doi: 10.1161/01.ATV.0000209519.12258.74
© 2006 American Heart Association, Inc.
Brief Reviews |
ATVB In Focus
Nitric Oxide Redux
From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Dr Joseph Loscalzo, Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. E-mail jloscalzo{at}partners.org
Almost 20 years ago, endothelium-derived relaxing factor was identified as nitric oxide,1,2 and since that time, the field has witnessed extraordinary growth and complexity. Biologists now recognize that nitric oxide is a multifunctional molecule with roles in neurotransmission, immune regulation, oxidative metabolism and oxygen delivery, inflammation, and control of cell growth, apoptosis, and necrosis, among others. The central importance of nitric oxide in human biology and pathobiology was recognized by the Nobel Committee in 1998 by their awarding the prize to Robert Furchgott, Louis Ignarro, and Ferid Murad for their seminal contributions to the field.
Among the many mechanisms by which nitric oxide exerts its effects are included its redox activities. In 1992, the year in which nitric oxide was named "molecule of the year" by Science, we summarized the complexity of these redox reactions highlighting the differences among nitrosonium, nitrogen monoxide, and nitroxyl anion as redox-active species and their relevance to biological systems.3 The redox activity of nitric oxide was appreciated by chemists, of course, but gained little attention from biologists until its reaction with superoxide to form peroxynitrite was identified in cellular systems.4 Over the ensuing 15 years, abundant evidence supports the importance of redox biochemistry as the basis for multifaceted biological and pathobiological actions of nitric oxide.
Redox regulation is a general biochemical mechanism for governing cell function and phenotype,5 and its modulation offers a novel approach to pharmacotherapeutics.6 The role of nitric oxide in redox regulation is amply demonstrated in its ability to participate in posttranslational modification of the redox-active thiol proteome to form S-nitrosoproteins,7,8 by its ability to regulate mitochondrial function and cellular redox potential,9,10 and by its role in modulating endoplasmic reticulum stress.11 Furthermore, growing evidence suggests that deficiencies in antioxidant enzymes promote oxidant stress and redox-dependent inactivation of nitric oxide.12
In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, we begin a series of Brief Reviews that provide contemporary perspectives on the redox biochemistry and biology of nitric oxide. In this issue of the journal, the series begins with an overview of the role of nitric oxide in vascular redox regulation by Ullrich and colleagues. Each subsequent review will highlight one of the important redox roles of nitric oxide in the cardiovascular system, including posttranslational modification of the vascular thiol proteome, modulation of mitochondrial function and energetics in the vasculature, promotion of endoplasmic reticulum stress, actions in the pulmonary vasculature as they relate to normal pulmonary vascular responses and pulmonary hypertension, and regulation of oxygen delivery by hemoglobin. This series will, then, provide a state-of-the-art update on the redox-dependent actions of nitric oxide in cardiovascular biology and disease states. It is a topic well worth revisiting as the field continues to be enriched by new and very interesting observations.
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- Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987; 84: 9265–9269.
[Abstract/Free Full Text] - Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987; 327: 524–526.[CrossRef][Medline] [Order article via Infotrieve]
- Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-active forms. Science. 1992; 258: 1898–1902.
[Abstract/Free Full Text] - Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical procution by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990; 87: 1620–1624.
[Abstract/Free Full Text] - Maccarrone M, Ullrich V. Redox regulation in disease and ageing. Cell Death Differ. 2004; 11: 949–951.[CrossRef][Medline] [Order article via Infotrieve]
- Frein D, Schildknecht S, Bachschmid M, Ullrich V. Redox regulation: a new challenge for pharmacology. Biochem Pharmacol. 2005; 70: 811–823.[CrossRef][Medline] [Order article via Infotrieve]
- Stamler JS, Jaraki O, Osborne J, Simon DI, Keaney J, Vita J, Singel D, Valeri CR, Loscalzo J. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci U S A. 1992; 89: 7674–7677.
[Abstract/Free Full Text] - Yang Y, Loscalzo J. S-nitrosoprotein formation and localization in endothelial cells. Proc Natl Acad Sci U S A. 2005; 102: 117–122.
[Abstract/Free Full Text] - Beltran B, Mathur A, Duchen MR, Erusalimsky JD, Moncada S. The effect of nitric oxide on cell respiration: a key to understanding its role in cell survival or death. Proc Natl Acad Sci U S A. 2000; 97: 14602–14607.
[Abstract/Free Full Text] - Walford GA, Moussignac RL, Scribner AW, Loscalzo J, Leopold JA. Hypoxia potentiates nitric oxide-mediated apoptosis in endothelial cells via peroxynitrite-induced activation of mitochondrial-dependent and -independent pathways. J Biol Chem. 2004; 279: 4425–4432.
[Abstract/Free Full Text] - Oyadomari S, Takeda K, Takeguchi M, Gotoh T, Matsumoto M, Wada I, Akira S, Araki E, Mori M. Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc Natl Acad Sci U S A. 2001; 98: 10845–10850.
[Abstract/Free Full Text] - Leopold JA, Loscalzo J. Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol. 2005; 25: 1332–1340.
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