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

Authors

  • Xiaoping Liu,

    Corresponding author
    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
    • Correspondence

      X. Liu and J. L. Zweier, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, 473 West 12th Avenue, Columbus, OH 43210, USA

      Fax: +1 614 292 8778; +1 614 247 7845

      Tel: +1 614 292 1305; +1 614 247 7788

      E-mails: Xiaoping.liu@osumc.edu; jay.zweier@osumc.edu

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  • Jianjing Tong,

    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
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  • Joseph R. Zweier,

    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
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  • Douglas Follmer,

    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
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  • Craig Hemann,

    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
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  • Raed S. Ismail,

    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
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  • Jay L. Zweier

    Corresponding author
    1. Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA
    • Correspondence

      X. Liu and J. L. Zweier, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, 473 West 12th Avenue, Columbus, OH 43210, USA

      Fax: +1 614 292 8778; +1 614 247 7845

      Tel: +1 614 292 1305; +1 614 247 7788

      E-mails: Xiaoping.liu@osumc.edu; jay.zweier@osumc.edu

    Search for more papers by this author

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.

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