Studies on an Inhibitor of Erythropoiesis. II. Inhibitory Effects of Serum from Uremic Rabbits on Heme Synthesis in Rabbit Bone Marrow Cultures

Moriyama, Yoshiaki; Rege, Arvind B.; Fisher, James W.

doi:10.3181/00379727-148-38483

Cited by 35 publications

(17 citation statements)

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“…4). Since we have shown previously that crude uremic serum inhibits normal human CFU-E formation in the same way as fetal mouse liver erythroid colony formation (18), it seems very likely that it is the same inhibitor or a family of chemically related inhibitors which affect human (18), rabbit (15,16), and murine erythroid progenitor cells of both BFU-E and CFU-E type, as well as the heme synthesizing nucleated erythroid cell compartment (14,17).…”

Section: Discussionmentioning

confidence: 99%

“…Uremic sera were found to impair in vitro erythroid progenitor cell growth of both erythroid burst-forming units and erythroid colonyforming units (CFU-E)l in rabbit and huimani marrow cultures (15,16), as well as heme synithesis in caniine bone marrow cultures (14,17).…”

Section: Introductionmentioning

confidence: 99%

“…During the past several years, (an) erythropoiesis inhibiting factor(s) in sera of uremic aniinals (16) and patients with anemia of chronic renial failure (14,15) have been described. Uremic sera were found to impair in vitro erythroid progenitor cell growth of both erythroid burst-forming units and erythroid colonyforming units (CFU-E)l in rabbit and huimani marrow cultures (15,16), as well as heme synithesis in caniine bone marrow cultures (14,17).…”

Section: Introductionmentioning

confidence: 99%

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Identification of Spermine as an Inhibitor of Erythropoiesis in Patients with Chronic Renal Failure

Radtke¹,

Rege²,

Lamarche³

et al. 1981

J. Clin. Invest.

149

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A B S T R A C T Fetal mouse liver and normal human bone marrow cell cultures were used for studies on the inhibition of erythroid colony formation (CFU-E) by sera from anemic patients with end-stage renal failure and the polyamine spermine. Sera from each of eight predialysis uremic anemic patients with end-stage renal failure produced a significant (P < 0.001) inhibition of erythroid colony formation in the fetal mouse liver cell cultures when compared to sera from normal human volunteers. In vivo or in vitro dialysis of the uremic sera with a 3,500-dalton exclusion limit membrane removed the inhibitor from uremic sera. The uremic serum dialysate provided by the membrane fractionation was significantly inhibitory in the erythroid cell cultures. When this dialysate was applied to gel filtration chromatography (Bio-Gel P-2) the inhibitor was found to be in the same molecular weight range as [14C]spermine. The polyamine spermine produced a dose-related inhibition of erythroid colony formation (CFU-E) in fetal mouse liver and normal human bone marrow cultures. Thus, the following evidence is provided that the in vitro inhibitor of erythropoiesis found in chronic renal failure patients' sera is identical with the polyamine spermine: (a) the inhibitor and radiolabeled spermine appeared in identical Bio-Gel P-2 effluent fractions; (b) when spermine was added to normal human sera at concentrations reported in sera of uremic patients, and studied in both the fetal mouse liver cell culture and normal human bone marrow cultures, a dose-related inhibition of erythroid colony Heiz W. Radtke was a Postdoctoral Fellow in the Depart-

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Spermine as an Inhibitor of Erythropoiesis in Patients with Chronic Renal Failure

Radtke¹,

Rege²,

Lamarche³

et al. 1981

J. Clin. Invest.

149

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“…Erythropoietin deficiency [2,3] and hypoproliferative bone marrow [4,5] have been evaluated as princi pal factors of anemia. In the patients with CRF, shortened red blood cell survival [6], changed erythrocyte membrane fluidity [I], increased purine nucleotides [7], and lipid perox idation accompanied by increase malonyldialdehyde con Accepted: February 26.…”

Section: Introductionmentioning

confidence: 99%

Reduced Erythrocyte Defense Mechanisms against Free Radical Toxicity in Patients with Chronic Renal Failure

Durak¹,

Akyol²,

Başeşme

et al. 1994

Nephron

104

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In this study, activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) enzymes were determined in the erythrocytes from patients with chronic renal failure (CRF) and from healthy subjects. In the conservative drug management group and intermittent ambulatory peritoneal dialysis group, CAT activity was lower than in the control group. However, SOD and GSH-Px activities of these groups were not statistically different from the control values. In the continuous ambulatory peritoneal dialysis group and the hemodialysis group, SOD, GSH-Px and CAT activities were lower than control values. In the patient groups, correlation coefficients between the enzyme activities were also found to be different from the control values. Results suggested that enzymatic antioxidant defense mechanisms were suppressed in the erythrocytes from the patients with CRF, in particular in the erythrocytes from those who were under hemodialysis and continuous ambulatory peritoneal dialysis management. It is proposed that reduced antioxidant defense mechanisms in the erythrocytes is one of the important factors leading to peroxidation in the membrane lipid structure of the erythrocytes and thereby to hemolysis and anemia in the patients with CRF.

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“…The findings that when erythrocytes from patients with CRF were given to normal people, the erythrocytes had normal survival times and when erythrocytes from normal people were given to the patients with CRF, they had shortened survival times [35,36] suggest that primary factors responsible for the shortened erythrocyte survival were present in the circulation. Inhibitor substances accumulating in uremia [31], increased serum neuraminidase activity [37], changed erythrocyte membrane fluidity [38], impaired Na-K pump system in the erythrocytes [39] and increased purine/pyrimidine content in uremic hemolysates [40] have all been suggested to contribute to the hemolysis in patients with CRF.…”

Section: Discussionmentioning

confidence: 99%

Oxidant/Antioxidant Status of Erythrocytes from Patients with Chronic Renal Failure: Effects of Hemodialysis

Durak¹,

Kavutçu²,

Çimen³

et al. 2001

Med Princ Pract

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Objective: It has been suggested that oxidative processes may be increased in patients with chronic renal failure (CRF), and that this is a possible factor contributing to the development of anemia and atherosclerosis, characteristic complications of CRF. The aim of this study was to investigate erythrocyte oxidant/antioxidant status in patients with CRF and to elucidate possible effects of hemodialysis on erythrocyte antioxidant system. Methods: Fasting blood samples were obtained from 33 patients with CRF and from 12 healthy controls. Of the patients, 17 subjects were under regular hemodialysis. Values of the activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and antioxidant potential, nonenzymatic superoxide radical scavenger activity (NSSA) and levels of thiobarbituric acid reagent substances (TBARS) were measured in the erythrocytes from both patients and controls. Results: Antioxidant potential and NSSA values were found to be significantly decreased, while TBARS levels were increased in the erythrocytes of patients. SOD activity was found to be unchanged, but GSH-Px and CAT activities were significantly lower in the patient group. Moreover, the erythrocyte TBARS level in the hemodialysis group was higher than in the controls and nonhemodialysis patients. Conclusion: The results suggest that antioxidant potential is reduced due to impaired antioxidant system in erythrocytes from patients with CRF and that oxidant stress causes significant peroxidation. Hemodialysis is determined to further increase oxidative reactions. These changes seem to contribute to the occurrence of some complications of CRF. Therefore, it has been suggested that antioxidant supplementation may give beneficial results for these patients.

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Studies on an Inhibitor of Erythropoiesis. II. Inhibitory Effects of Serum from Uremic Rabbits on Heme Synthesis in Rabbit Bone Marrow Cultures

Cited by 35 publications

References 1 publication

Identification of Spermine as an Inhibitor of Erythropoiesis in Patients with Chronic Renal Failure

Identification of Spermine as an Inhibitor of Erythropoiesis in Patients with Chronic Renal Failure

Reduced Erythrocyte Defense Mechanisms against Free Radical Toxicity in Patients with Chronic Renal Failure

Oxidant/Antioxidant Status of Erythrocytes from Patients with Chronic Renal Failure: Effects of Hemodialysis

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