Differences in oxygen-dependent nitric oxide metabolism by cytoglobin and myoglobin account for their differing functional roles

Xiaoping Liu, Jianjing Tong, Joseph R. Zweier, Douglas Follmer, Craig Hemann, Raed S. Ismail, Jay L. Zweier

Research output: Contribution to journalArticle

Abstract

The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an oxygen-dependent manner. In skeletal and cardiac muscle, high concentrations of myoglobin (Mb) function as a potent NO scavenger. However, the Mb concentration is very low in vascular smooth muscle, where low concentrations of cytoglobin (Cygb) may play a major role in metabolizing NO. Questions remain regarding how low concentrations of Cygb and Mb differ in terms of NO metabolism, and the basis for their different cellular roles and functions. In this study, electrode techniques were used to perform comparative measurements of the kinetics of NO consumption by Mb and Cygb. UV/Vis spectroscopic methods and computer simulations were performed to study the reaction of Mb and Cygb with ascorbate (Asc) and the underlying mechanism. It was observed that the initial rate of Cygb3+ reduction by Asc was 415-fold greater than that of Mb3+. In the low [O2] range (0-50 μm), the Cygb-mediated NO consumption rate is ~ 500 times more sensitive to changes in O2 concentration than that of Mb. The reduction of Cygb3+ by Asc follows a reversible kinetic model, but that of Mb3+ is irreversible. A reaction mechanism for Cygb3+ reduction by Asc is proposed, and the reaction equilibrium constants are determined. Our results suggest that the rapid reduction of Cygb by cellular reductants enables Cygb to efficiently regulate NO metabolism in the vascular wall in an oxygen-dependent manner, but the slow rate of Mb reduction does not show this oxygen dependence. The rate of metCygb reduction by Asc is hundreds of times greater than the rate of metMb reduction by Asc. As a result, Cygb regulates the rate of NO catabolism in response to a change in oxygen concentration nearly 500 times more efficiently than Mb, enabling Cygb to efficiently regulate the oxygen-dependent NO metabolism in the vascular wall.

Original languageEnglish (US)
Pages (from-to)3621-3631
Number of pages11
JournalFEBS Journal
Volume280
Issue number15
DOIs
StatePublished - Aug 2013
Externally publishedYes

Keywords

  • cytoglobin
  • metabolism kinetics
  • myoglobin
  • nitric oxide
  • oxygen

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Liu, X., Tong, J., Zweier, J. R., Follmer, D., Hemann, C., Ismail, R. S., & Zweier, J. L. (2013). Differences in oxygen-dependent nitric oxide metabolism by cytoglobin and myoglobin account for their differing functional roles. FEBS Journal, 280(15), 3621-3631. https://doi.org/10.1111/febs.12352