Nuclear localization of human spermine oxidase isoforms - possible implications in drug response and disease etiology.

The FEBS Journal
Tracy R Murray-StewartRobert A Casero

Abstract

The recent discovery of the direct oxidation of spermine via spermine oxidase (SMO) as a mechanism through which specific antitumor polyamine analogues exert their cytotoxic effects has fueled interest in the study of the polyamine catabolic pathway. A major byproduct of spermine oxidation is H2O2, a source of toxic reactive oxygen species. Recent targeted small interfering RNA studies have confirmed that SMO-produced reactive oxygen species are directly responsible for oxidative stress capable of inducing apoptosis and potentially mutagenic DNA damage. In the present study, we describe a second catalytically active splice variant protein of the human spermine oxidase gene, designated SMO5, which exhibits substrate specificities and affinities comparable to those of the originally identified human spermine oxidase-1, SMO/PAOh1, and, as such, is an additional source of H2O2. Importantly, overexpression of either of these SMO isoforms in NCI-H157 human non-small cell lung carcinoma cells resulted in significant localization of SMO protein in the nucleus, as determined by confocal microscopy. Furthermore, cell lines overexpressing either SMO/PAOh1 or SMO5 demonstrated increased spermine oxidation in the nucleus, with accompanying ...Continue Reading

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Citations

Jul 6, 2013·Journal of Molecular Evolution·Manuela CervelliPaolo Mariottini
Aug 3, 2011·Amino Acids·Manuela CervelliPaolo Mariottini
Nov 15, 2013·Chemical Research in Toxicology·Anthony E Pegg
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Andrew C GoodwinRobert A Casero
Mar 2, 2013·Biological & Pharmaceutical Bulletin·Koichi TakaoYoshiaki Sugita
Jul 16, 2009·Drug Metabolism Reviews·Alan BoobisKeith Tipton
Jul 16, 2009·IUBMB Life·Anthony E Pegg
Jan 17, 2015·Free Radical Biology & Medicine·Emanuela BonaiutoMaria Luisa Di Paolo
Jan 26, 2010·Essays in Biochemistry·Yi HuangRobert A Casero
Jul 11, 2009·The Biochemical Journal·Robert A Casero, Anthony E Pegg
Oct 15, 2008·The International Journal of Biochemistry & Cell Biology·Manuela CervelliPaolo Mariottini
Aug 16, 2011·Gastroenterology·Rupesh ChaturvediKeith T Wilson
Oct 28, 2016·Journal of Translational Medicine·Lourdes Sánchez-SevillaRolando Hernández-Muñoz
Nov 15, 2017·International Journal of Cancer. Journal International Du Cancer·Otto Phanstiel
Oct 20, 2018·The Journal of Biological Chemistry·Tracy Murray StewartRobert A Casero
Jul 26, 2018·Journal of the American Society of Nephrology : JASN·Yang YangChanglin Mei
Jun 5, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Lidan SunChunyu Cao
Sep 30, 2016·The Biochemical Journal·Tracy R Murray-StewartRobert A Casero
May 25, 2020·Cancer Chemotherapy and Pharmacology·Tracy Murray StewartRobert A Casero
Sep 6, 2018·Nature Reviews. Cancer·Robert A CaseroAnthony E Pegg
Aug 31, 2019·Oxidative Medicine and Cellular Longevity·Anastasiya V SnezhkinaAlexey A Dmitriev
Jun 23, 2019·Cellular and Molecular Life Sciences : CMLS·Francisca Sánchez-JiménezJosé Luis Urdiales
Mar 30, 2019·Frontiers in Nutrition·Bruno Ramos-MolinaRafael Peñafiel
Apr 21, 2018·International Journal of Molecular Sciences·Olga A SmirnovaAlexander V Ivanov
Aug 15, 2013·Molecular Cancer Therapeutics·Tracy Murray-StewartRobert A Casero

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