Reactive oxygen and nitrogen species regulate inducible nitric oxide synthase function shifting the balance of nitric oxide and superoxide production.

Archives of Biochemistry and Biophysics
Jian SunJay L Zweier

Abstract

Inducible NOS (iNOS) is induced in diseases associated with inflammation and oxidative stress, and questions remain regarding its regulation. We demonstrate that reactive oxygen/nitrogen species (ROS/RNS) dose-dependently regulate iNOS function. Tetrahydrobiopterin (BH4)-replete iNOS was exposed to increasing concentrations of ROS/RNS and activity was measured with and without subsequent BH4 addition. Peroxynitrite (ONOO(-)) produced the greatest change in NO generation rate, approximately 95% decrease, and BH4 only partially restored this loss of activity. Superoxide (O2(.-)) greatly decreased NO generation, however, BH4 addition restored this activity. Hydroxyl radical ((.)OH) mildly decreases NO generation in a BH4-dependent manner. iNOS was resistant to H2O2 with only slightly decreased NO generation with up to millimolar concentrations. In contrast to the inhibition of NO generation, ROS enhanced O2(.-) production from iNOS, while ONOO(-) had the opposite effect. Thus, ROS promote reversible iNOS uncoupling, while ONOO(-) induces irreversible enzyme inactivation and decreases both NO and O2(.-) production.

References

Jan 1, 1992·Neuron·D S Bredt, S H Snyder
Aug 1, 1992·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·R Dargel
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M W RadomskiS Moncada
Jan 1, 1990·Annual Review of Pharmacology and Toxicology·L J Ignarro
Jul 15, 1988·Biochemical and Biophysical Research Communications·M KelmJ Schrader
Mar 1, 1994·The Biochemical Journal·R G Knowles, S Moncada
Sep 23, 1994·Cell·C Nathan, Q W Xie
Aug 11, 1995·The Journal of Biological Chemistry·Y Xia, J L Zweier
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y XiaJ L Zweier
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·D J Stuehr
May 1, 1997·Chemical Research in Toxicology·A F HühmerC Schöneich
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y Xia, J L Zweier
Aug 26, 1998·The Journal of Biological Chemistry·Y XiaJ L Zweier
Aug 26, 1998·Clinical and Experimental Immunology·K D KrönckeV Kolb-Bachofen
Aug 29, 1998·Archives of Biochemistry and Biophysics·A SamouilovJ L Zweier
Sep 8, 2000·The Journal of Biological Chemistry·C LeeJ L Zweier
Dec 7, 2000·Immunology·T Akaike, H Maeda
May 11, 2002·Current Drug Metabolism·A C F Gorren, B Mayer
Jun 1, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Albert HuismanTon J Rabelink
Jun 6, 2002·The Journal of Biological Chemistry·Koustubh PandaDennis J Stuehr
Nov 29, 2002·Frontiers in Bioscience : a Journal and Virtual Library·Ka Bian, Ferid Murad
Apr 23, 1962·Biochimica Et Biophysica Acta·B van GELDER, E C SLATER
Sep 1, 2004·Histochemistry and Cell Biology·R M Touyz, E L Schiffrin
Sep 24, 2004·Physiological Reviews·Roland Stocker, John F Keaney
Dec 23, 2006·Antioxidants & Redox Signaling·Masao KanekiKyungho Chang
Mar 21, 2007·The Journal of Biological Chemistry·Amandine MaréchalJérôme Santolini
Sep 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Cristian DumitrescuJay L Zweier
Jan 15, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Mark J CrabtreeSteven S Gross
May 20, 2008·Nitric Oxide : Biology and Chemistry·Andreas Weigert, Bernhard Brüne
Mar 10, 2009·ACS Chemical Biology·Gerardo Ferrer-Sueta, Rafael Radi

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Citations

Jul 14, 2012·Parasitology Research·Ayse Basak EnginNeslihan Bukan
Nov 24, 2012·Nutrition Research Reviews·Sébastien LacroixAnil Nigam
Feb 20, 2013·Antioxidants & Redox Signaling·Samuel H H Chan, Julie Y H Chan
Jul 25, 2014·Toxicology and Applied Pharmacology·Manickam KesavanSouvendra Nath Sarkar
Dec 14, 2011·Free Radical Biology & Medicine·Peter R Kvietys, D Neil Granger
Jun 15, 2011·Free Radical Biology & Medicine·Maret G Traber, Jan F Stevens
Jul 6, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Thekra Al-BelooshiHaider Raza
Oct 12, 2012·Thrombosis and Haemostasis·Eileen McNeill, Keith M Channon
Jun 28, 2015·Journal of Molecular and Cellular Cardiology·Lin XieJay L Zweier
Apr 23, 2013·Redox Report : Communications in Free Radical Research·Johanna M GostnerRobert Sucher
Sep 18, 2010·BMB Reports·Hye-Lim Kim, Young Shik Park
Apr 7, 2015·Comprehensive Psychiatry·Do-Hyeong LeeDo-Hyung Kang
Nov 26, 2014·The Journal of Allergy and Clinical Immunology·Jessy S DeshaneDavid D Chaplin
Apr 27, 2016·Free Radical Biology & Medicine·Donald J HirshKay D Bidle
May 25, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Alaa N A FahmiHatem A Salem
Dec 11, 2014·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·C H SantuzziG R Abreu
Jul 14, 2014·Journal of Inorganic Biochemistry·Vladimír BerkaAh-Lim Tsai
May 21, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tze Khee ChanW S Fred Wong
Jun 15, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Péter BencsikPéter Ferdinandy
Feb 4, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Yoshitaka HirookaKenji Sunagawa
Jul 28, 2018·Frontiers in Physiology·Patricia SiquesEduardo Pena
Apr 5, 2020·Archives of Toxicology·Maria-Georgia ȘtefanFelicia Loghin
May 22, 2020·Redox Biology·Benjamin N GantnerMarcelo G Bonini
Oct 19, 2020·International Journal of Biological Macromolecules·Yun-Tao WuTao Zhou
May 4, 2020·European Journal of Pharmacology·Luzia Kalyne Almeida Moreira LealGlauce Socorro de Barros Viana
May 22, 2021·Free Radical Biology & Medicine·David Weissman, Christoph Maack

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