Catalysis of S-nitrosothiols formation by serum albumin: The mechanism and implication in vascular control

Nitric oxide (NO⋅) is a short-lived physiological messenger. Its various biological activities can be preserved in a more stable form of S-nitrosothiols (RS-NO). Here we demonstrate that at physiological NO⋅ concentrations, plasma albumin becomes saturated with NO⋅ and accelerates formation of low-molecular-weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar catalysis of NO⋅ oxidation in the albumin hydrophobic core and specific transfer of NO+ to LMW thiols. Albumin-mediated S-nitrosylation and its vasodilatory effect directly depend on the concentration of circulating LMW thiols. Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO⋅ and its reactive oxides and controls the dynamics of NO⋅-dependant processes in the vasculature.

[1]  S. Lipton.  Physiology: Nitric oxide and respiration , 2001, Nature.

[2]  D. Gozal,et al.  S-Nitrosothiols signal the ventilatory response to hypoxia , 2001, Nature.

[3]  K. Moore,et al.  Formation of nanomolar concentrations of S-nitroso-albumin in human plasma by nitric oxide. , 2001, Free radical biology & medicine.

[4]  B. Mutus,et al.  Mechanism of transfer of NO from extracellular S-nitrosothiols into the cytosol by cell-surface protein disulfide isomerase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Gross.  Vascular biology: Targeted delivery of nitric oxide , 2001, Nature.

[6]  E. Nudler,et al.  An autocatalytic mechanism of protein nitrosylation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Gladwin,et al.  Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[8]  N. Hogg.  Biological chemistry and clinical potential of S-nitrosothiols. , 2000, Free radical biology & medicine.

[9]  A. Ferro,et al.  S-Nitrosothiols: a class of nitric oxide-donor drugs. , 2000, Clinical science.

[10]  M. Grisham,et al.  Dynamic state of S-nitrosothiols in human plasma and whole blood. , 2000, Free radical biology & medicine.

[11]  B. Kalyanaraman,et al.  Reactions of *NO, *NO2 and peroxynitrite in membranes: physiological implications. , 1999, Free radical research.

[12]  N. Beda,et al.  Micellar catalysis for oxidation of nitric oxide (NO) in the multi‐phase systems in vivo , 1999, FEBS letters.

[13]  Y. Vodovotz,et al.  Detection of S-nitrosothiols by fluorometric and colorimetric methods. , 1999, Methods in enzymology.

[14]  J. Stamler,et al.  Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure , 1998, The Lancet.

[15]  S. Aleryani,et al.  Superoxide-mediated Decomposition of BiologicalS-Nitrosothiols* , 1998, The Journal of Biological Chemistry.

[16]  Xiaoping Liu,et al.  Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. L. Williams.  Nitrosating agents: is peroxynitrite a likely candidate? , 1997, Nitric oxide : biology and chemistry.

[18]  Eric J. Toone,et al.  (S)NO Signals: Translocation, Regulation, and a Consensus Motif , 1997, Neuron.

[19]  S. Tannenbaum,et al.  Kinetics of S-nitrosation of thiols in nitric oxide solutions. , 1996, Chemical research in toxicology.

[20]  A. Holmgren,et al.  S-Nitrosoglutathione Is Cleaved by the Thioredoxin System with Liberation of Glutathione and Redox Regulating Nitric Oxide* , 1996, The Journal of Biological Chemistry.

[21]  J. Joseph,et al.  Mechanism of Nitric Oxide Release from S-Nitrosothiols* , 1996, The Journal of Biological Chemistry.

[22]  J. Loscalzo,et al.  Nitrosation of Tryptophan Residue(s) in Serum Albumin and Model Dipeptides , 1996, The Journal of Biological Chemistry.

[23]  J. Stamler,et al.  Polynitrosylated proteins: characterization, bioactivity, and functional consequences. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Stamler,et al.  S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control , 1996, Nature.

[25]  V. Kharitonov,et al.  Kinetics of Nitrosation of Thiols by Nitric Oxide in the Presence of Oxygen (*) , 1995, The Journal of Biological Chemistry.

[26]  J. Stamler,et al.  In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols. , 1994, The Journal of clinical investigation.

[27]  I. Hanbauer,et al.  Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction. , 1994, Chemical research in toxicology.

[28]  W. Deen,et al.  Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions. , 1994, Chemical research in toxicology.

[29]  S. Snyder,et al.  Nitric oxide: a physiologic messenger molecule. , 1994, Annual review of biochemistry.

[30]  S. Moncada,et al.  The L-arginine-nitric oxide pathway. , 1993, The New England journal of medicine.

[31]  J. Stamler,et al.  NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties. , 1993, The Journal of clinical investigation.

[32]  N. Kaplowitz,et al.  Bidirectional mechanism of plasma membrane transport of reduced glutathione in intact rat hepatocytes and membrane vesicles. , 1992, The Journal of biological chemistry.

[33]  J. Stamler,et al.  Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. P. Jones,et al.  Renal glutathione transport. Characteristics of the sodium-dependent system in the basal-lateral membrane. , 1984, The Journal of biological chemistry.

[35]  L. Ignarro,et al.  Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. , 1981, The Journal of pharmacology and experimental therapeutics.

[36]  G. Ellman,et al.  Tissue sulfhydryl groups. , 1959, Archives of biochemistry and biophysics.