Abstract 14875: Cytoglobin but not Myoglobin Senses Hypoxia and Regulates NO Consumption Rate in the Vascular Wall
The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an O2-dependent manner. This O2-dependent NO consumption acts as an O2 sensor changing NO diffusion distance, thus regulating vascular tone. However, the molecular mechanism for this O2 sensor is unknown. Cytoglobin (Cygb) was discovered 10 years ago, and its main physiological function remains uncertain although several have been proposed. We have recently demonstrated that, in the low [O2] range (0-50 μM), Cygb with cellular reductants efficiently regulated the NO consumption rate in response to changes in O2 concentration. In this study, we compared the rate of NO metabolism by Cygb with myoglobin (Mb) and studied their reaction kinetics using electrode techniques and UV/VIS spectroscopic methods. It was observed that the initial rate of Cygb(Fe3+) reduction by ascorbate (Asc) was 410-fold greater than that of Mb(Fe3+). The reduction of Mb(Fe3+) by Asc is irreversible; however, the reduction of Cygb(Fe3+) by Asc follows a reversible kinetic model, and a Cygb-Asc complex is likely involved as an intermediate. At low O2 levels ([O2]=10 μM), prior addition of NO into solutions containing Cygb and ascorbate decreased the NO decay rate of subsequent additions of NO by more than 40%; however, no appreciable changes in the rate of NO decay by Mb were observed under the same experimental conditions. Computer simulations to experimental data showed that in the low [O2] range (0-50 μM), the Cygb-mediated NO consumption rate is nearly 500 times more sensitive to changes in O2 concentration than that the Mb mediated NO consumption rate. These results further confirm that the high efficiency of Cygb in the transduction of [O2] into the NO consumption rate results from the rapid reduction of Cygb, which largely increases the NO consumption rate at higher [O2]; and the NO binding to Cygb, which greatly reduces the NO consumption rate at lower [O2]. This unique property in regulation of the O2-dependent NO consumption enables Cygb to regulate the NO diffusion distance in response to local [O2] changes by using cellular Asc.
- © 2012 by American Heart Association, Inc.