Characterization of the function of cytoglobin as an oxygen-dependent regulator of nitric oxide concentration

Xiaoping Liu, Douglas Follmer, Joseph R. Zweier, Xin Huang, Craig Hemann, Kerui Liu, Lawrence J. Druhan, Jay L. Zweier

Research output: Contribution to journalArticle

Abstract

The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an O2-dependent manner. This regulates NO levels in the vascular wall; however, the underlying molecular basis of this O2-dependent NO consumption remains unclear. While cytoglobin (Cygb) was discovered a decade ago, its physiological function remains uncertain. Cygb is expressed in the vascular wall and can consume NO in an O2-dependent manner. Therefore, we characterize the process of the O2-dependent consumption of NO by Cygb in the presence of the cellular reductants and reducing systems ascorbate (Asc) and cytochrome P450 reductase (CPR), measure rate constants of Cygb reduction by Asc and CPR, and propose a reaction mechanism and derive a related kinetic model for this O2-dependent NO consumption involving Cygb(Fe3+) as the main intermediate reduced back to ferrous Cygb by cellular reductants. This kinetic model expresses the relationship between the rate of O2-dependent consumption of NO by Cygb and rate constants of the molecular reactions involved. The predicted rate of O2-dependent consumption of NO by Cygb is consistent with experimental results supporting the validity of the kinetic model. Simulations based on this kinetic model suggest that the high efficiency of Cygb in regulating the NO consumption rate is due to the rapid reduction of Cygb by cellular reductants, which greatly increases the rate of consumption of NO at higher O2 concentrations, and binding of NO to Cygb, which reduces the rate of consumption of NO at lower O2 concentrations. Thus, the coexistence of Cygb with efficient reductants in tissues allows Cygb to function as an O2-dependent regulator of NO decay.

Original languageEnglish (US)
Pages (from-to)5072-5082
Number of pages11
JournalBiochemistry®
Volume51
Issue number25
DOIs
StatePublished - Jun 26 2012
Externally publishedYes

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Nitric Oxide
Oxygen
Reducing Agents
NADPH-Ferrihemoprotein Reductase
Kinetics
cytoglobin
Blood Vessels
Rate constants
Tissue
Vasodilator Agents
Reproducibility of Results

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, X., Follmer, D., Zweier, J. R., Huang, X., Hemann, C., Liu, K., ... Zweier, J. L. (2012). Characterization of the function of cytoglobin as an oxygen-dependent regulator of nitric oxide concentration. Biochemistry®, 51(25), 5072-5082. https://doi.org/10.1021/bi300291h

Characterization of the function of cytoglobin as an oxygen-dependent regulator of nitric oxide concentration. / Liu, Xiaoping; Follmer, Douglas; Zweier, Joseph R.; Huang, Xin; Hemann, Craig; Liu, Kerui; Druhan, Lawrence J.; Zweier, Jay L.

In: Biochemistry®, Vol. 51, No. 25, 26.06.2012, p. 5072-5082.

Research output: Contribution to journalArticle

Liu, X, Follmer, D, Zweier, JR, Huang, X, Hemann, C, Liu, K, Druhan, LJ & Zweier, JL 2012, 'Characterization of the function of cytoglobin as an oxygen-dependent regulator of nitric oxide concentration', Biochemistry®, vol. 51, no. 25, pp. 5072-5082. https://doi.org/10.1021/bi300291h
Liu, Xiaoping ; Follmer, Douglas ; Zweier, Joseph R. ; Huang, Xin ; Hemann, Craig ; Liu, Kerui ; Druhan, Lawrence J. ; Zweier, Jay L. / Characterization of the function of cytoglobin as an oxygen-dependent regulator of nitric oxide concentration. In: Biochemistry®. 2012 ; Vol. 51, No. 25. pp. 5072-5082.
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