Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite

The Journal of Clinical Investigation
Ming-Hui ZouRichard A Cohen

Abstract

Nitric oxide (NO) is produced by NO synthase (NOS) in many cells and plays important roles in the neuronal, muscular, cardiovascular, and immune systems. In various disease conditions, all three types of NOS (neuronal, inducible, and endothelial) are reported to generate oxidants through unknown mechanisms. We present here the first evidence that peroxynitrite (ONOO(-)) releases zinc from the zinc-thiolate cluster of endothelial NOS (eNOS) and presumably forms disulfide bonds between the monomers. As a result, disruption of the otherwise SDS-resistant eNOS dimers occurs under reducing conditions. eNOS catalytic activity is exquisitely sensitive to ONOO(-), which decreases NO synthesis and increases superoxide anion (O(2)(.-)) production by the enzyme. The reducing cofactor tetrahydrobiopterin is not oxidized, nor does it prevent oxidation of eNOS by the same low concentrations of OONO(-). Furthermore, eNOS derived from endothelial cells exposed to elevated glucose produces more O(2)(.-), and, like eNOS purified from diabetic LDL receptor-deficient mice, contains less zinc and fewer SDS-resistant dimers. Hence, eNOS exposure to oxidants including ONOO(-) causes increased enzymatic uncoupling and generation of O(2)(.-) in diabete...Continue Reading

References

Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J S PollockF Murad
Jul 1, 1996·Chemical Research in Toxicology·J S Beckman
Mar 1, 1996·Chemical Research in Toxicology·A F HühmerC Schöneich
Jan 1, 1996·Biochimie·J P PasquetV Ullrich
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
Dec 31, 1997·The Journal of Clinical Investigation·T Michel, O Feron
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·W Maret, B L Vallee
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·C JacobB L Vallee
Apr 29, 1998·Biological & Pharmaceutical Bulletin·J O MoonT Nagano
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·J Vásquez-VivarK A Pritchard
Dec 18, 1998·The Journal of Biological Chemistry·P MartásekB S Masters
Mar 27, 1999·FEBS Letters·G E ArteelH Sies
Sep 10, 1999·The Journal of Biological Chemistry·J Vásquez-VivarB Kalyanaraman
Aug 24, 2000·The Journal of Biological Chemistry·B HemmensB Mayer
Nov 9, 2000·The Journal of Biological Chemistry·J S ScheeleD Magde
Feb 7, 2001·Circulation Research·U HinkT Munzel
Oct 13, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·A J CayatteR A Cohen

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Citations

Feb 27, 2010·Reviews in Endocrine & Metabolic Disorders·Corey E TabitJoseph A Vita
Feb 3, 2005·Current Hypertension Reports·Ivonne H SchulmanLeopoldo Raij
Mar 17, 2007·Current Hypertension Reports·Carlos Mercado, Edgar A Jaimes
Oct 12, 2012·Current Hypertension Reports·Adam R WendeE Dale Abel
Apr 6, 2004·Current Opinion in Pharmacology·Mitsuhiro Yokoyama
Apr 11, 2013·Microvascular Research·Satomi KagotaKazumasa Shinozuka
Jan 2, 2014·Pharmacology & Therapeutics·Lifei TangMark T Ziolo
Dec 11, 2003·Atherosclerosis. Supplements·Karsten Sydow, Thomas Münzel
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kandasam RaviStephen M Black
Mar 7, 2008·Antioxidants & Redox Signaling·Moo Yeol Lee, Kathy K Griendling
Jun 10, 2009·Antioxidants & Redox Signaling·Ehab H SarsourPrabhat C Goswami
Sep 8, 2011·Antioxidants & Redox Signaling·Deepmala AgarwalJoseph Francis
Apr 9, 2011·Antioxidants & Redox Signaling·Tohru Fukai, Masuko Ushio-Fukai
Apr 12, 2012·Cardiovascular Research·Shyamal C BirJincai Luo
Sep 6, 2011·European Heart Journal·Ulrich Förstermann, William C Sessa
Apr 28, 2010·Journal of Cardiovascular Pharmacology·Richard A Cohen, XiaoYong Tong
Jul 28, 2010·Clinical and Experimental Pharmacology & Physiology·Satomi KagotaKazumasa Shinozuka
May 6, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Dhananjay K KaulMary E Fabry
Sep 22, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Yang-Ming YangDong Sun
Jan 15, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Mark J CrabtreeSteven S Gross
Apr 14, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Gonzalo PeluffoRafael Radi
Dec 8, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Fiona D SaundersDaniel L Traber
May 2, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Clarke G TankersleyWayne Mitzner
Oct 30, 2009·American Journal of Physiology. Renal Physiology·Edgar A JaimesLeopoldo Raij
Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
May 23, 2012·International Journal of Vascular Medicine·Gopi Krishna KolluruChristopher G Kevil
Jun 17, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Qian ZhangDavid J R Fulton
Oct 16, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Miao ZhangMing-Hui Zou
Oct 18, 2008·The Journal of Clinical Investigation·Naoki TerasakaAlan R Tall

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