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)

To investigate how cigarette smoking increases the risk of cardiovascular disease, risk factors were compared between 166 cigarette smokers and 312 non-smokers, in a random sample of males (Chinese, Malays and Asian Indians) aged 30-69 years from the general population of Singapore. There was adjusted for age and ethnic group. The prevalence of hypertension was lower in cigarette smokers (15.2%) than non-smokers (21.9%), with the difference reduced by adjustment for body mass index (BMI). Smokers had: lower mean serum HDL-cholesterol (0.76 versus 0.81 mmol/l) and higher mean serum fasting triglyceride (1.92 versus 1.71 mmol/l), which will increase atherosclerosis; higher mean plasma fibrinogen (2.75 versus 2.67 g/l) and plasminogen activator inhibitor 1 [PAI-1] (24.9 versus 22.2 ng/ml), which will increase thrombosis; and lower mean plasma vitamin C (4.4 versus 6.4 mg/l) and serum selenium (118 versus 123 microg/l), which may increase atherosclerosis. Adjustment for BMI slightly increased the differences for HDL-cholesterol, fasting triglyceride, fibrinogen and PAI-1, indicating that less generalised obesity among smokers reduces their increased cardiovascular disease risk. Smoking was not found to be related to: diabetes mellitus; serum total cholesterol, LDL-cholesterol, apolipoproteins A1 and B and lipoprotein(a); plasma factor VIIc and prothrombin fragment 1 + 2; and plasma vitamins A and E and serum ferritin. There was no evidence of increased insulin resistance in smokers, as measured by mean fasting serum insulin.
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PMID:Cardiovascular risk factors in relation to cigarette smoking: a population-based survey among Asians in Singapore. 962 68

Glucose and amino acid starvation of cells in culture generally enhances their sensitivity to oxidative stress. This is explained by compensatory autophagocytosis, which results in increased amounts of lysosomal low-molecular-weight, redox-active iron, due to the degradation of metallo-proteins, with a potential increase in iron-catalyzed, intralysosomal oxidative reactions. Such reactions diminish the stability of lysosomal membranes, with resultant leakage of hydrolytic enzymes into the cytosol and ensuing cellular degeneration, often of apoptotic type. However, starvation of NIT insulinoma cells, which are normally remarkably sensitive to oxidative stress, actually attenuated the sensitivity to such stress. We found that starved NIT cells rapidly synthesized ferritin. Moreover, ferritin was found to be autophagocytosed, and the lysosomes were stabilized, as assayed by the acridine orange relocation test. We hypothesize that compensatory autophagocytosis during starvation increases the cytosolic pool of redox-active iron, as a reflection of enhanced transportation of low-molecular-weight iron from autophagic lysosomes to the cytosol, resulting in ferritin induction. The newly formed ferritin would, in turn, become autophagocytosed and bind redox-active lysosomal iron in a non-redox-active form. We also suggest that the proposed mechanism may be a way for oxidative stress-sensitive cells to compensate partly for their failing capacity to degrade hydrogen peroxide before it leaks into the acidic vacuolar apparatus and induces intralysosomal oxidative stress. The insulin-producing beta cell may belong to this type of cells.
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PMID:Starvation-induced autophagocytosis paradoxically decreases the susceptibility to oxidative stress of the extremely oxidative stress-sensitive NIT insulinoma cells. 975 30

Insulin and lipid metabolism were studied in seven patients (19+/-1 years) with end-stage renal disease on continuous cycling peritoneal dialysis (CCPD) before and after 6 months of therapy with human recombinant erythropoietin (EPO) to correct anemia. Hematocrit increased from 22.2+/-1.8% to 34.8+/-1.8% (P<0.001) following EPO treatment. Serum ferritin (P<0.05) and serum iron (P<0.01) decreased significantly after anemia correction. There were no significant differences in the height, weight, anthropometric measures, or intakes of protein and total calories in the patients before and after the 6 months of EPO therapy. There were no differences in serum biochemical parameters, including 1,25-dihydroxyvitamin D3 and parathyroid hormone in these patients before and after 6 months of EPO therapy. Residual renal function and Kt/Vurea were also not different before and after 6 months of EPO therapy. The hyperinsulinemic euglycemic clamp technique was used to measure insulin sensitivity. Before EPO, insulin sensitivity was low in patients on CCPD (238+/-19 mg/m2 per min) compared with controls (320+/-30; P<0.01). After 6 months of EPO therapy, insulin sensitivity increased by 28% (305+/-26, P<0.01 vs. pre-EPO values), so that these values were no longer different from control values. The hyperglycemic clamp technique was used to measure insulin secretion. Before EPO, both early- and late-phase insulin secretion were elevated in patients on CCPD compared with controls (P<0.01 in both cases). These indices of insulin secretion decreased significantly (P<0.01) following 6 months of EPO. Before EPO, plasma triglycerides, total cholesterol, low-density lipoprotein, cholesterol, and apolipoprotein B were elevated in patients compared with controls. These lipid concentrations decreased significantly following 6 months of EPO. Thus, treatment of anemia by EPO is associated with improvements in insulin and lipid abnormalities in uremic patients on CCPD.
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PMID:Metabolic effects of erythropoietin in patients on peritoneal dialysis. 981 91

Growth failure is commonly described in polytransfused thalassaemia major patients (Th) with or without growth hormone (GH) releasing hormone-GH axis impairment. We have investigated the efficacy of short-term recombinant GH (rhGH) therapy (Saizen [Serono] 0.1 IU/kg/day 6 evenings/week administered s.c. for 12 months) on growth and predicted final height in 28 (19M, 9F) regularly transfused Th with growth deficiency (aged 14.8 +/- 2.0 yr) on long term desferrioxamine s.c. therapy. All Th had no evidence of congestive heart failure, hypothyroidism or impaired glucose tolerance; in all patients the GH peak (evaluated during both insulin and clonidine test) was < or = 20 mIU/l; hypergonadotropic hypogonadism was excluded in Th with delayed puberty. At the start of therapy height age (HA)/bone age (BA) ratio was 0.92 +/- 0.12. Bone age delay was positively correlated to chronological age (CA), serum ferritin levels (mean of the last three years), the age at the start of chelation therapy, growth velocity calculated for CA during the last year; a positive correlation was also found between circulating IGF-I levels and age at the start of chelation therapy. After 1 year on rhGH therapy there was a significant increase of height calculated for CA (not for BA), of growth velocity calculated for both CA and BA and of circulating IGF-I levels; the HA variation/BA variation ratio was 1.85 +/- 1.71, without any significant difference between predicted final height at the start (-1.08 +/- 1.28 SDS) and at the end of rhGH therapy (-0.88 +/- 1.13). The variation of height calculated for CA was positively correlated to both CA and growth velocity during the last year before rhGH therapy (calculated for CA) and negatively to the height at the start (calculated for CA). There were no side effects and haematological parameters did not show significant changes. In conclusion, our data, obtained in a relatively large group of Th, confirm the emerging results of short-term (12 months) rhGH therapy on growth, as shown by the increase of both growth velocity and height calculated for CA. With regard to final height, although the mean variation of HA/variation of BA ratio was 1.85, no significant increase of the predicted final height was found between the start and the end of rhGH therapy. We are evaluating the effect of long-term rhGH therapy on growth in these patients.
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PMID:Short-term therapy with recombinant growth hormone in polytransfused thalassaemia major patients with growth deficiency. 1009 Nov 55

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.
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PMID:Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. 1066 1

Genetic hemochromatosis (GH) is associated with two mutations of the HFE gene (Cys282Tyr and His63Asp). Heterozygosity for GH is associated with a mild increase in iron metabolism parameters, and increased iron stores are associated with abnormal glucose tolerance and decreased insulin sensitivity in the general population. We have previously shown that the frequency of the two HFE mutations is not increased in patients with type 2 diabetes. However, to assess whether the presence of HFE mutations modulates the clinical presentation of type 2 diabetes, we studied the clinical characteristics and iron metabolism indexes according to the presence of the two mutations in 266 patients with type 2 diabetes. The Cys282Tyr mutation and the His63Asp mutation were present in 9. 8% and 26% of the patients, respectively. Serum iron, transferrin saturation and ferritin concentrations were significantly increased in patients expressing either HFE mutations, compared to those without any mutation. There was no difference in the clinical characteristics in the two groups except that obesity was significantly less frequent in the patients with at least one mutation than in those without any mutation (27.6% vs 42.8%, p=0.02). This finding suggests that, in the absence of obesity, HFE mutations, through the insulin resistance associated with the increase in iron stores, may contribute to the onset of type 2 diabetes.
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PMID:Clinical characteristics of type 2 diabetes in patients with mutations of HFE. 1070 6

In order to study the relationship between the serum ferritin level and the components of the insulin resistance syndrome in type 2 diabetic patients, we evaluated fifty type 2 diabetic patients who were selected according to NDDG/WHO criteria from those patients attending Korea University Hospital from 1997 to 1998. Twenty-five healthy non-diabetic subjects of comparable age and sex distribution acted as a control group. The results showed that the value of log ferritin was higher in the type 2 diabetes patients than the control subjects, but not at a statistically significant level (p = 0.09). Log ferritin was correlated with fasting blood sugar level (r = 0.235, p = 0.048) and body mass index (BMI) (r = 0.285, p = 0.05). In the type 2 diabetic patients, log ferritin was correlated with fasting C-peptide (r = 0.478, p = 0.009). In the control subjects, log ferritin was correlated only with BMI (r = 0.477, p = 0.012). In a stepwise multiple regression analysis, the diabetic group showed a significant correlation between fasting C-peptide and log ferritin (p = 0.001). In the control group, the fasting sugar level was significantly correlated with log ferritin (p = 0.034). These results suggest that serum ferritin can be employed as a marker of not only glucose homeostasis but also insulin resistance both in type 2 diabetic and control subjects.
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PMID:Serum ferritin in healthy subjects and type 2 diabetic patients. 1095 94

The zinc content in the pancreatic beta cell is among the highest of the body, but information about which proteins might handle zinc in the beta cell is unknown. In the present work RT-PCR was used to obtain clues about the developmental expression of genes encoding metal complexing proteins in the pancreatic islets of the normal Sprague-Dawley rat and the BB diabetes resistant (BBDR) rat. The BBDR rat possesses beta cells genetically identical to the BB diabetes prone (BBDP) rat which exhibits an autoimmune diabetes quite similar to type 1 diabetes in humans, but in contrast to the BBDP rat, the islets of the BBDR rat are amenable to study because they are not destroyed by immune attack. There was no difference in the expression of any of the genes studied between the two strains of rats. mRNAs encoding zinc transport proteins ZnT-1 and ZnT-4, as well as calreticulin, ferritin heavy and light chains, metallothionein 1, metallothionein 3, Nramp1, Nramp2, transferrin, and the transferrin receptor were readily detected in pancreatic islets of 10-day-old, 5-week-old, and adult (60 to 90-day-old) rats. In contrast to the islet, mRNAs encoding metallothionein 3, Nramp1, Nramp2, ZnT-2, ZnT-3, and ZnT-4 and transferrin were not detected in the whole pancreas of adult Sprague-Dawley rats. In the whole pancreas of 3-day-old rats, ZnT-1 was the only zinc transporter mRNA detected and its level was moderate. Moderate to high levels of mRNA encoding calreticulin and the light and heavy chains of ferritin, as well as transferrin and the transferrin receptor, were detected in whole pancreas at 3 days. ZnT-2 and ZnT-3 mRNAs were present in low to moderate levels in pancreatic islets of 10-day and 5-week-old rats, but were absent in 3-day-old pancreas and islets of adult animals. These results indicate that expression of these proteins is developmentally regulated in the islet. In both Sprague-Dawley and BB rats, high levels of mRNAs encoding known beta cell proteins as controls (cytochrome b558, quinone reductase, the tricarboxylic acid transport protein and the receptors for IGF-1 and IGF-2 and insulin) were present in islets from 10 days to adulthood. Levels of mRNAs encoding quinone reductase, the tricarboxylic acid transport protein cytochrome b558 and the receptors for IGF-2 and insulin, were low or absent in 3-day-old and adult pancreas. BB rats were studied in an attempt to discern a difference between normal rats and the BB strain of rats, because, perhaps, delayed expression of a beta cell protein results in failure of immune tolerance against the beta cell. According to this paradigm none of the proteins examined in the current study appear to be a candidate for initiating an immune response in the BB rat.
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PMID:Survey of mRNAs encoding zinc transporters and other metal complexing proteins in pancreatic islets of rats from birth to adulthood: similar patterns in the Sprague-Dawley and Wistar BB strains. 1096 17

The role of iron-dependent oxidative metabolism in protecting the oxidable substrates contained in mature adipocytes is still unclear. Because differentiation increases ferritin formation in several cell types, thereby leading to an accumulation of H-rich isoferritins, we investigated whether differentiation affects iron metabolism in 3T3-L1 pre-adipocytes. To this aim, we evaluated the expression of the genes coding for the H and L ferritin subunits and for cytoplasmic iron regulatory protein (IRP) during the differentiation of 3T3-L1 cells in adipocytes induced by the addition of isobutylmethylxanthine, insulin, and dexamethasone. Differentiation enhanced ferritin formation and caused overexpression of the H subunit, thus altering the H/L subunit ratio. Northern blot analysis showed increased levels of H subunit mRNA. A gel retardation assay of cytoplasmic extract from differentiated cells, using an iron-responsive element as a probe, revealed enhanced an RNA binding capacity of IRP1, which correlated with the increase of IRP1 mRNA. The observed correlation between differentiation and iron metabolism in adipocytes suggests that an accumulation of H-rich isoferritin may limit the toxicity of iron in adipose tissue, thus exerting an antioxidant function.
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PMID:Overexpression of H ferritin and up-regulation of iron regulatory protein genes during differentiation of 3T3-L1 pre-adipocytes. 1097 28

The paradox of hematocrit in exercise physiology is that artificially increasing it by autotransfusion or erythropoietin doping improves VO2 max and performance, while in normal conditions there is a strong negative correlation between hematocrit and fitness, due to a training-induced "autohemodilution". We aimed at investigating: (a) which is the physiological range of hematocrit in highly trained professional footballers; (b) what are the characteristics of athletes with high vs low hematocrit? We determined in 77 healthy male footballers the physiological range (mean +/- sd) of hematocrit: 42.3+/-2.74, (range -2sigma/+2sigma = 36.8-47.8%) thus defining boundaries of quintiles of distribution for this parameter: 40, 41.6, 42.9, 44.6. In another sample of 42 male footballers we compared three groups: lowest quintile (n = 8), highest quintile (n = 5) and the three middle quintiles considered together (n = 29). Athletes in the lowest quintile compared to those in the four other quintiles had a lower value of blood viscosity (-8%, p < 0.01) but this difference disappeared after correction for hematocrit. These subjects with low hematocrit had also higher values of the following parameters: aerobic working capacity (p < 0.01); isometric adductor strength (p = 0.02); crossover point of carbohydrate oxidation (70% carbohydrates/30% lipids) (p < 0.05); insulin like growth factor binding protein 1 (p < 0.0001). Athletes in the highest quintile had higher red cell aggregability (Myrenne index "M1" 8.45+/-0.38 vs 6.82+/-0.62, p < 0.04) and a higher disaggregability threshold gammaD (72.6+/-22.63 vs 44.49+/-1.37, p < 0.01) and a lower percentage of water in fat-free mass (p < 0.02). On the whole sample hematocrit was negatively correlated with aerobic working capacity (W170 r = -0.329, p = 0.007; Wmax (% of expected value) r = -0.552, p = 0.008; VO2 max (% of expected value) r = -0.543, p = 0.009) and with ferritin (r = -0.33, p = 0.031), and positively correlated with the overtraining score (r = 0.352, p = 0.019) which was in turn negatively correlated with ferritin r = -0.312, p = 0.02). Besides, hematocrit behaves as a major determinant of blood viscosity (correlation with blood viscosity r = 0.997, p < 10(-7)) and erythrocyte disaggregability gammaD (r = 0.384, p = 0.03), but the hematocrit/viscosity ratio (h/eta index of O2 delivery) remains maintained almost constant over the range of values studied. These results show that (a) physiological values of hematocrit in these athletes are comprised between 36 and 48%; (b) "low" hematocrit (<40%) was associated with a higher aerobic capacity; (c) subjects with the higher hematocrits (>44.6%) were frequently overtrained and/or iron-deficient, and their blood viscosity (and red cell disaggregability) tended to be increased.
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PMID:The paradox of hematocrit in exercise physiology: which is the "normal" range from an hemorheologist's viewpoint? 1108 66


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