Effect of Inorganic Phosphate on Red Cell Metabolism: In Vitro and In Vivo Studies

1972 ◽  
pp. 145-154 ◽  
Author(s):  
Michael C. Brain ◽  
Robert T. Card
Keyword(s):  
Inorganic Phosphate ◽  
Cell Metabolism ◽  
In Vivo Studies ◽  
Red Cell ◽  
Red Cell Metabolism

scholarly journals Effect of oxalate and malonate on red cell metabolism

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1389-1393
Author(s):  
E Beutler ◽  
L Forman ◽  
C West
Keyword(s):  
Pyruvate Kinase ◽  
Cell Metabolism ◽  
Inhibitory Effect ◽  
Red Cells ◽  
Red Cell ◽  
Acid Analogue ◽  
2,3 Dpg

The addition of oxalate to blood stored in Citrate-phosphate-dextrose (CPD) produces a marked improvement in 2,3-diphosphoglycerate (2,3-DPG) preservation; an increase in 2,3-DPG levels can also be documented in short-term incubation studies. Oxalate is a potent in vitro inhibitor of red cell lactate dehydrogenase, monophosphoglycerate mutase, and pyruvate kinase (PK). In the presence of fructose 1,6-diphosphate the latter inhibitory effect is competitive with phospho(enol)pyruvate (PEP). Determination of the levels of intermediate compounds in red cells incubated with oxalate suggest the presence of inhibition at the PK step, indicating that this is the site of oxalate action. Apparent inhibition at the glyceraldehyde phosphate dehydrogenase step is apparently due to an increase in the NADH/NAD ratio. Oxalate had no effect on the in vivo viability of rabbit red cells stored in CPD preservatives for 21 days. Greater understanding of the toxicity of oxalate is required before it can be considered suitable as a component of preservative media, but appreciation of the mechanism by which it affects 2,3-DPG levels may be important in design of other blood additives. Malonate, the 3-carbon dicarboxylic acid analogue of oxalate late did not inhibit pyruvate kinase nor affect 2,3-DPG levels.

scholarly journals Effect of oxalate and malonate on red cell metabolism

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1389-1393 ◽  
Author(s):  
E Beutler ◽  
L Forman ◽  
C West
Keyword(s):  
Pyruvate Kinase ◽  
Cell Metabolism ◽  
Inhibitory Effect ◽  
Red Cells ◽  
Red Cell ◽  
Acid Analogue ◽  
2,3 Dpg

Abstract The addition of oxalate to blood stored in Citrate-phosphate-dextrose (CPD) produces a marked improvement in 2,3-diphosphoglycerate (2,3-DPG) preservation; an increase in 2,3-DPG levels can also be documented in short-term incubation studies. Oxalate is a potent in vitro inhibitor of red cell lactate dehydrogenase, monophosphoglycerate mutase, and pyruvate kinase (PK). In the presence of fructose 1,6-diphosphate the latter inhibitory effect is competitive with phospho(enol)pyruvate (PEP). Determination of the levels of intermediate compounds in red cells incubated with oxalate suggest the presence of inhibition at the PK step, indicating that this is the site of oxalate action. Apparent inhibition at the glyceraldehyde phosphate dehydrogenase step is apparently due to an increase in the NADH/NAD ratio. Oxalate had no effect on the in vivo viability of rabbit red cells stored in CPD preservatives for 21 days. Greater understanding of the toxicity of oxalate is required before it can be considered suitable as a component of preservative media, but appreciation of the mechanism by which it affects 2,3-DPG levels may be important in design of other blood additives. Malonate, the 3-carbon dicarboxylic acid analogue of oxalate late did not inhibit pyruvate kinase nor affect 2,3-DPG levels.

In Vitro Studies of Red Cell Metabolism in Haemoglobin H Disease

1970 ◽  
Vol 18 (1) ◽  
pp. 13-28 ◽  
Author(s):  
G. L. Scott ◽  
M. R. Rasbridge ◽  
A. J. GRIMES
Keyword(s):  
Cell Metabolism ◽  
In Vitro Studies ◽  
Red Cell ◽  
Red Cell Metabolism

scholarly journals The Dpg gene: an intracorpuscular modifier of red cell metabolism

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1210-1214 ◽  
Author(s):  
NA Noble ◽  
G Rothstein
Keyword(s):  
Bone Marrow ◽  
Cell Survival ◽  
Cell Metabolism ◽  
Genetic Locus ◽  
Red Cell ◽  
Red Cell Metabolism ◽  
Red Cell Survival ◽  
Long Evans ◽  
Total Body

Abstract The genetic locus designated Dpg has two alleles in outbred Long-Evans rats. Genotype at this locus affects quantities of red cell 2,3- diphosphoglycerate (DPG) and adenosine triphosphate, as well as activities of two important glycolytic enzymes: phosphofructokinase and pyruvate kinase. Intravascular red cell survival is shortened in low- DPG animals. In order to get closer to the specific action of this locus, we addressed the question of whether the Dpg gene acts through intracorpuscular or extracorpuscular factors. Bone marrow transplantation after total body irradiation and 51Cr red cell survival after cross transfusion were the methods used. Because the animals that were used differed in hemoglobin phenotype, donor and recipient cells could be quantified in cross-transplanted animals. Phenotypic markers of Dpg genotype were measured in animals 40 to 50 days after transplantation. Values for these markers correlated highly with the percentage of donor and recipient cells present. In vivo survival of low-DPG red cells was significantly shorter than that of high-DPG cells (P less than .05), regardless of the genotype of the recipient. From the present studies, we conclude that the action of the Dpg gene is exerted by an intracorpuscular factor.

Sodium Pertechnetate as a Red Cell Label: In Vitro and In Vivo Studies

1976 ◽  
Vol 32 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Peter Schmidt ◽  
Hans-Peter Lohrmann ◽  
Hermann Heimpel
Keyword(s):  
In Vivo Studies ◽  
Red Cell ◽  
Sodium Pertechnetate

Rejuvenation of Aged Human Red Cells Improves Their in Vivo Recovery in a Mouse Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 991-991
Author(s):  
Monique GelderMan-Fuhrmann ◽  
Jaroslav G. Vostal
Keyword(s):  
Mouse Model ◽  
Red Cells ◽  
In Vivo Studies ◽  
Red Cell ◽  
Fresh Rbcs ◽  
Gamma Irradiated ◽  
In Vivo Recovery ◽  
Human Rbcs

Evaluation of novel storage or processing technology for human red blood cells (RBCs) involves in vitro tests on the red cells to determine biochemical changes and in vivo studies in healthy human volunteers with radiolabeled red cells to determine in vivo recovery 24 hours post infusion. In vivo studies are needed because our understanding of red cell storage lesions is not sufficient to identify an in vitro test(s) that would adequately predict red cell performance in vivo. The clinical studies with radiolabeled cells are used as the gold standard for evaluation prior to approval of a novel technology by the FDA. However, in vivo studies require time and funds and can be a significant hurdle in the development of new products. An animal model that could predict performance of human red cells in vivo would be useful in the development process. We previously reported that severe combined immunodeficient (SCID) mice could be used as a model to identify damaged human platelets (Transfusion. 47(8):1540–9, 2007). In the current study, we investigated if this murine model could be used to distinguish between the recovery of fresh and aged human RBCs, non-rejuvenated and rejuvenated aged RBCs, gamma-irradiated (25 Gy) fresh RBCs and irradiated fresh RBCs and stored for 28 days. “Fresh” RBCs were processed from whole blood within 24 hrs of collection and the “aged” RBCs were either RBC products stored for 42 or 100 days in an additive solution at 4°C. For in vivo recovery, approximately 1x109 human RBCs were injected into the tail vein of SCID mice (n=5 or 7 per condition) and serial blood samples were collected. Human RBCs were detected in mouse whole blood by flow cytometry using an anti-human glycophorin A mAb (clone CLB-ery-1). Recovery was defined as percent of human RBCs in the mouse circulation at 2 hours post infusion. Rejuvenation of cells was accomplished by incubating RBCs for 1 hour with Rejuvesol solution (Table 1). 2,3-DPG Levels (mM/L) Pre- and Post-Rejuvenation Fresh RBCs Aged for 42 Days Aged for 100 Days Control 3.25±0.40 0.17±0.04 0.38 ±0.06 Rejuvenated 8.58±0.82 4.56±0.17 2.31±0.13 Fresh red cells exhibited recovery of 58.4±4.4 % of total cells injected. Aged RBCs showed a reduced in vivo recovery of 35.7±7.3 % and 5.7±1.6 % of total cells injected for 42 and 100 day old RBC, respectively. Gamma-irradiated fresh RBCs and irradiated fresh RBCs stored for 28 days showed a recovery of 66.7±8.6 % and 55±13.2 % respectively, whereas the recovery of control fresh RBCs and control fresh RBCs stored for 28 days showed a recovery of 58.4±4.4 % and 49.1±7.0 % (p=0.44) respectively (Table 2). In VivoRecovery Fresh RBCs Stored for 28 days Aged for 42 Days Aged for 100 Days nd - not determined Control 58.4±4.5 49.1±7.0 35.7±7.3 5.17±1.6 Rejuvenated 52.5±11.5 nd 55.4±7.1 21.3±5.0 Irradiated (25Gy) 66.7±8.6 55±13.2 nd nd Our data indicate that the SCID mouse model can distinguish between fresh and aged red cells and that rejuvenation of the red cells increases intracellular 2,3-DPG levels and in vivo recovery of aged red cells. The SCID mouse model could be used to develop or improve existing methods of red cell storage and processing. The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

Bovine post-parturient haemoglobinuria: effect of inorganic phosphate on red cell metabolism

1985 ◽  
Vol 39 (3) ◽  
pp. 333-339 ◽  
Author(s):  
Xiao-Long Wang ◽  
C.H. Gallagher ◽  
T.J. Mcclure ◽  
V.E. Reeve ◽  
P.J. Canfield
Keyword(s):  
Inorganic Phosphate ◽  
Cell Metabolism ◽  
Red Cell ◽  
Red Cell Metabolism
Sign in / Sign up

Export Citation Format

Share Document