PL EN


Preferences help
enabled [disable] Abstract
Number of results
2011 | 58 | 2 | 265-267
Article title

In vitro inhibition of topoisomerase IIα by reduced glutathione

Content
Title variants
Languages of publication
EN
Abstracts
EN
In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration of GSH and GSSG on topoisomerase IIα activity in vitro was investigated. GSH (0-10 mM) inhibited topoisomerase IIα in a concentration-dependent manner while GSSG (1-100 µM) had no significant effect. These findings suggest that the GSH/GSSG system could have a potential in vivo role in regulating topoisomerase IIα activity.
Publisher

Year
Volume
58
Issue
2
Pages
265-267
Physical description
Dates
published
2011
received
2011-03-21
revised
2011-04-26
accepted
2011-06-04
(unknown)
2011-06-06
Contributors
author
  • Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
author
  • Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
author
  • Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
author
  • Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
author
  • Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
References
  • Akerboom TP, Bilzer M, Sies H (1982) The relationship of biliary glutathione disulfide efflux and intracellular glutathione disulfide content in perfused rat liver. J Biol Chem 257: 4248-4252.
  • Bates AD, Maxwell A (2007) Energy coupling in type II topoisomerases: why do they hydrolyze ATP? Biochemistry 46: 7929-7941.
  • D'Arpa P, Machlin PS, Ratrie Hr, Rothfield NF, Cleveland DW, Earnshaw WC (1988) cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc Natl Acad Sci USA 85: 2543-2547.
  • Dringen R (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62: 649-671.
  • Frydman B, Marton LJ, Sun JS, Neder K, Witiak DT, Liu AA, Wang H-M, Mao YM, Wu H-Y, Sanders MM, Liu LF (1997) Induction of DNA topoisomerase II-mediated DNA cleavage by B-lapachone and related naphtoquinones. Cancer Res 57: 620-627.
  • Gilbert H (1995) Thiol/disulfide exchange equilibria and disulfide bond stability. Methods Enzymol 251: 8-28.
  • Go YM, Jones DP (2008) Redox compartmentalization in eukaryotic cells. Biochim Biophys Acta 1780: 1273-1290.
  • Isaacs RJ, Davies SL, Sandri MI, Redwood C, Wells NJ, Hickson ID (1998) Physiological regulation of eukaryotic topoisomerase II. Biochim Biophys Acta 1400: 121-137.
  • Jenkins JR, Ayton P, Jones T, Davies SL, Simmons DL, Harris AL, Sheer D, Hickson ID (1992) Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localization of the gene to chromosome 3p24. Nucleic Acids Res 20: 5587-5592.
  • Kaplowitz N, Aw TY, Ookhtens M (1985) The regulation of hepatic glutathione. Annu Rev Pharmacol Toxicol 25: 715-744.
  • Konstantinov YM, Tarasenko VI, Rogozin IB (2001) Redox modulation of the activity of DNA topoisomerases I from carrot (Daucus carota) mitochondria. Dokl Biochem Biophys 377: 82-84. Translated from Dokl. Akad. Nauk. 377, 263-265 (2001).
  • Li Z, Mondragón A, DiGate RJ (2001) The mechanism of type IA topoisomerase-mediated DNA topological transformations. Mol Cell 7: 301-307.
  • Lu SC (1999) Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J 13: 1169-1183.
  • Lu SC (2009) Regulation of glutathione synthesis. Mol Aspects Med 30: 42-59.
  • Meister A (1995) Glutathione methabolism. Methods Enzymol 251: 3-7.
  • Neder K, Marton LJ, Liu LF, Frydman B (1998) Reaction β-lapachone and related naphthoquinones with 2-mercaptoethanol: a biomimetic model of topoisomerase II poisoning by quinones. Cell Mol Biol 44: 465-474.
  • Pastore A, Federici G, Bertini E, Piemonte F (2003) Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta 333: 19-39.
  • Poot M, Teubert H, Rabinovitch PS, Kavanagh TJJ (1995) De novo synthesis of glutathione is required for both entry into and progression of the cell cycle. J Cell Physiol 163: 555-560.
  • Schoeffler AJ, Berger JM ( 2008) DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q Rev Biophys 41: 41-101.
  • Sng J-H, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM (1999) Molecular cloning and charachterizaton of the human topoisomerase IIα and IIβ genes: evidence for isoform evolution through gene duplication. Biochim Biophys Acta 1444: 395-406.
  • Tirumalai RS, Pargellis CA, Landy A (1996) Identification and characterization of the N-ethylmaleimide-sensitive site in l-integrase. J Biol Chem 271: 29599-29604.
  • Tsai-Pfugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC (1988) Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17g 21-22. Proc Natl Acad Sci USA 85: 7177-7181.
  • Wang W, Bellatori N (1998) Endogenous glutathione conjugates: occurrence and biological functions. Pharmacol Rev 50: 335-355.
  • Voehringer DW, McConkey DJ, McDonnell TJ, Brisbay S, Meyn RE (1998) Bcl-2 expression causes redistribution of glutathione to the nucleus. Proc Natl Acad Sci USA 95: 2956-2960.
  • Wu X, Yalowich JC, Hasinoff BB (2011) Cadmium is a catalytic inhibitor of DNA topoisomerase II. J Inorg Biochem 105: 833-838.
  • Wyckoff E, Natalie D, Nolan JM, Lee M, Hsieh T (1989) Structure of the Drosophila DNA topoisomerase II gene. Nucleotide sequence and homology among topoisomerases II. J Mol Biol 205: 1-13.
  • Yakisich JS, Sidén Å, Eneroth P, Cruz M (2001) Disulfiram is a potent inhibitor of DNA topoisomerases. Biochem Biophys Res Commun 289: 586-590.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv58p265kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.