scholarly journals Glycolysis and Lactate Dehydrogenase A in Iron-Mediated Suppression of Osteoblast Function

2020 ◽  
Vol 3 ◽  
Author(s):  
Pete Hunter ◽  
Daniel Edwards ◽  
Christopher Miller ◽  
Erica Clinkenbeard
Keyword(s):  
Bone Marrow ◽  
Lactate Dehydrogenase ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Deficiency Anemia ◽  
Bone Homeostasis ◽  
Western Blots ◽  
Osteoblast Function

Background/Objective:   An estimated 37 million Americans have Chronic Kidney Disease (CKD), a condition in characterized by gradual decline in kidney function1. Patients with CKD are often afflicted with skeletal fractures, increasing morbidity and mortality. CKD has also shown a strong correlation with iron-deficiency anemia. The underlying mechanisms of how iron-deficiency anemia of CKD affects bone loss are not well understood. Based on RNA-sequencing results, we hypothesize that lactate dehydrogenase A (LDHA) may play a role in iron-deficiency mediated suppression of osteoblast differentiation and function.    Methods:   Mouse Progenitor Cells (MPC2) were incubated in osteogenic media along with deferoxamine (DFO) to induce differentiation in chronic iron deficiency; samples were collected after 7 and 14 days. Quantitative real-time PCR and western blot were used to validate LDHA mRNA and protein levels in DFO treated MPCs versus control cells. RNA levels of osteoblast genes and LDHA were also assessed in a pre-clinical mouse model of CKD.    Results:   In vitro, MPCs cultured in DFO media showed a significant increase of LDHA mRNA at 7 days (p=0.015) and returned to near control levels by day 14. Western blots showed a slight increase of total LDHA protein in DFO treated MPCs at 7 days and a large increase of protein at the 14-day mark (p=0.051). In vivo, CKD bone marrow showed a reduction in osteoblast gene expression (osteocalcin and type 1 collagen; p<0.05). LDHA mRNA expression was increased in CKD mice bone marrow when compared to wild-type mice (p=0.051), suggesting an inverse relationship.    Conclusion and Potential Impact:   Inappropriate activation of glycolysis and LDHA appears to play a role in iron-deficiency mediated suppression of osteoblast function in relation to CKD, both in vitro and in vivo. Further exploration of this relationship could be critical to the development of improved treatment options to maintain bone homeostasis during CKD. 

scholarly journals In Vitro and In Vivo Evaluations of Mesoporous Iron Particles for Iron Bioavailability

2019 ◽  
Vol 20 (21) ◽  
pp. 5291
Author(s):  
Lin ◽  
Wu ◽  
Liao ◽  
Jakfar ◽  
Tang ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Cell Model ◽  
Deficiency Anemia ◽  
Iron Particles ◽  
Standard Drug ◽  
Iron Deficient ◽  
Commercial Iron

Chronic renal failure involving hemodialysis results in blood loss during filtration. Iron deficiency and iron deficiency anemia can result. A compensatory increase in iron dosage has many side effects including discomfort. Elemental iron is a highly-pure iron source, which reduces the frequency of dosages; the solubility decreases with increased particle size or pore size. In this study, synthesized mesoporous iron particles (MIPs) were used to relieve iron deficiency anemia. Their bioavailability was measured in vitro by a Caco-2 cell model and in vivo in iron-deficient rats. In vitro bioavailability of MIPs was examined by measuring ferritin content in the Caco-2 cell model. Iron uptake of MIPs was significantly higher than commercial iron particles, which were less porous. In vivo bioavailability of MIPs was examined by measuring body weight gain and red blood cell-related parameters, compared with the bioavailability of standard drug ferrous sulfate in iron-deficient anemic rats. Finally, average hemoglobin content and hemoglobin regeneration efficiency were significantly higher in anemic rats supplemented with commercial iron particles, compared to anemic controls. In the 28-day oral toxicity test, MIPs were not significantly toxic to rat physiology or tissue histopathology. Thus, MIPs may allow effective recovery of hemoglobin in iron deficiency anemia.

scholarly journals Sideroblasts

Blood ◽  
1954 ◽  
Vol 9 (3) ◽  
pp. 203-213 ◽  
Author(s):  
EUGENE KAPLAN ◽  
WOLF W. ZUELZER ◽  
CLAUDE MOURIQUAND
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Deficiency Anemia ◽  
Red Cell ◽  
Hematologic Disorders ◽  
Normal Individuals ◽  
Blue Stain ◽  
Marrow Cultures

Abstract Bone marrow specimens from a large group of infants and children were studied with the prussian blue stain. Iron-staining granules were present in the normoblasts of all the subjects studied, including normal individuals and those with a large variety of hematologic disorders. The term sideroblast was proposed for normoblasts with nonstaining inclusions. The profound decrease in sideroblasts in iron deficiency anemia and their prompt increase following both iron therapy in vivo and the addition of iron to marrow cultures in vitro indicated that the estimation of normoblast iron granules provides a sensitive index of the availability of iron. In thalassemia and in lead poisoning, hemoglobindeficient erythrocytes were found despite the presence of abundant iron granules within the normoblasts. The presens of stainable nonhemoglobin iron in red cell precursors is a normal phenomenon and provides a useful adjunct for the study of iron metabolism.

Maturation, iron deficiency, and ligands in enteric radioiron transport in vitro

1963 ◽  
Vol 204 (1) ◽  
pp. 171-175 ◽  
Author(s):  
W. S. Ruliffson ◽  
J. M. Hopping
Keyword(s):  
Ascorbic Acid ◽  
Iron Deficiency ◽  
Iron Absorption ◽  
Deficiency Anemia ◽  
Anaerobic Incubation ◽  
Reverse Effect ◽  
Factors Affecting ◽  
Everted Gut Sac

The effects in rats, of age, iron-deficiency anemia, and ascorbic acid, citrate, fluoride, and ethylenediaminetetraacetate (EDTA) on enteric radioiron transport were studied in vitro by an everted gut-sac technique. Sacs from young animals transported more than those from older ones. Proximal jejunal sacs from anemic animals transported more than similar sacs from nonanemic rats, but the reverse effect appeared in sacs formed from proximal duodenum. When added to media containing ascorbic acid or citrate, fluoride depressed transport as did anaerobic incubation in the presence of ascorbic acid. Anaerobic incubation in the presence of EDTA appeared to permit elevated transport. Ascorbic acid, citrate, and EDTA all enhanced the level of Fe59 appearing in serosal media. These results appear to agree with previously established in vivo phenomena and tend to validate the in vitro method as one of promise for further studies of factors affecting iron absorption and of the mechanism of iron absorption.

In vitro cytokine production in patients with iron deficiency anemia

2004 ◽  
Vol 113 (3) ◽  
pp. 340-344 ◽  
Author(s):  
Michael Bergman ◽  
Hanna Bessler ◽  
Hertzel Salman ◽  
Dimitri Siomin ◽  
Rachel Straussberg ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Cytokine Production ◽  
Deficiency Anemia

Iron Deficiency Anemia: Recovery from in vitro Oxidative Stress

1993 ◽  
Vol 90 (2) ◽  
pp. 94-98 ◽  
Author(s):  
M. Bartal ◽  
D. Mazor ◽  
A. Dvilansky ◽  
N. Meyerstein
Keyword(s):  
Oxidative Stress ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Deficiency Anemia

scholarly journals A Case of Acute Ischemic Stroke Associated with Hookworm Anemia.

2021 ◽  
Author(s):  
Jiang-qiong Ke ◽  
Huicong Huang ◽  
Guangyao Zhou ◽  
Yan Li ◽  
Shengmin Shao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Iron Deficiency ◽  
Cerebral Infarction ◽  
Acute Ischemic Stroke ◽  
Iron Deficiency Anemia ◽  
Deficiency Anemia ◽  
Cerebral Stroke ◽  
Parasitic Diseases ◽  
Normal Brain

Abstract Background: Hookworm disease discovered in a patient presenting with cerebral infarction due to severe iron-deficiency anemia and confirmed by gastroduodenoscopy has not been reported especially with negative stool routine. Case presentation: We report a male patient who presented himself to us with acute cerebral stroke verified as hookworm disease. Routine laboratory tests revealed low Hemoglobin (Hb) concentration but stool routine and occult blood test were normal. Brain magnetic resonance imaging (MRI) showed left-sided parietal-occipital lobe and centrum semiovale (“watershed”) infarction verified the diagnosis of acute ischemic stroke. Bone marrow aspiration showed proliferative bone marrow image with obvious red system hyperplasia. Gastroduodenoscopy discovered adult hematophagic hookworms in the bulb and descending part of duodenum of the patient. A series of conservative drug treatment was initiated and the patient was subsequently treated with albendazole after the gastroduodenoscopy. Twenty-five days later, the patient's physical function improved gradually and he was discharged without neurological deficit. Conclusion: Hookworm disease could be manifest in acute ischemic stroke. It was concluded that patients with severe iron-deficiency anemia should also be examined for rare intestinal parasitic diseases. Screening for these intestinal parasitic diseases in patients presenting with cerebral infarction and anemia could effectively avoid misdiagnosis and make increase the efficacy of treatment.

scholarly journals Iron-Deficiency Anemia Results in Transcriptional and Metabolic Remodeling in the Heart Toward a Glycolytic Phenotype

2021 ◽  
Vol 7 ◽  
Author(s):  
Yu Jin Chung ◽  
Pawel Swietach ◽  
M. Kate Curtis ◽  
Vicky Ball ◽  
Peter A. Robbins ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Cardiac Contraction ◽  
Deficiency Anemia ◽  
Resonance Spectroscopy ◽  
Pyruvate Metabolism ◽  
Iron Deficient ◽  
Metabolic Remodeling

Iron deficiency is the most prevalent micronutrient disorder globally. When severe, iron deficiency leads to anemia, which can be deleterious to cardiac function. Given the central role of iron and oxygen in cardiac biology, multiple pathways are expected to be altered in iron-deficiency anemia, and identifying these requires an unbiased approach. To investigate these changes, gene expression and metabolism were studied in mice weaned onto an iron-deficient diet for 6 weeks. Whole-exome transcriptomics (RNAseq) identified over 1,500 differentially expressed genes (DEGs), of which 22% were upregulated and 78% were downregulated in the iron-deficient group, relative to control animals on an iron-adjusted diet. The major biological pathways affected were oxidative phosphorylation and pyruvate metabolism, as well as cardiac contraction and responses related to environmental stress. Cardiac metabolism was studied functionally using in vitro and in vivo methodologies. Spectrometric measurement of the activity of the four electron transport chain complexes in total cardiac lysates showed that the activities of Complexes I and IV were reduced in the hearts of iron-deficient animals. Pyruvate metabolism was assessed in vivo using hyperpolarized 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate. Hearts from iron-deficient and anemic animals showed significantly decreased flux through pyruvate dehydrogenase and increased lactic acid production, consistent with tissue hypoxia and induction of genes coding for glycolytic enzymes and H+-monocarboxylate transport-4. Our results show that iron-deficiency anemia results in a metabolic remodeling toward a glycolytic, lactic acid-producing phenotype, a hallmark of hypoxia.

Histological Evaluation of Megakaryocytes and Angiogenic Signaling Molecules of Bone Marrow in Experimentally Induced Iron Deficiency Anemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 953-953
Author(s):  
Jessica Garcia ◽  
Peggy Mankin ◽  
Pedro De Alarcon
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Factor Viii ◽  
Iron Deficiency Anemia ◽  
Plasma Levels ◽  
Signaling Molecules ◽  
Histological Evaluation ◽  
Deficiency Anemia ◽  
Deficient Diet ◽  
Iron Deficient

Abstract Iron deficiency Anemia (IDA) induced reactive thrombocytosis occurs in children. The mechanisms involved in this phenomenon are indeterminate. Traditional cytokines involved in megakaryopoiesis such as Thrombopoietin (TPO), IL-6, and IL-11 have not been shown to be associated with this IDA induced thrombocytosis. Recent studies suggest that growth factors and signaling molecules involved in angiogenesis influence the proliferation and/or differentiation of megakaryocytes. A recent study observed that VEGFR1-mediated pathway up-regulates CXCR4 on megakaryocytes, leading to enhanced platelet production via distribution of megakaryocytes. We previously reported a statistically increased serum/plasma levels of FLT-3 and PDGF, but did not find an increase in plasma levels of TPO, VEGF and CXCR4 in an experimentally induced IDA in rats, when compared to control rats. We now present the histological evaluation of megakaryocytes and the expression of angiogenic signaling molecules, VEGF and CXCR4, in bone marrows of control and IDA rats. Six week old male Sprague-Dawley rats with jugular vein cannulas were obtained. Diet for control rats (N=9) and iron deficient diet rats (N=18) had 50 ppm and 7-8 ppm iron in Purina chow respectively. CBC, Iron Panel, and cytokines were drawn at baseline and five weeks later. On day 0, 1.5 mL of blood was drawn from iron deficient diet rats to further induce anemia. Rats were euthanized by CO2 asphyxiation and cardiac puncture. Femurs were collected, decalcified, and embedded in paraffin. Thin sliced sections were obtained to make slides. The slides were stained with hematoxylin and eosin (H&E), and with peroxidase linked anti factor VIII, VEGF, and CXCR4 according to manufacturer's instructions. The slides were evaluated under 40x microscopy. An area of 0.1 mm2 was selected and the numbers of megakaryocytes in the selected area were visually quantitated. Immunoperoxidase stained slides were analyzed using Image J software. When reviewing H&E stained bone marrow slides per 0.1 mm2, control rats contained 4 megakaryocytes, while those from IDA rats contained 11 megakaryocytes (P=0.0001). In Factor VIII stained slides, quantitative analysis of peroxidase stained megakaryocytes in control group contained 49,271 pixels, while staining in the IDA rats was 185,076 pixels (P=0.00002). When the analysis was carried out looking at vessel staining, there was a significant difference between controls (3.6) and IDA (8.5) per 0.1 mm2 (P=0.00001). In the VEGF stained slides, visual analysis of peroxidase stain showed increased intensity of staining per cell in the IDA rats. In the CXCR4 stained slides, visual inspection of the control bone marrows showed a rare small round cell weakly stained while these cells were more frequent and strongly stained in IDA rats. We successfully induced IDA in an animal model with coexisting thrombocytosis. Bone marrow slides in IDA rats documented the expected increase in number of megakaryocytes. In addition, we documented a marked increase in vascular structures of IDA rats. Contrary to our previously reported plasma levels, VEGF intensity of stain was greater within IDA rat megakaryocytes when compared to control rat megakaryocytes. We also documented an increase of CXCR4 in the bone marrows of IDA rats. However, this increase was limited to early stage megakaryocyte development cells suggesting a role during the differentiation process of megakaryocytes. Both our previous report on circulating angiogenic signaling molecules and the current histological data suggest an important role for angiogenesis in the development of IDA induced thrombocytosis. Disclosures No relevant conflicts of interest to declare.

Serum erythropoietin (EST) titers in anemia

Blood ◽  
1981 ◽  
Vol 58 (6) ◽  
pp. 1164-1170 ◽  
Author(s):  
G de Klerk ◽  
PC Rosengarten ◽  
RJ Vet ◽  
R Goudsmit
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Pernicious Anemia ◽  
Iron Deficiency Anemia ◽  
Megaloblastic Anemia ◽  
Hemoglobin Concentration ◽  
Significant Negative Correlation ◽  
Pure Red Cell Aplasia ◽  
Deficiency Anemia ◽  
Mouse Liver Cell

Erythropoietin (ESF) titers were determined in sera from patients with different types of anemia using the fetal mouse liver cell bioassay. An inverse relationship was found between hemoglobin concentration and ESF titer. However, ESF titers differed markedly between patients at comparable degrees of anemia. Several groups of patients were distinguished on the basis of the activity of their erythroid bone marrow. In each of these groups, a significant negative correlation was found between the hemoglobin concentration and the logarithm of the ESF titer. ESF titers in patients with pure red cell aplasia were fourfold higher than those in patients with iron-deficiency anemia and tenfold higher than those in patients with megaloblastic anemia and homozygous sickle cell anemia at comparable hemoglobin concentrations. Following the initiation of specific therapy in patients with pernicious anemia and patients wit iron-deficiency anemia, serum ESF titers were found to decrease prior to any substantial rise in hemoglobin concentrations. In the patients with pernicious anemia, the lowest ESF levels were found 1 day after administration of vitamin B12, whereas in the patients with iron-deficiency anemia, the lowest ESF levels were reached in the second week of oral iron therapy. ON the basis of these data it was concluded that serum ESF titers in anemic patients are not only inversely related to the hemoglobin concentration but also to the activity of the erythroid bone marrow.

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