785, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2003.086.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Meike J. Saul, Florian Groher, Anett B. Hegewald, Michaela Müller-McNicoll, Rolf Marschalek, Beatrix Suess, and Dieter Steinhilber
Prostaglandins & Other Lipid Mediators, 2017
Bianca Gilbert, Khalil Ahmad, Jessica Roos, Christoph Lehmann, Tomohiro Chiba, Sandra Ulrich-Rückert, Leonie Smeenk, Simon van Heeringen, Thorsten J. Maier, Bernd Groner, and Dieter Steinhilber
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2015, Volume 1849, Number 8, Page 1003
K Ahmad, C Katryniok, B Scholz, J Merkens, D Löscher, R Marschalek, and D Steinhilber
Oncogenesis, 2014, Volume 3, Number 11, Page e127
James J. Potter, Xiaopu Liu, Ayman Koteish, and Esteban Mezey
Liver International, 2013, Volume 33, Number 5, Page 677
Laura Pufahl, Careen Katryniok, Nicole Schnur, Bernd L. Sorg, Julia Metzner, Manuel Grez, and Dieter Steinhilber
Journal of Cellular and Molecular Medicine, 2012, Volume 16, Number 7, Page 1461
Kirsten L. Stoffers, Bernd L. Sorg, Sabine Seuter, Oliver Rau, Olof Rådmark, and Dieter Steinhilber
Journal of Molecular Biology, 2010, Volume 395, Number 4, Page 884
Sabine Seuter, Bernd L. Sorg, and Dieter Steinhilber
Biochemical and Biophysical Research Communications, 2006, Volume 348, Number 4, Page 1403
U.P. Kelavkar, N.S. Harya, J. Hutzley, D.J. Bacich, F.A. Monzon, U. Chandran, R. Dhir, and D.S. O’Keefe
Prostaglandins & Other Lipid Mediators, 2007, Volume 82, Number 1-4, Page 185
Dennis Wegener, Christian Hildmann, and Andreas Schwienhorst
Molecular Genetics and Metabolism, 2003, Volume 80, Number 1-2, Page 138
Cheng Liu, Dawei Xu, Jan Sjöberg, Pontus Forsell, Magnus Björkholm, and Hans-Erik Claesson
Experimental Cell Research, 2004, Volume 297, Number 1, Page 61
Olof Rådmark, Oliver Werz, Dieter Steinhilber, and Bengt Samuelsson
Trends in Biochemical Sciences, 2007, Volume 32, Number 7, Page 332
Hans-Jörg Warnatz, Robert Querfurth, Anna Guerasimova, Xi Cheng, Stefan A. Haas, Andrew L. Hufton, Thomas Manke, Dominique Vanhecke, Wilfried Nietfeld, Martin Vingron, Michal Janitz, Hans Lehrach, and Marie-Laure Yaspo
Nucleic Acids Research, 2010, Volume 38, Number 18, Page 6112
Zhijing Zhang, Chang-qing Chen, and Hari Manev
Journal of Neurochemistry, 2004, Volume 88, Number 6, Page 1424
Amitabh Gupta, Rong Hou, Liming Liu, Shungo Hiroyasu, Jennifer A. Hadix, Gordon S. Huggins, and Nicholas E.S. Sibinga
Journal of Cellular Biochemistry, 2009, Volume 107, Number 3, Page 438
Oliver Werz and Dieter Steinhilber
Expert Opinion on Therapeutic Patents, 2005, Volume 15, Number 5, Page 505

Comments (0)

Please log in or register to comment.
Log in