Red cell oxygen affinity in fetal sheep: role of 2,3-DPG and adult hemoglobin

1978 ◽  
Vol 45 (1) ◽  
pp. 7-10 ◽  
Author(s):  
H. Bard ◽  
J. C. Fouron ◽  
J. E. Robillard ◽  
A. Cornet ◽  
M. A. Soukini

Studies were carried out during fetal life in sheep to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the switchover to adult hemoglobin synthesis in regulating the position of the fetal red cell oxygen-affinity curve in utero. Adult hemoglobin first appeared near 120 days of gestation. The mean oxygen tension at which hemoglobin is half saturated (P50) prior to 120 days of gestation remained constant at 13.9 +/- 0.3 (SD) Torr and then increased gradually as gestation continued, reaching 19 Torr at term. During the interval of fetal life studied, the level of DPG was 4.43 +/- 1.63 (SD) micromol/g Hb and the deltapH between plasma and red blood cells was 0.227 +/- 0.038 (SD); neither was affected by gestational age. The decrease in the red cell oxygen affinity after 120 days of gestation ocrrelated with the amount of adult hemoglobin present in the fetus (r = 0.78; P less than 0.001). This decrease can be attributed only to the amount of the adult-type hemoglobin present, and not to DPG, or to changes in the deltapH between plasma and red blood cells, because both remained stable during the last trimester.

1993 ◽  
Vol 264 (3) ◽  
pp. R481-R486
Author(s):  
F. R. Ragsdale ◽  
R. L. Ingermann

Pregnancy in Crotalus viridis oreganus is associated with an increase in the nucleoside triphosphate (NTP) concentration and a concomitant decrease in the oxygen affinity of the adult red blood cell. However, although the red blood cells of non-pregnant adults and fetuses have indistinguishable NTP concentrations, they have different oxygen affinities. Therefore, red blood cell NTP concentrations alone cannot account for the oxygen-affinity difference between fetal and maternal red blood cells. Hemoglobins from adult and fetal snakes had similar intrinsic oxygen affinities; however, adult hemoglobin was more responsive to organic phosphate modulation compared with fetal hemoglobin. Structural differences, indicated by native gel electrophoresis and electrophoresis of the globins under denaturing conditions at high pH, corroborated functional differences of hemoglobins from fetus and adult. Therefore, the biochemical basis for the oxygen-affinity difference between maternal and fetal red blood cells in this rattlesnake appears to be unique. It appears to be caused by a functionally distinct fetal hemoglobin and the pregnancy-associated rise in red blood cell NTP levels in the mother.


Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 463-467 ◽  
Author(s):  
STAVROS HAIDAS ◽  
DOMINIQUE LABIE ◽  
JEAN-CLAUDE KAPLAN

Abstract A parallel decline of 2,3-diphosphoglycerate (2,3-DPG) and P50 of intracorpuscular hemoglobin is found in red blood cells during their in vivo aging. After 2,3-DPG depletion due to in vitro storage, the capacity to restore, 2,3-DPG in the presence of inosine is significantly impaired in senescent cells as compared with young cells.


1985 ◽  
Vol 63 (7) ◽  
pp. 804-808 ◽  
Author(s):  
Karin J. Neufeld ◽  
Cindy L. Lederman ◽  
Patrick C. Choy ◽  
Ricky Y. K. Man

The production of arrhythmias in the isolated heart by perfusion with lysophosphatidylcholine has been well documented. However, the role of the lysophospholipid as a physiological factor in the generation of cardiac arrhythmias is not clear. In this study, a pharmacological approach was used to delineate the physiological significance of lysophosphatidylcholine during this cardiac dysfunction. Lidocaine (5–20 mg/L) was found to be effective in the protection of the isolated rat heart from the lysophospholipid-induced arrhythmias at pharmacological concentrations. The effect of lidocaine in the protection of lysophospholipid-induced membrane dysfunction was studied with red blood cells. Lidocaine (2 mg/mL) protected red blood cells from hemolysis in the presence of lysophosphatidylcholine. Lidocaine did not inhibit the binding of the lysophospholipid to the red cell membrane, but inhibited hemolysis in a manner similar to cholesterol. The results are consistent with the postulate that lysophosphatidylcholine is a physiological factor in the pathogenesis of cardiac arrhythmias during myocardial ischemia.


1977 ◽  
Vol 232 (1) ◽  
pp. H79-H84 ◽  
Author(s):  
J. I. Spector ◽  
C. G. Zaroulis ◽  
L. E. Pivacek ◽  
C. P. Emerson ◽  
C. R. Valeri

Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia.


2021 ◽  
Vol 282 ◽  
pp. 03003
Author(s):  
M.A. Derkho ◽  
L.N. Sajfutdinova ◽  
V.K. Strizhikov ◽  
S.V. Strizhikova ◽  
T.A. Ponomaryova

The influence of hen layer density on the variability of the number of red blood cells, heterophiles and lymphocytes in the blood, the secretory activity of adrenal glands, estimated by the level of corti-costerone and cortisol, as well as the presence of interrelations between hormones and blood cells by calculating complex indices, were studied. Chickens, as the research object, were kept in cages, under conditions of standard layer density and increased by 1.5 and 2.0 times. We found that chickens adapt to an increase in layer density by one and a half times, pro-vided that egg production decreases to 33.33%; two times exceed of the regulatory requirements for laying does not correspond to the adaptive abilities of birds. Depending on the level of layer density excess (stress factor) in chicken blood, the concentration of corticosterone and cortisol increases, determining a decrease in the number of lymphocytes and an in-crease in heterophiles against the background of the preservation of red blood cells, reflecting the “energy price” of adaptation. Corticosterone af-fects the relationship of red blood cells with lymphocytes and heterophiles, determining the variability of the values of the indices reflecting the ratio of red blood cells and lymphocytes (ISEL), red blood cells and hetero-philes (ISEG), red blood cells, lymphocytes and corticosterone (ISELC), red blood cells, heterophiles and corticosterone (ISEGC) and the integral index of red blood cells-heterophiles-lymphocytes and corticosterone (IIEGLC).


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1312-1312
Author(s):  
Grant C. Bullock ◽  
Lorrie L. Delehanty ◽  
Anne-Laure A Talbot ◽  
Chante Richardson ◽  
Adam Goldfarb

Abstract Abstract 1312 Anemia affects the quality of life and the life expectancy of millions of people in the U.S. Many patients are either intolerant or unresponsive to available treatments, so alternative strategies are needed. Red blood cell production requires the action of erythropoietin (Epo) on red blood cell precursors in the bone marrow. Iron restriction results in loss of Epo-responsiveness and anemia, despite increased serum Epo levels. Iron infusion restores Epo-responsiveness suggesting that iron dominantly regulates Epo-receptor (EpoR) signaling. Understanding how iron restriction regulates EpoR signaling pathways has major clinical significance. Agonists could offer an iron-free approach that enhances the response to Epo in anemia due to iron deficiency or chronic diseases. In addition, antagonists could be used to treat polycythemia vera or other myeloproliferative disorders. We have discovered that the aconitases, multifunctional iron-sulfur cluster proteins that convert citrate into isocitrate are key in connecting iron to Epo-signaling in early erythroid progenitors (GC Bullock, et. al. Blood 2010;116:97). We also discovered that isocitrate, the downstream product of aconitase, can enhance the effectiveness of Epo during iron deficiency in vitro and in vivo in mice with IDA. These observations suggest that isocitrate or derivatives of isocitrate that synergize with erythropoiesis stimulating agents (ESAs) have important therapeutic application in the treatment of anemia. Deletion of EpoR in mice is incompatible with life, however mice and humans that express truncated EpoR show increased production of red blood cells. These observations suggest that the distal cytoplasmic domain of the EpoR inhibits production of red cells and may play a critical role in iron deficiency anemia. EpoR mutant mice lacking the distal half of the cytoplasmic domain of the EpoR (EpoR-H mice) and mice with the same EpoR truncation mutation plus an additional mutation of tyrosine 343 (EpoR-HM mice) show near normal levels of steady state erythropoiesis. To determine the role of the distal domain in erythroid suppression during iron deficiency, EpoR-H, EpoR-HM and EpoR-wildtype mice were fed a low iron diet and compared by weekly CBCs and flow cytometry. EpoR-H mutant mice continue to efficiently produce red blood cells during iron deficiency. And this occurs despite a decrease in hemoglobin. EpoR-HM mice produce fewer rbcs than EpoR-H mice, however rbc production by EpoR-HM mice resists the suppressive effects of iron restriction. Similar experiments also suggest that the distal EpoR is necessary for the isocitrate-mediated enhancement of Epo-driven erythropoiesis. In addition to aconitase/isocitrate and the distal EpoR other candidate key signaling components of this Epo-dependent, iron-responsive pathway have been identified in our recent preliminary experiments. These components include specific protein kinase C (PKC) isozymes, AKT1 and ERK1/2. These findings support a new model of iron sensing by aconitase/isocitrate that alters EpoR signaling to decrease red blood cell production and conserve iron when supplies are low. This model fits better than older “heme-deficiency” models because disorders in heme synthesis block red cell differentiation at a later stage. This model also has potential to explain changes seen in other tissues during chronic iron deficiency. Nutritional iron restriction may have unmasked a new role for the distal EpoR in red cell development and implicated new iron-responsive Epo signaling pathways that can be used to develop new therapeutic agonists and antagonists of Epo. Disclosures: No relevant conflicts of interest to declare.


1999 ◽  
Vol 202 (20) ◽  
pp. 2787-2795
Author(s):  
S. Dragon ◽  
C. Carey ◽  
K. Martin ◽  
R. Baumann

In chick embryos, developmental changes of the blood oxygen tension control hemoglobin (Hb) oxygen affinity via modulation of ATP and 2, 3BPG concentrations in red blood cells. Hypoxia, which is a normal developmental condition for late chick embryos, causes a decrease of the red cell ATP concentration (and increase of red cell oxygen affinity) as well as activation of 2,3BPG synthesis via cyclic AMP-dependent signaling. Adenosine and catecholamines have been implicated as signaling substances in these red cell responses. To assess the extent to which adenosine and catecholamines are involved in vivo in the control of red cell ATP/2,3BPG concentrations, day 13 chick embryos were treated for 24 h with adenosine A(2) and/or (β)-adrenergic receptor blockers and red cell ATP and 2,3BPG levels were determined. The data suggest that adaptive effects later in development in chick embryos induced by adenosine and catecholamines are vital. We have also tested whether avian embryos of the free-living, high-altitude, native white-tailed ptarmigan (Lagopus leucurus) alter their organic phosphate pattern in red cells in response to incubation at different altitudes. Embryos incubated at 3600–4100 m decrease their red cell ATP concentration much more rapidly than embryos of the same clutch incubated at 1600 m. From these data it can be inferred that the oxygen affinity of high altitude embryos will be adjusted to the altitude at which the eggs are incubated.


Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Marilyn J. Telen

AbstractA number of lines of evidence now support the hypothesis that vaso-occlusion and several of the sequelae of sickle cell disease (SCD) arise, at least in part, from adhesive interactions of sickle red blood cells, leukocytes, and the endothelium. Both experimental and genetic evidence provide support for the importance of these interactions. It is likely that future therapies for SCD might target one or more of these interactions.


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