Oxygen Affinity of Hemoglobin Regulates O2Consumption, Metabolism, and Physical Activity

Abstract

The oxygen affinity of hemoglobin is critical for gas exchange in the lung and O 2 delivery in peripheral tissues. In the present study, we generated model mice that carry low affinity hemoglobin with the Titusville mutation in the ␣-globin gene or Presbyterian mutation in the ␤-globin gene. The mutant mice showed increased O 2 consumption and CO 2 production in tissue metabolism, suggesting enhanced O 2 delivery by mutant Hbs. The histology of muscle showed a phenotypical conversion from a fast glycolytic to fast oxidative type. Surprisingly, mutant mice spontaneously ran twice as far as controls despite mild anemia. The oxygen affinity of hemoglobin may control the basal level of erythropoiesis, tissue O 2 consumption, physical activity, and behavior in mice.

O2release from Hb vesicles evaluated using an artificial, narrow O2-permeable tube: comparison with RBCs and acellular Hbs

“…It has been expected that decreasing O 2 affinity (increasing P 50 ) results in an increase in O 2 unloading. This is supported by the result in a mouse model (31) that RBCs with a high P 50 value show enhanced O 2 release for improved exercise capacity.…”

“…The addition of HbV HSA to RBCs increased the thickness of the RBC-free layer from 2.7 Ϯ 1.7 (100RBC) to 7.0 Ϯ 1.6 m (90HbV HSA /10RBC). This increase was due to preferential flow of smaller particles, HbVs, near the peripheral region of the flow channel (4) and reduction of RBCs (i.e., reduction of hematocrit) (31). Furthermore, the perfusion pressure was increased at a con- stant flow rate, because the addition of the viscous HbV HES and HbV HSA suspensions increased the viscosity of the RBC-free lubricating layer.…”

Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis

“…To detect G6PD activity, an assay kit using a water-soluble tetrazolium salt (WST-8) was used according to the manufacturer's protocol (Dojindo) (20). The oxygen binding ability of hESCderived erythroid cells, human CB, and adult PB was measured with a Hemox analyzer, as reported (21,22). Statistical Analysis.…”

Oxidative Stress Causes Heart Failure with Impaired Mitochondrial Respiration

“…Analysis of Physical and Cardiac Contractile ActivitiesMice were voluntarily exercised using a running wheel apparatus (KI-101; Aptec, Kyoto, Japan) as described previously (28). The rotarod task was analyzed using a rotarod apparatus (MK-630; Muromachi Kikai, Tokyo, Japan).…”