Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transferrin binding to human placental sites was inhibited by the acute-phase proteins alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-MG), whereas haptoglobin, C-reactive protein and ferritin displayed no such effect. In equilibrium saturation binding assays, the effective acute-phase proteins decreased the apparent affinity of the binding sites for transferrin, but the transferrin binding-site density Bmax. was not significantly changed. For instance, the addition of 30 microM alpha 1-AT increased the KD of transferrin from 8.46 +/- 1.51 nM to 21.6 +/- 3.04 nM; the Bmax. values were 1.17 +/- 0.18 pmol/mg of protein and 1.04 +/- 0.25 pmol/mg of protein respectively. In kinetic studies, alpha 1-AT decreased the association rate constant k+1 of the 125I-transferrin-binding-site complex from 2.18(+/- 0.21) x 10(7) M-1.min-1 to 3.99(+/- 0.18) x 10(6) M-1.min-1. In contrast, the dissociation rate constant k-1 was not changed (0.0948 +/- 0.002 min-1, 0.089 +/- 0.0017 min-1). On isoelectric focusing, no alteration in transferrin protein pattern or shift in isoelectric point was detected in the presence of alpha 1-AT. Inhibition of transferrin binding by the acute-phase proteins alpha 1-AT and alpha 2-MG is competitive. Interestingly, inhibition is already present at physiological concentrations. However, full inhibition is only achieved at concentrations above the normal range, which are attained in acute-phase reactions.
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PMID:The hepatic acute-phase proteins alpha 1-antitrypsin and alpha 2-macroglobulin inhibit binding of transferrin to its receptor. 767 93

We examined the effect of treatment with rHuEpo on platelet counts in 61 hemodialysis patients and correlated them with changes in erythropoietic activity, iron status and inflammation. Platelets (10(9)/1) increased from 220 +/- 80 to 245 +/- 102 after 14 days and stabilized at that level up to day 90 (p < 0.0001). The increment was similar in complete or partial responders but was not observed in failures. Serum transferrin receptor (sTfR, a measure of total erythropoiesis) and Het rose much more progressively, but relative platelet increments correlated with relative increases in sTfR and Hct. Relative platelet increments correlated inversely with relative changes of SeFe or transferrin saturation, but not with their absolute values, nor with baseline ferritin or its progressive decrease. Although baseline platelet count was 12% higher in patients with inflammation and correlated with serum haptoglobin, relative increases were similar in patients with or without inflammation. In conclusion, rHuEpo produced a clinically minor but consistent elevation of platelet counts. These modifications were not related primarily to modifications in iron stores, functional iron deficiency, or inflammation, but paralleled the expansion of erythropoietic activity. The results suggest that rHuEpo has a small positive effect on platelet production, but it cannot be ruled out that this could be partially mediated through functional iron deficiency.
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PMID:Effect of recombinant human erythropoietin on platelets in patients with anemia of renal failure: correlation of platelet count with erythropoietic activity and iron parameters. 781 6

Blood serum levels of stage-specific antigens were measured by radioimmunoassay and immunodiffusion methods in patients with acute pyelonephritis at various stages of traditional antibacterial therapy and ultraviolet autoblood irradiation. Under study were ferritin, beta 2-microglobulin, C-reactive protein, transferrin, alpha 2-macroglobulin, and haptoglobin levels. Kinetics of the measured proteins was demonstrated and the possibility of applying their identification to assessment of treatment efficacy shown. The levels of these proteins are shown to be not only indicators of inflammation and destruction in pyelonephritis, but to reflect as well the repair reactions in the body which course most actively when UV irradiation of autoblood is added to multiple-modality treatment schemes.
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PMID:[Serum antigens in the evaluation of the effectiveness of pyelonephritis therapy]. 795 3

Interleukin-1 beta (Il-1 beta), a key cytokine in the acute phase response, elevates hepatic expression of both the heavy (H) and light (L) ferritin subunits without influencing the steady-state levels of either ferritin transcript. Transfection experiments with human hepatoma cells reveal that sequences within the 5' untranslated region (5'UTR) of H-ferritin mRNA confer translational regulation to chimaeric chloramphenicol acetyl transferase (CAT) mRNAs in response to Il-1 beta in the absence of marked changes in CAT mRNA levels. Il-1 beta dependent translational enhancement is mediated by a distinct G + C rich RNA sequence within 70 nucleotides (nt) of the start codon. The upstream Iron Responsive Element RNA stemloop does not confer increased expression to CAT mRNA in Il-1 beta stimulated hepatoma transfectants. A 38 nucleotide consensus sequence within the 5'UTRs of the mRNAs encoding the hepatic acute phase proteins alpha 1-antitrypsin (alpha 1AT), alpha 1-acid glycoprotein (AGP) and haptoglobin (Dente et al., 1985) is similar to sequences in the G + C rich H-ferritin mRNA translational regulatory element. Deletion of three nucleotides from this region of the 61 nt G + C rich element in the H-ferritin mRNA 5' leader eliminates Il-1 beta translational enhancement of the CAT reporter transcripts.
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PMID:Translational enhancement of H-ferritin mRNA by interleukin-1 beta acts through 5' leader sequences distinct from the iron responsive element. 804 31

Heme proteins transport oxygen and facilitate redox reactions. Heme, however, may be dangerous, especially when free in biologic systems. For example, iron released from hemoglobin-derived heme can catalyze oxidative injury to neuronal cell membranes and may be a factor in post-traumatic damage to the central nervous system. We have shown that heme catalyzes the oxidation of low density lipoproteins which can damage vascular endothelial cells. The endothelium is susceptible to damage by oxidants generated by activated phagocytes, and this has been invoked as an important mechanism in a number of pathologies including the Adulte Respiratory Distress Syndrome (ARDS), acute tubular necrosis, reperfusion injury and atherosclerosis. Because of its highly hydrophobic nature, heme readily intercalates into endothelial membranes and potentiates oxidant-mediated damage. This injury is dependent on the iron content of heme and is completely blocked when concomitant hemopexin is added. Ferrohemoglobin, when added to cultured endothelial cells, is without deleterious effects, but if oxidized to ferrihemoglobin (methemoglobin), it greatly amplifies oxidant damage. Methemoglobin, but not ferrohemoglobin, releases its hemes which can then be incorporated into endothelial cells. Cultured endothelial cells, when exposed to methemoglobin but not ferrohemoglobin, cytochrome c or metmyoglobin, potentiate this oxidant injury. Stabilization of the methemoglobin by cyanide, haptoglobin or capture of the heme by hemopexin abrogates this effect. Paradoxically, more prolonged exposure of endothelium to heme or methemoglobin renders them remarkably resistant to oxidant challenge. Endothelium defends itself from heme by induction of the heme degrading enzyme heme oxygenase and the concomitant production of large amounts of the iron binding protein ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. 808 43

To obtain more information on the effects of long-lasting endurance and strength training on the constituents of the blood, several haematological and iron-related parameters were measured at rest in 39 male athletes from the Polish team who participated in the Olympics in Seoul in 1988. The athletes were divided into two groups: endurance-trained subjects (group E, cyclists, canoeists and rowers; n = 22) and strength-trained subjects (group S, wrestlers and judo; n = 17). The control group was composed of untrained male subjects (n = 48). Blood samples were taken from an antecubital vein with the subject at rest for determinations of haemoglobin concentration ([Hb]), packed cell volume (PCV), erythrocyte (RBC) and reticulocyte count, plasma free haemoglobin concentration, haptoglobin concentration, serum iron, transferrin concentration and ferritin concentrations ([Ferr]); red blood cells were used for estimation of glutamato-oxalate transaminase (GOT) activity and free erythrocyte protoporphyrin concentration ([FEP]). The mean [Hb], PVC, RBC measured in the E athletes were significantly lower than in the control group but were comparable to those obtained in the S atheletes. There were no significantly differences in the haematological indices [mean corpuscular volume (MCV), mean copuscular haemoglobin and mean corpuscular haemoglobin concentration] between the groups of atheletes and the control group. A significant increase in reticulocytosis and GOT activity was observed in the endurance-trained athletes. No impairment of erythropoiesis was observed as indicated by several sensitive markers of haemoglobin formation (FEP, MCV and inspection of blood smears) in the athletes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haematological and iron-related parameters of male endurance and strength trained athletes. 837 68

Iron-derived reactive oxygen species are implicated in the pathogenesis of various vascular disorders including atherosclerosis, vasculitis, and reperfusion injury. The present studies examine whether heme, when liganded to physiologically relevant proteins as in hemoglobin, can provide potentially damaging iron to intact endothelium. We demonstrate that reduced ferrohemoglobin, while relatively innocuous to cultured endothelial cells, when oxidized to ferrihemoglobin (methemoglobin), greatly amplifies oxidant (H2O2)-mediated endothelial-cell injury. Drawing upon our previous observation that free heme similarly primes endothelium for oxidant damage, we posited that methemoglobin, but not ferrohemoglobin, releases its hemes that can then be incorporated into endothelial cells. In support, cultured endothelial cells exposed to methemoglobin--in contrast to exposure to ferrohemoglobin, cytochrome c, or metmyoglobin--rapidly increased their heme oxygenase mRNA and enzyme activity, thereby supporting heme uptake; ferritin production was also markedly increased after such exposure, thus attesting to eventual incorporation of Fe. These cellular methemoglobin effects were inhibited by the heme-scavenging protein hemopexin and by haptoglobin or cyanide, agents that strengthen the liganding between heme and globin. If the endothelium is exposed to methemoglobin for a more prolonged period (16 hr), it accumulates large amounts of ferritin; concomitantly, and presumably associated with iron sequestration by this protein, the endothelium converts from hypersusceptible to hyperresistant to oxidative damage. We conclude that when oxidation of hemoglobin facilitates release of its heme groups, catalytically active iron is provided to neighboring tissue environments. The effect of this relinquished heme on the vasculature is determined both by extracellular factors--i.e., plasma proteins, such as haptoglobin and hemopexin--as well as intracellular factors, including heme oxygenase and ferritin. Acutely, if both extra- and intracellular defenses are overwhelmed, cellular toxicity arises; chronically, when ferritin is induced, resistance to oxidative injury may supervene.
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PMID:Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. 841 93

Previous studies have reported erythrocyte macrocytosis in adults and children with Down syndrome (DS), the significance of which remains unclear. We compared hematological parameters of 50 DS children aged 2 to 15 years, divided into three age groups, with those of 68 aged-matched healthy children. Patients with DS had a significantly increased mean corpuscular volume (MCV) and hemoglobin in all groups when compared with the controls. Erythrocyte creatine content, hexokinase (Hk) activity, erythrocyte and serum folates, vitamin B12, haptoglobin, serum iron, and ferritin were tested. All of these parameters were not significantly different from those of the control group. We conclude that macrocytosis may not be an expression of reduced red cell survival but rather of an altered folate remethylation pathway, secondary to enhanced cystathionine beta-synthase (CBS) activity, the gene for which is present on chromosome 21.
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PMID:Hematological studies in children with Down syndrome. 873 44

High prevalence of anemia and iron deficiency state are found among athletes. To determine the influence of sports activities on the hematological state, we have performed hematological tests and examined the iron metabolism, in addition to some serum enzyme activities and some characters of red blood cells before and after exercise in high school boy athletes. The red blood cell count, hemoglobin level, and hematocrit value were significantly lower than those in the non-athletes boy students. The serum ferritin level in the athletes was significantly lower than that in the control group and healthy adults. Iron deficiency anemia was found in 12% of the athletes. The serum haptoglobin level in the athletes was significantly lower than that in the control group and the level before exercise, suggesting intravascular hemolysis, but the serum hemopexin level showed no difference before and after exercise, suggesting that the hemolysis was not so severe. The serum CPK and myoglobin levels showed a significant increase after exercise, but those levels were quite lower than that of muscle diseases. These findings suggest that daily exercise is closely associated with the increased risk of iron deficiency state, particularly in the high school boy athletes. The mechanism of hemolysis in athletes may partly depend on the increased fragility of iron deficiency red blood cells on mechanical strength.
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PMID:[Sport-anemia: studies on hematological status in high school boy athletes]. 874 90

The study investigated the influence of prolonged physical stress during survival training with food and fluid deprivation on the serum concentrations of erythropoietin (EPO). A group of 29 male subjects [mean age 22.2 (SD 2.8) years, height 1.78 (SD 0.06) m, and body mass (m(b)) 73.5 (SD 8.6) kg] were studied for 5 days of multifactorial stress including restricted water intake (11 H2O. day(-1)) and food intake (628 kJ. day(-1)) combined with physical exercise (estimated energy expenditure approximately 24000 kJ.day(-1)) and sleep deprivation (20 h within 5 days). Blood samples were taken before (T1), after 72 h (T2) and 120 h (T3) of physical stress, and after 48 h, (T4) and 72 h (T5) of recovery. The samples were analysed for EPO, and concentrations of serum iron (Fe), haptoglobin (Hapto), transferrin (Trans), ferritin (Fer), haemoglobin (Hb) and packed cell volume (PCV). The m(b) had decreased by 6.77 kg at T3 (P <0.01) and 0.68 kg at T5. The EPO and Hapto decreased during the survival training (P <0.01) and increased during the recovery period (P <0.01). The Fe increased during the survival training (P <0.01) and remained above the control concentrations during recovery (P <0.01). The Hapto decreased during the survival training (P <0.01) and remained below control concentration at T4 and T5 (P <0.01). The Trans decreased continuously over the week (P <0.01). The Fer increased during the survival training (P <0.01) and returned to control concentration at T5. The Hb increased from T1 to T2 (P <0.01) and had decreased significantly at T5 (P <0.01). The PCV increased from T1 to T2 (P <0.01) and remained below control levels afterwards (P <0.01). From our study it was concluded that, in humans, prolonged physical stress with food and fluid deprivation induces a marked EPO decrease, which is followed by a rapid increase during recovery to restore the reduced O2 transport capacity.
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PMID:Erythropoietin in 29 men during and after prolonged physical stress combined with food and fluid deprivation. 886 64


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