Ferritin Levels and Their Association With Regional Brain Volumes in Tourette's Syndrome

PubMed Central

Gorman, Daniel A.; Zhu, Hongtu; Anderson, George M.; Davies, Mark; Peterson, Bradley S.

2008-01-01

Objective A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes. Method Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter. Results Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices. Conclusions The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics. PMID:16816233

Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

PubMed

Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

2015-09-01

The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=<0.001), glucose (p=<0.001), insulin (p=<0.001) and HOMA IR score (p=<0.0001) in cases of metabolic syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

Ferritin Levels in Colombian Children: Findings from the 2010 National Nutrition Survey (ENSIN).

PubMed

Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Martínez-Torres, Javier; González-Ruíz, Katherine; Lobelo, Felipe

2016-04-05

Low ferritin is associated with many adverse health outcomes and is highly prevalent worldwide. The aim of this study was to describe the key findings related to plasma ferritin levels to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. We analyzed cross-sectional data from 6650 Colombian children between the ages of 5 and 12. Plasma ferritin levels were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. All analyses were conducted considering the complex nature of the sample. Of the children assessed, 3.5% had low ferritin, defined as levels <12 µg/L. A multivariate logistic regression analysis revealed increased risks for low ferritin levels among black or Afro-Colombian ethnic group and for those living in the northern, western and southern regions of the country. In conclusion, a significant prevalence of anemia caused by low ferritin levels was found and various sociodemographic factors were associated with this finding in Colombia. Continued surveillance and implementation of interventions to improve dietary patterns among the identified high-risk groups should be considered. Implementing these recommendations can help reduce manifestations of iron deficiency (e.g., delays in infant and child development) and thus improve public health.

Ferritin Levels in Colombian Children: Findings from the 2010 National Nutrition Survey (ENSIN)

PubMed Central

Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Martínez-Torres, Javier; González-Ruíz, Katherine; Lobelo, Felipe

2016-01-01

Low ferritin is associated with many adverse health outcomes and is highly prevalent worldwide. The aim of this study was to describe the key findings related to plasma ferritin levels to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. We analyzed cross-sectional data from 6650 Colombian children between the ages of 5 and 12. Plasma ferritin levels were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. All analyses were conducted considering the complex nature of the sample. Of the children assessed, 3.5% had low ferritin, defined as levels <12 µg/L. A multivariate logistic regression analysis revealed increased risks for low ferritin levels among black or Afro-Colombian ethnic group and for those living in the northern, western and southern regions of the country. In conclusion, a significant prevalence of anemia caused by low ferritin levels was found and various sociodemographic factors were associated with this finding in Colombia. Continued surveillance and implementation of interventions to improve dietary patterns among the identified high-risk groups should be considered. Implementing these recommendations can help reduce manifestations of iron deficiency (e.g., delays in infant and child development) and thus improve public health. PMID:27058547

Increased serum ferritin levels are independently related to incidence of prediabetes in adult populations.

PubMed

Meng, G; Yang, H; Bao, X; Zhang, Q; Liu, L; Wu, H; Du, H; Xia, Y; Shi, H; Guo, X; Liu, X; Li, C; Su, Q; Gu, Y; Fang, L; Yu, F; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Wu, Y; Niu, K

2017-04-01

To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. This prospective cohort study (n=7380) with a mean follow-up of 3.07 years (range: 1-7, 95% CI: 3.03-3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90-1.40), 1.20 (0.97-1.48), 1.41 (1.14-1.73) and 1.73 (1.41-2.11); and for women, 1.00, 1.01 (0.74-1.38), 0.68 (0.48-0.96), 0.84 (0.61-1.15) and 1.07 (0.80-1.45), respectively. Similar results were also observed for mean ferritin levels. Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels. Copyright © 2016. Published by Elsevier Masson SAS.

Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity.

PubMed

Andrews, Mónica; Soto, Néstor; Arredondo-Olguín, Miguel

2015-01-01

The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P < 0.006). Multiple linear regression analysis showed an association between diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

Soybean Ferritin Expression in Saccharomyces cerevisiae Modulates Iron Accumulation and Resistance to Elevated Iron Concentrations

PubMed Central

de Llanos, Rosa; Martínez-Garay, Carlos Andrés; Fita-Torró, Josep; Romero, Antonia María; Martínez-Pastor, María Teresa

2016-01-01

ABSTRACT Fungi, including the yeast Saccharomyces cerevisiae, lack ferritin and use vacuoles as iron storage organelles. This work explored how plant ferritin expression influenced baker's yeast iron metabolism. Soybean seed ferritin H1 (SFerH1) and SFerH2 genes were cloned and expressed in yeast cells. Both soybean ferritins assembled as multimeric complexes, which bound yeast intracellular iron in vivo and, consequently, induced the activation of the genes expressed during iron scarcity. Soybean ferritin protected yeast cells that lacked the Ccc1 vacuolar iron detoxification transporter from toxic iron levels by reducing cellular oxidation, thus allowing growth at high iron concentrations. Interestingly, when simultaneously expressed in ccc1Δ cells, SFerH1 and SFerH2 assembled as heteropolymers, which further increased iron resistance and reduced the oxidative stress produced by excess iron compared to ferritin homopolymer complexes. Finally, soybean ferritin expression led to increased iron accumulation in both wild-type and ccc1Δ yeast cells at certain environmental iron concentrations. IMPORTANCE Iron deficiency is a worldwide nutritional disorder to which women and children are especially vulnerable. A common strategy to combat iron deficiency consists of dietary supplementation with inorganic iron salts, whose bioavailability is very low. Iron-enriched yeasts and cereals are alternative strategies to diminish iron deficiency. Animals and plants possess large ferritin complexes that accumulate, detoxify, or buffer excess cellular iron. However, the yeast Saccharomyces cerevisiae lacks ferritin and uses vacuoles as iron storage organelles. Here, we explored how soybean ferritin expression influenced yeast iron metabolism, confirming that yeasts that express soybean seed ferritin could be explored as a novel strategy to increase dietary iron absorption. PMID:26969708

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

PubMed

Coelho-Borges, Silvia; Cheinquer, Hugo; Wolff, Fernando Herz; Cheinquer, Nelson; Krug, Luciano; Ashton-Prolla, Patricia

2012-01-01

Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Rate of Decline of Ferritin in Patients with Hemophagocytic Lymphohistiocytosis as a Prognostic Variable for Mortality

PubMed Central

Lin, Tiffany F.; Ferlic-Stark, Laura L.; Allen, Carl E.; Kozinetz, Claudia A.; McClain, Kenneth L.

2012-01-01

Hemophagocytic lymphohistiocytosis (HLH) is difficult to diagnose and treat. Highly elevated ferritin is strongly associated with HLH and levels may provide a prognostic marker. A comprehensive review of ferritin data from our patients during treatment was analyzed with respect to mortality. A patient was 17 times more likely to die when percent ferritin decrease was less than 50% as compared to a 96% or greater decrease as indicated with multivariate logistic modeling. Higher maximum ferritin levels in the first 3 weeks also contributed to the odds of death (OR=5.6;90%CI=1.2-24.9). Regular ferritin measurements may be useful predicting outcomes in HLH patients. PMID:20842751

Ferritin and iron levels in children with autistic disorder.

PubMed

Hergüner, Sabri; Keleşoğlu, Fatih Mehmet; Tanıdır, Cansaran; Cöpür, Mazlum

2012-01-01

Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.

Relationship between serum ferritin levels and sarcopenia in Korean females aged 60 years and older using the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3), 2008-2009.

PubMed

Kim, Tae Ho; Hwang, Hee-Jin; Kim, Sang-Hwan

2014-01-01

It has been suggested that elevated serum ferritin is associated with several metabolic disorders. However, there is no reported study assessing any association between serum ferritin and sarcopenia despite the close relationship between sarcopenia and metabolic disorders. We investigated whether serum ferritin was associated with sarcopenia in older Koreans. We conducted a cross-sectional study based on data acquired in the second and third years (2008-9) of the fourth Korean National Health and Nutrition Examination Survey. In total, 952 men (mean age 69.0 years) and 1,380 women (mean age 69.3 years) aged 60 years and older completed a body composition study using dual energy X-ray absorptiometry. Serum ferritin levels were measured. Sarcopenia was defined as an appendicular skeletal mass as a percentage of body weight that was less than two standard deviations below the gender-specific mean for young adults. Serum ferritin levels were lower in women than in men. Women with sarcopenia showed a higher level of serum ferritin than women without sarcopenia (men: without sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL). The prevalence of sarcopenia increased as the tertile of serum ferritin increased. However, statistical significance was only seen in elderly women (1(st) tertile 6.3%, 2(nd) tertile 8.0%, 3(rd) tertile 12.0%; p = 0.008). Without adjustment, compared with those in the lowest tertile of serum ferritin level, participants in the highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26-3.23) for sarcopenia in women. After adjusting for known risk factors, the OR for sarcopenia was 1.74 (95% CI = 1.02-2.97) in women. There was no statistically significant association between sarcopenia and serum ferritin tertiles in men. Elevated serum ferritin levels were associated with an increased prevalence of sarcopenia in women but not in men from a representative sample

Postmenopausal vegetarians' low serum ferritin level may reduce the risk for metabolic syndrome.

PubMed

Kim, Mi-Hyun; Bae, Yun Jung

2012-10-01

The present study was conducted to compare the serum ferritin status between the postmenopausal vegetarians and non-vegetarians and to identify the relation of serum ferritin with metabolic syndrome (MetS) risk factors in postmenopausal women. The two study groups consisted of postmenopausal vegetarians (n=59) who maintained a vegetarian diet for over 20 years and age-matched non-vegetarian controls (n=48). Anthropometric measurements, dietary intakes, serum metabolic syndrome-related parameters, and serum ferritin level between the two groups were compared. The vegetarians exhibited significantly lower weight (p<0.01), body mass index (BMI) (p<0.001), percentage of body fat (p<0.001), waist circumference (p<0.01), SBP (p<0.001), DBP (p<0.001), and fasting glucose (p<0.05). According to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III criteria for MetS applying Korean guidelines for waist circumference, the prevalence of MetS was lower in vegetarians (33.9 %) than in non-vegetarians (47.9 %). Vegetarians had significantly lower serum level of ferritin (p<0.01) than non-vegetarians. In the correlation analysis, serum ferritin was positively related to fasting glucose (r=0.264, p<0.01), triglycerides (r=0.232, p<0.05), and the NCEP score (r=0.214, p<0.05) and negatively related to high-density lipoprotein-cholesterol (r=-0.225, p<0.05) after adjusting for BMI, lifestyle, and dietary factors (animal protein, animal fat, and dietary fiber intake). In conclusion, postmenopausal vegetarians had lower MetS presence and a lower serum ferritin level compared to non-vegetarians. Furthermore, vegetarians' low serum ferritin level may reduce the risk of MetS in postmenopausal women.

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents

PubMed Central

Jung, Dong-Wook; Park, Joo-Hyun; Kim, Do-Hoon; Choi, Moonyoung; Kim, Shinhye; Kim, Hyonchong; Seul, Da-eun; Park, Soo Gyeong; Jung, Jin-Hyung; Han, Kyungdo; Park, Young-Gyu

2017-01-01

Abstract It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents. This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined. In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls. This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys. PMID:29390554

Evaluation and association of serum iron and ferritin levels in children with dental caries.

PubMed

Venkatesh Babu, N S; Bhanushali, Parin Vasant

2017-01-01

Iron deficiency anemia accounts for 90% of all types of anemia in the world. Although the prevalence has declined in recent years, it remains an important pediatric public health problem. Iron deficiency has also been associated with dental caries. It impairs salivary gland function causing reduced salivary secretion and buffering capacity leading to increased caries activity. The aim of the study is to explore an association between dental caries and serum levels of iron and ferritin in children aged 3-12 years. Subjectsand Methods: The study group included 120 children, hospitalized for uncomplicated medical problems. Blood reports were evaluated to determine serum iron and ferritin levels. Dental caries experience was assessed using deft index. The collected data were tabulated and analyzed using Student's t-test and Pearson's correlation coefficient. Out of 120 children, 38 children showed low serum iron levels of which 31 children had dental caries and nine out of 15 children in the high serum iron level group showed dental caries. High ferritin levels were seen in three children among which two children were caries-free and only one child had a low ferritin level who also had a positive deft score. Based on the results, it was concluded that there is an inverse association between serum iron levels and dental caries whereas there is no association between serum ferritin levels and dental caries.

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African-Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

PubMed Central

Rivers, Charles A.; Barton, James C.; Gordeuk, Victor R.; Acton, Ronald T.; Speechley, Mark R.; Snively, Beverly M.; Leiendecker-Foster, Catherine; Press, Richard D.; Adams, Paul C.; McLaren, Gordon D.; Dawkins, Fitzroy W.; McLaren, Christine E.; Reboussin, David M.

2007-01-01

The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (≥300 μg/L in men and ≥200 μg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P = 0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P = 0.047); corresponding differences were not observed among women. This appeared to be unrelated to self-reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P = 0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. PMID:17276706

Relationship between Serum Ferritin Levels and Sarcopenia in Korean Females Aged 60 Years and Older Using the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3), 2008–2009

PubMed Central

Kim, Tae Ho; Hwang, Hee-Jin; Kim, Sang-Hwan

2014-01-01

Context It has been suggested that elevated serum ferritin is associated with several metabolic disorders. However, there is no reported study assessing any association between serum ferritin and sarcopenia despite the close relationship between sarcopenia and metabolic disorders. Objective We investigated whether serum ferritin was associated with sarcopenia in older Koreans. Design and Setting We conducted a cross-sectional study based on data acquired in the second and third years (2008–9) of the fourth Korean National Health and Nutrition Examination Survey. Participants In total, 952 men (mean age 69.0 years) and 1,380 women (mean age 69.3 years) aged 60 years and older completed a body composition study using dual energy X-ray absorptiometry. Measurements Serum ferritin levels were measured. Sarcopenia was defined as an appendicular skeletal mass as a percentage of body weight that was less than two standard deviations below the gender-specific mean for young adults. Results Serum ferritin levels were lower in women than in men. Women with sarcopenia showed a higher level of serum ferritin than women without sarcopenia (men: without sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL). The prevalence of sarcopenia increased as the tertile of serum ferritin increased. However, statistical significance was only seen in elderly women (1st tertile 6.3%, 2nd tertile 8.0%, 3rd tertile 12.0%; p = 0.008). Without adjustment, compared with those in the lowest tertile of serum ferritin level, participants in the highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26–3.23) for sarcopenia in women. After adjusting for known risk factors, the OR for sarcopenia was 1.74 (95% CI = 1.02–2.97) in women. There was no statistically significant association between sarcopenia and serum ferritin tertiles in men. Conclusions Elevated serum ferritin levels were associated

Clinical Significance of Serum Ferritin at Diagnosis in Patients With Acute Myeloid Leukemia: A YACHT Multicenter Retrospective Study.

PubMed

Tachibana, Takayoshi; Andou, Taiki; Tanaka, Masatsugu; Ito, Satomi; Miyazaki, Takuya; Ishii, Yoshimi; Ogusa, Eriko; Koharazawa, Hideyuki; Takahashi, Hiroyuki; Motohashi, Kenji; Aoki, Jun; Nakajima, Yuki; Matsumoto, Kenji; Hagihara, Maki; Hashimoto, Chizuko; Taguchi, Jun; Fujimaki, Katsumichi; Fujita, Hiroyuki; Fujisawa, Shin; Kanamori, Heiwa; Nakajima, Hideaki

2018-06-01

A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML). The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients. The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003). Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of Serum Ferritin and the Development of Metabolic Syndrome in Middle-Aged Korean Men

PubMed Central

Park, Sung Keun; Ryoo, Jae-Hong; Kim, Min-Gi; Shin, Ju-Young

2012-01-01

OBJECTIVE Elevated serum ferritin has been known to be associated with the prevalence of metabolic syndrome (MetS). However, there was no research to examine whether serum ferritin levels have been actually associated with the prospective development of MetS. Accordingly, we carried out a prospective study to evaluate the longitudinal effects of baseline serum ferritin levels on the development of MetS. RESEARCH DESIGN AND METHODS A MetS-free cohort of 18,022 healthy Korean men, who had participated in a medical health checkup program in 2005, was followed until 2010. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Cox proportional hazards models were performed. RESULTS During 45,919.3 person-years of follow-up, 2,127 incident cases of MetS developed between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% CI) for incident MetS comparing the second quintile to the fifth quintile of serum ferritin levels versus the first quintile were 1.19 (0.98–1.45), 1.17 (0.96–1.43), 1.36 (1.12–1.65), and 1.66 (1.38–2.01), respectively (P for trend <0.001). These associations were apparent in the clinically relevant subgroup analyses. CONCLUSIONS Elevated serum ferritin levels were independently associated with future development of MetS during the 5-year follow-up period. PMID:22933431

Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels.

PubMed

Wofford, Joshua D; Chakrabarti, Mrinmoy; Lindahl, Paul A

2017-03-31

Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from 57 Fe-enriched mice were evaluated by Mössbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood, whereas the other was due to [Fe 4 S 4 ] 2+ clusters and low-spin Fe II hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE -/- mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE -/- livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2 -/- hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the heart from the mother contained low ferritin and normal levels of mitochondrial iron. High-spin Fe II ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mössbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?

PubMed

Barut, Sener; Dincer, Fatma; Sahin, Idris; Ozyurt, Huseyin; Akkus, Mehmet; Erkorkmaz, Unal

2010-01-01

Serum ferritin is one of the markers indicating hemophagocytosis that may have a role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). This study was designed to determine any correlation between serum ferritin and routine diagnostic laboratory markers of CCHF, and to investigate the relationship between serum ferritin levels and disease severity. Sixty-six patients with CCHF admitted to the hospital during the spring and summer months of 2006 and 2007 were included in the study. Serum ferritin levels were measured in sera obtained during the initial days of hospitalization. Data from 53 patients showing decreasing platelet counts over the first three days were used for further analysis and these patients were divided into two groups according to disease severity: group A included severe cases with lowest platelet counts < or =20x10(9)/l and group B included mild cases with lowest platelet counts >20x10(9)/l. Forty patients (60.6%) were male (mean age 43+/-17 years). Three patients died, thus the fatality rate was 4.5%. Fifty-one patients (77.3%) had abnormal serum ferritin levels, with levels above 500 ng/ml in 62.1%. There was a significant negative correlation between ferritin levels and concordant platelet counts (p<0.001; r=-0.416) and ferritin was also found to be positively correlated with aspartate aminotransferase (p<0.001; r=0.625), alanine aminotransferase (p<0.001; r=0.479), and lactate dehydrogenase (p<0.001; r=0.684). Group A had higher ferritin levels than group B (p < 0.001). Receiver operating characteristic analysis revealed that a ferritin level of > or =1862ng/ml had a sensitivity of 87.5% and a specificity of 83.8% in differentiating severe cases from mild ones. Increased serum ferritin levels may suggest a significant role of hemophagocytosis in the pathogenesis of CCHF and may be a useful marker for diagnosis, disease activity, and prognosis. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd

Obese women less likely to have low serum ferritin, Nicaragua

PubMed Central

Wendt, Amanda S; Jefferds, Maria E; Perrine, Cria G; Halleslevens, Patricia; Sullivan, Kevin M

2015-01-01

Objective To examine the association between overweight and obesity and serum ferritin among women of reproductive age (15–49 years) in Nicaragua, considering the effect of α1-acid glycoprotein (AGP), a marker of inflammation. Design We analysed data from the 2004–05 Nicaraguan Integrated Surveillance System for Nutrition Interventions. Three logistic regression models were analysed with low serum ferritin (<15 μg/l) as the dependent variable: (i) overweight or obese status and covariates; (ii) model 1 plus AGP; and (iii) model 1 restricted to only women with normal AGP levels (≤1·0 g/l). Setting Nicaragua. Subjects Included in this analysis were 832 non-pregnant mother/caregivers (15–49 years) surveyed in 2004–2005. Results In the sample, prevalence of overweight and obesity was 31·8 % and 19·2 %, respectively, and 27·6 % had low serum ferritin. In model 1, the adjusted OR of low serum ferritin was 0·74 (95 % CI 0·52, 1·05) for overweight women and 0·42 (95 % CI 0·26, 0·65) for obese women. In model 2, AGP was significantly independently associated with low serum ferritin (adjusted OR=0·56, 95 % CI 0·34, 0·92) while the adjusted OR for overweight and obesity were largely unchanged. Excluding women with elevated AGP did not appreciably affect the relationship between overweight or obesity and low serum ferritin (model 3). Conclusions Overall, in this population of reproductive-age women, obese women were less likely to have low serum ferritin levels, and this was independent of inflammation as measured by AGP. PMID:24848519

DETERMINATION OF FERRITIN AND HEMOSIDERIN IRON IN PATIENTS WITH NORMAL IRON STORES AND IRON OVERLOAD BY SERUM FERRITIN KINETICS

PubMed Central

SAITO, HIROSHI; TOMITA, AKIHIRO; OHASHI, HARUHIKO; MAEDA, HIDEAKI; HAYASHI, HISAO; NAOE, TOMOKI

2012-01-01

ABSTRACT We attempted to clarify the storage iron metabolism from the change in the serum ferritin level. We assumed that the nonlinear decrease in serum ferritin was caused by serum ferritin increase in iron mobilization. Under this assumption, we determined both ferritin and hemosiderin iron levels by computer-assisted simulation of the row of decreasing assay-dots of serum ferritin in 11 patients with normal iron stores free of both iron deficiency and iron overload; chronic hepatitis C (CHC) and iron deficiency anemia after treatment, and 11 patients with iron overload; hereditary hemochromatosis (HH) and transfusion-dependent anemias (TD). We determined the iron removal rates of 20 and 17 mg/day by administering mean doses of deferasirox at 631 and 616 mg/day in 2 TD during the period of balance of iron addition and removal as indicated by the serum ferritin returned to the previous level. The ferritin-per-hemosiderin ratio was almost the same in both HH and CHC. This matched the localized hepatic hemosiderin deposition in CHC with normal iron stores. We detected the ferritin increased by utilizing the hemosiderin iron in iron removal and the ferritin reduced by transforming ferritin into hemosiderin in iron additions. The iron storing capacity of hemosiderin was limitless, while that of ferritin was suppressed when ferritin iron exceeded around 5 grams. We confirmed the pathway of iron from hemosiderin to ferritin in iron mobilization, and that from ferritin to hemosiderin in iron deposition. Thus, serum ferritin kinetics enabled us to be the first to clinically clarify storage iron metabolism. PMID:22515110

Siderosomal ferritin. The missing link between ferritin and haemosiderin?

PubMed Central

Andrews, S C; Treffry, A; Harrison, P M

1987-01-01

A minor electrophoretically fast component was found in ferritin from iron-loaded rat liver in addition to a major electrophoretically slow ferritin similar to that observed in control rats. The electrophoretically fast ferritin showed immunological identity with the slow component, but on electrophoresis in SDS it gave a peptide of 17.3 kDa, in contrast with the electrophoretically slow ferritin, which gave a major band corresponding to the L-subunit (20.7 kDa). Thus the electrophoretically fast ferritin resembles that reported by Massover [(1985) Biochim. Biophys. Acta 829, 377-386] in livers of mice with short-term parenteral iron overload. The electrophoretically fast ferritin had a lower iron content (2000 Fe atoms/molecule) than the electrophoretically slow ferritin (3000 Fe atoms/molecule). Removal and re-incorporation of iron was possible without effect on the electrophoretic mobility of either ferritin species. On subcellular fractionation the electrophoretically fast ferritin was enriched in pellet fractions and was the sole soluble ferritin isolated from iron-laden secondary lysosomes (siderosomes). The amount and relative proportion of the electrophoretically fast species increased with iron loading. Haemosiderin isolated from siderosomes was found to contain a peptide reactive to anti-ferritin serum and corresponding to the 17.3 kDa peptide of the electrophoretically fast ferritin species. Unlike the electrophoretically slow ferritin, the electrophoretically fast ferritin did not become significantly radioactive in a 1 h biosynthetic labelling experiment. We conclude that the minor ferritin is not, as has been suggested for mouse liver ferritin, 'a completely new species of smaller holoferritin that represents a shift in the ferritin phenotype' in response to siderosis, but a precursor of haemosiderin, in agreement with the proposal by Richter [(1984) Lab. Invest. 50, 26-35] concerning siderosomal ferritin. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. PMID

Elevated serum ferritin concentration is associated with incident type 2 diabetes mellitus in a Chinese population: A prospective cohort study.

PubMed

Chen, Ling; Li, Yufeng; Zhang, Fang; Zhang, Simin; Zhou, Xianghai; Ji, Linong

2018-05-01

We aimed to evaluate the association between serum ferritin levels and incident type 2 diabetes mellitus risk in a Chinese population. This cohort study assessed 2225 Chinese individuals aged 25-75 years. Diabetes mellitus was diagnosed using the 1999 World Health Organization definition with a median follow-up period of 20 months. Cox proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (CI) for incident diabetes when serum ferritin concentrations increased by one standard deviation. During the follow-up period, 112 cases (62 men and 50 women) of type 2 diabetes mellitus were identified. Baseline serum ferritin levels were higher in the diabetes than the non-diabetes group. After adjusting for age, body mass index, waist circumference, mean arterial pressure, fasting plasma glucose, fasting insulin, hemoglobin A1c, total cholesterol, high-density lipoprotein cholesterol, alanine transaminase and triglyceride levels, family history of diabetes mellitus, pork meat consumption, neutrophil/lymphocyte ratio, education, and annual household income, the hazard ratios for incident diabetes corresponding to one standard deviation increase in serum ferritin levels were 1.17 (95% CI 1.03, 1.34), 1.20 (95% CI 1.003, 1.43), and 1.03 (95% CI 0.82, 1.31) for the total population, men, and women, respectively. High serum ferritin levels were associated with a higher risk of incident type 2 diabetes mellitus independent of traditional risk factors in the total population and men. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship of serum ferritin level and tic severity in children with Tourette syndrome.

PubMed

Ghosh, Debabrata; Burkman, Elizabeth

2017-08-01

Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS. Children <18 years, diagnosed with TS during 2009-2015, were reviewed. Only those with serum ferritin testing were included. The following data were collected: tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up. In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron. Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

Nuclear ferritin: A new role for ferritin in cell biology.

PubMed

Alkhateeb, Ahmed A; Connor, James R

2010-08-01

Ferritin has been traditionally considered a cytoplasmic iron storage protein. However, several studies over the last two decades have reported the nuclear localization of ferritin, specifically H-ferritin, in developing neurons, hepatocytes, corneal epithelial cells, and some cancer cells. These observations encouraged a new perspective on ferritin beyond iron storage, such as a role in the regulation of iron accessibility to nuclear components, DNA protection from iron-induced oxidative damage, and transcriptional regulation. This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease. The nuclear translocation of ferritin is a selective energy-dependent process that does not seem to require a consensus nuclear localization signal. It is still unclear what regulates the nuclear import/export of ferritin. Some reports have implicated the phosphorylation and O-glycosylation of the ferritin protein in nuclear transport; others suggested the existence of a specific nuclear chaperone for ferritin. The data argue strongly for nuclear ferritin as a factor in human development and disease. Ferritin can bind and protect DNA from oxidative damage. It also has the potential of playing a regulatory role in transcription. Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule. Copyright 2010 Elsevier B.V. All rights reserved.

Ferritin accumulation under iron scarcity in Drosophila iron cells.

PubMed

Mehta, A; Deshpande, A; Bettedi, L; Missirlis, F

2009-10-01

Ferritins are highly stable, multi-subunit protein complexes with iron-binding capacities that reach 4500 iron atoms per ferritin molecule. The strict dependence of cellular physiology on an adequate supply of iron cofactors has likely been a key driving force in the evolution of ferritins as iron storage molecules. The insect intestine has long been known to contain cells that are responsive to dietary iron levels and a specialized group of "iron cells" that always accumulate iron-loaded ferritin, even when no supplementary iron is added to the diet. Here, we further characterize ferritin localization in Drosophila melanogaster larvae raised under iron-enriched and iron-depleted conditions. High dietary iron intake results in ferritin accumulation in the anterior midgut, but also in garland (wreath) cells and in pericardial cells, which together filter the circulating hemolymph. Ferritin is also abundant in the brain, where levels remain unaltered following dietary iron chelation, a treatment that depletes ferritin from the aforementioned tissues. We attribute the stability of ferritin levels in the brain to the function of the blood-brain barrier that may shield this organ from systemic iron fluctuations. Most intriguingly, our dietary manipulations demonstrably iron-depleted the iron cells without a concomitant reduction in their production of ferritin. Therefore, insect iron cells may constitute an exception from the evolutionary norm with respect to iron-dependent ferritin regulation. It will be of interest to decipher both the physiological purpose served and the mechanism employed to untie ferritin regulation from cellular iron levels in this cell type.

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study.

PubMed

Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev; Badmaev, Vladimir

2017-01-01

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis.

Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis.

PubMed

Thurnham, David I; McCabe, Linda D; Haldar, Sumanto; Wieringa, Frank T; Northrop-Clewes, Christine A; McCabe, George P

2010-09-01

The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated. The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations. We estimated the increase in ferritin associated with inflammation (ie, CRP gt 5 mg/L and/or AGP gt 1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only). In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P lt 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P lt 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ap 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID. Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups.

Characterization of mitochondrial ferritin in Drosophila.

PubMed

Missirlis, Fanis; Holmberg, Sara; Georgieva, Teodora; Dunkov, Boris C; Rouault, Tracey A; Law, John H

2006-04-11

Mitochondrial function depends on iron-containing enzymes and proteins, whose maturation requires available iron for biosynthesis of iron-sulfur clusters and heme. Little is known about how mitochondrial iron homeostasis is maintained, although the recent discovery of a mitochondrial ferritin in mammals and plants has uncovered a potential key player in the process. Here, we show that Drosophila melanogaster expresses mitochondrial ferritin from an intron-containing gene. It has high similarity to the mouse and human mitochondrial ferritin sequences and, as in mammals, is expressed mainly in testis. This ferritin contains a putative mitochondrial targeting sequence and an epitope-tagged version localizes to mitochondria in transfected cells. Overexpression of mitochondrial ferritin fails to alter both total-body iron levels and iron that is bound to secretory ferritins. However, the viability of iron-deficient flies is compromised by overexpression of mitochondrial ferritin, suggesting that it may sequester iron at the expense of other important cellular functions. The conservation of mitochondrial ferritin in an insect species underscores the importance of this iron-storage molecule.

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents: A nationwide population-based study.

PubMed

Jung, Dong-Wook; Park, Joo-Hyun; Kim, Do-Hoon; Choi, Moonyoung; Kim, Shinhye; Kim, Hyonchong; Seul, Da-Eun; Park, Soo Gyeong; Jung, Jin-Hyung; Han, Kyungdo; Park, Young-Gyu

2017-12-01

It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents.This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined.In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls.This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Ferritins and iron storage in plants.

PubMed

Briat, Jean-François; Duc, Céline; Ravet, Karl; Gaymard, Frédéric

2010-08-01

Iron is essential for both plant productivity and nutritional quality. Improving plant iron content was attempted through genetic engineering of plants overexpressing ferritins. However, both the roles of these proteins in the plant physiology, and the mechanisms involved in the regulation of their expression are largely unknown. Although the structure of ferritins is highly conserved between plants and animals, their cellular localization differ. Furthermore, regulation of ferritin gene expression in response to iron excess occurs at the transcriptional level in plants, in contrast to animals which regulate ferritin expression at the translational level. In this review, our knowledge of the specific features of plant ferritins is presented, at the level of their (i) structure/function relationships, (ii) cellular localization, and (iii) synthesis regulation during development and in response to various environmental cues. A special emphasis is given to their function in plant physiology, in particular concerning their respective roles in iron storage and in protection against oxidative stress. Indeed, the use of reverse genetics in Arabidopsis recently enabled to produce various knock-out ferritin mutants, revealing strong links between these proteins and protection against oxidative stress. In contrast, their putative iron storage function to furnish iron during various development processes is unlikely to be essential. Ferritins, by buffering iron, exert a fine tuning of the quantity of metal required for metabolic purposes, and help plants to cope with adverse situations, the deleterious effects of which would be amplified if no system had evolved to take care of free reactive iron. Copyright 2009 Elsevier B.V. All rights reserved.

Ferritin Blood Test: MedlinePlus Lab Test Information

MedlinePlus

... https://medlineplus.gov/labtests/ferritinbloodtest.html Ferritin Blood Test To use the sharing features on this page, please enable JavaScript. What is a Ferritin Blood Test? A ferritin blood test measures the level of ...

Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population

PubMed Central

Gordeuk, Victor R.; Reboussin, David M.; McLaren, Christine E.; Barton, James C.; Acton, Ronald T.; McLaren, Gordon D.; Harris, Emily L.; Reiss, Jacob A.; Adams, Paul C.; Speechley, Mark; Phatak, Pradyumna D.; Sholinsky, Phyliss; Eckfeldt, John H.; Chen, Wen-Pin; Passmore, Leah; Dawkins, Fitzroy W.

2013-01-01

How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 μg/L (men), >200 μg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but <4 g. In conclusion, serum ferritin >900 μg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 μg/L in male C282Y homozygotes is predictive of moderately increased iron stores. PMID:18429050

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.

PubMed

Kukulj, Suzana; Jaganjac, Morana; Boranic, Milivoj; Krizanac, Simun; Santic, Zarko; Poljak-Blazi, Marija

2010-06-01

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

Association of serum ferritin levels with immunological status and clinical staging of HIV patients: a retrospective study

NASA Astrophysics Data System (ADS)

Saragih, R. H.; Mardia, A. I.; Purba, G. C. F.; Syahrini, H.

2018-03-01

Serum ferritin has long known as an acute phase reactant during inflammation. It works as an oxidative stress marker beside its role in the storage of intracellular iron. The increase of serum ferritin levels (SFL) has been reported found in HIV patients. It remains unclear though whether it causes, or is the cause, to the progressivity of the disease. The purpose of this study was to find the association between the SFL and the progressivity of the HIV disease. A retrospective study of 91 patients was carried out at the Haji Adam Malik Central General Hospital. All of the study population were HIV positive inpatients admitted from January to December 2016. The data needed to be all obtained from the patient’s medical records. The WHO Clinical Staging System was used to assess the HIV clinical staging. An inverse relationship was found between the SFL with the immunological status of the HIV patients (r=-0.213) based on their CD4+ count. There was no association found between the SFL with the clinical staging of the HIV patients (p=0.953). The elevated SFL is a feature found in HIV-diagnosed patients with the low CD4+ count, and it affects the progressivity of the disease.

Lipid peroxidative damage in the erythrocytes and elevation of serum LDL-cholesterol, apolipoprotein-B, ferritin and uric acid with age and in coronary heart disease patients.

PubMed

El-Gebali, H H; Tahir, S A; Haider, S S; El-Fakhri, M M

2000-02-01

To determine the normal serum levels of LDL-cholesterol, apolipoprotein-B, ferritin, uric acid, and the extent of erythrocytes lipid peroxidation in healthy control group subjects and to compare them with coronary heart disease patients. Secondly, to study the effects of age and sex on these parameters. The blood samples from 150 healthy Libyan control group subjects (110 men and 40 women) were classified into 3 groups according to their age. Group I consisted of 76 subjects with an age range from 20 to 35 years. Group II consisted of 45 subjects with an age range from 36 to 50 years. Group III consisted of 29 subjects with an age range from 51 to 74 years. The blood samples from these groups were analyzed for LDL-cholesterol, apolipoprotein-B, ferritin and uric acid levels. Lipid peroxidation was compared in the erythrocytes of 56 selected healthy control group subjects (31 men and 11 women) of the aforementioned age groups. These parameters have shown age-dependent elevation in their levels. Meanwhile, LDL-cholesterol and Apolipoprotein-B levels in female subjects were higher than those of males. However, lipid peroxidation in the erythrocytes has revealed a statistically significant increase with increasing age. The comparison between 93 selected, sex and age matched, healthy control group subjects with 87 selected coronary heart disease patients (55 men and 45 women) with an age range from 30 to 74 years (49.6+13.25) has demonstrated significantly higher concentration of LDL-cholesterol, Apolipoprotein-B, ferritin and uric acid in coronary heart disease patients than those of healthy control group subjects. Meanwhile, lipid peroxidation was also significantly enhanced in coronary heart disease patients compared with healthy control group subjects. Our study has revealed that an increase in the lipid peroxidation in erythrocytes with age and during coronary heart disease, makes red cell membranes more vulnerable to free radical damage via formation of reactive

Mathematical modeling of the dynamic storage of iron in ferritin

PubMed Central

2010-01-01

Background Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Results Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. Conclusions The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress

Mathematical modeling of the dynamic storage of iron in ferritin.

PubMed

Salgado, J Cristian; Olivera-Nappa, Alvaro; Gerdtzen, Ziomara P; Tapia, Victoria; Theil, Elizabeth C; Conca, Carlos; Nuñez, Marco T

2010-11-03

Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1–Risk Myelodysplastic Syndrome—A Small, Investigative Study

PubMed Central

Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev; Badmaev, Vladimir

2017-01-01

Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. Aim: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Method: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. Results: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. Discussion: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis. PMID:29147080

Relationship between high serum ferritin level and glaucoma in a South Korean population: the Kangbuk Samsung health study.

PubMed

Gye, Hyo Jung; Kim, Joon Mo; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Sung, Ki Chul; Lee, Mi Yeon; Park, Ki Ho

2016-12-01

To investigate the association between serum ferritin levels and glaucoma in a South Korean population. This retrospective cross-sectional study included 164 029 subjects who underwent screening at Kangbuk Samsung Hospital Health Screening Center between August 2012 and July 2013. All subjects underwent a physical examination, answered sociodemographic and behavioural questions, and provided samples for laboratory analyses. A digital fundus photograph of both eyes was taken, and all photographs were reviewed by ophthalmologists. The ophthalmologists determined if an eye had glaucoma based on criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and the appearance of the retinal nerve fibre layer and optic disc. The mean serum ferritin level was 56.98 ng/mL in women and 223.82 ng/mL in men. After adjusting for age, serum iron, total iron-binding capacity (TIBC), transferrin saturation, white blood cell (WBC) count, high-sensitivity C-reactive protein (HsCRP) and total vitamin D level, males in the highest quartile for serum ferritin level had a higher OR for glaucoma than males in the lowest quartile (OR=1.176, 95% CI 1.030 to 1.342, p=0.016); we did not observe this relationship among women. Other markers of iron metabolism, such as iron level, transferrin saturation and TIBC, and inflammation measures, including WBC, HsCRP and total vitamin D, were not associated with glaucoma. High serum ferritin level was associated with a high risk of glaucoma in men, but not in women. Because serum ferritin is related to oxidative stress and inflammation, it might play a role in glaucoma development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Relationship of Iron Deficiency and Serum Ferritin Levels with Pulmonary Hypertension: The Jackson Heart Study.

PubMed

Jankowich, Matthew; Elston, Beth; Evans, Samuel K; Wu, Wen-Chih; Choudhary, Gaurav

2016-01-01

Iron deficiency is prevalent in idiopathic pulmonary arterial hypertension (IPAH), but whether iron deficiency or ferritin levels are associated with pulmonary hypertension (PH) in the general population is unknown. We performed a cross-sectional analysis of data on iron deficiency (exposure), and PH (pulmonary artery systolic pressure>40mmHg on echocardiogram) (outcome) on subjects with complete data on exposures and outcomes as well as covariates (n = 2,800) enrolled in the Jackson Heart Study, a longitudinal prospective observational cohort study of heart disease in African-Americans from Jackson, Mississippi. Iron deficiency was defined as a serum ferritin level < 15ng/mL (females); < 30ng/mL (males). We determined crude prevalence ratios (PRs) for PH in iron deficient versus non-iron deficient groups using modified Poisson regression modeling. We also analyzed the prevalence of PH by sex-specific quartiles of ferritin (Females ≤ 47ng/mL; > 47ng/mL- 95ng/mL; > 95ng/mL- 171ng/mL; > 171ng/mL; Males ≤ 110ng/mL; > 110ng/mL- 182ng/mL; > 182ng/mL- 294ng/mL; > 294ng/mL), using the same modeling technique with the lowest quartile as the referent. Median pulmonary artery systolic pressure was 27mmHg (interquartile range 23-31mmHg) in the study cohort. 147 subjects (5.2%) had PH and 140 (5.0%) had iron deficiency. However, of the 147 subjects with PH, only 4 were also iron deficient. The crude PH PR was 0.5 (95% CI 0.2-1.4) in iron-deficiency compared to non-deficient. In analysis by quartiles of ferritin, adjusting for age and sex, there was no evidence of association with PH in quartiles 2 (PR 1.1, 95% CI 0.7-1.6), 3 (PR 0.8, 95% CI 0.5-1.3), or 4 (PR 0.8, 95% CI 0.5-1.2) compared with quartile 1 (referent group, PR 1). Further analyses of the relationship between PH and ferritin as a log-transformed continuous variable or by quartiles of serum iron showed similar results. In the Jackson Heart Study, the prevalence of PH was similar in iron-deficient and non

Circulating ferritin concentrations and risk of type 2 diabetes in Japanese individuals.

PubMed

Akter, Shamima; Nanri, Akiko; Kuwahara, Keisuke; Matsushita, Yumi; Nakagawa, Tohru; Konishi, Maki; Honda, Toru; Yamamoto, Shuichiro; Hayashi, Takeshi; Noda, Mitsuhiko; Mizoue, Tetsuya

2017-07-01

Higher iron storage has been linked to an increased risk of type 2 diabetes, but little is known about the mediator of this association. Here, we prospectively investigated the association between circulating ferritin, a marker of iron storage, and the incidence of type 2 diabetes among Japanese individuals. The participants were 4,754 employees who attended a comprehensive health check-up in 2008-2009 and donated blood for the study. During 5 years of follow up, diabetes was identified based on plasma glucose, glycated hemoglobin and self-report. Two controls matched to each case on sex, age and date of check-up were randomly chosen using density sampling, giving 327 cases and 641 controls with ferritin measurement. Cox proportional hazards regression was used to estimate the hazard ratio while adjusting for a series of potential confounders or mediators. Elevated serum ferritin levels were associated with a significantly increased risk of type 2 diabetes, with the hazard ratio adjusted for known risk factors in the highest vs lowest quartile of 1.42 (95% confidence interval: 1.03-1.96). This association was unchanged after adjustment for C-reactive protein and adiponectin, but attenuated after adjustment for liver enzyme and insulin resistance (hazard ratio 1.04). The ferritin-diabetes association was confined to non-obese participants. These results suggest that elevated iron storage is associated with increased risk of type 2 diabetes in normal weight individuals, and that this association is partly mediated through liver dysfunction and resulting insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Sequence analysis of dolphin ferritin H and L subunits and possible iron-dependent translational control of dolphin ferritin gene

PubMed Central

Takaesu, Azusa; Watanabe, Kiyotaka; Takai, Shinji; Sasaki, Yukako; Orino, Koichi

2008-01-01

Background Iron-storage protein, ferritin plays a central role in iron metabolism. Ferritin has dual function to store iron and segregate iron for protection of iron-catalyzed reactive oxygen species. Tissue ferritin is composed of two kinds of subunits (H: heavy chain or heart-type subunit; L: light chain or liver-type subunit). Ferritin gene expression is controlled at translational level in iron-dependent manner or at transcriptional level in iron-independent manner. However, sequencing analysis of marine mammalian ferritin subunits has not yet been performed fully. The purpose of this study is to reveal cDNA-derived amino acid sequences of cetacean ferritin H and L subunits, and demonstrate the possibility of expression of these subunits, especially H subunit, by iron. Methods Sequence analyses of cetacean ferritin H and L subunits were performed by direct sequencing of polymerase chain reaction (PCR) fragments from cDNAs generated via reverse transcription-PCR of leukocyte total RNA prepared from blood samples of six different dolphin species (Pseudorca crassidens, Lagenorhynchus obliquidens, Grampus griseus, Globicephala macrorhynchus, Tursiops truncatus, and Delphinapterus leucas). The putative iron-responsive element sequence in the 5'-untranslated region of the six different dolphin species was revealed by direct sequencing of PCR fragments obtained using leukocyte genomic DNA. Results Dolphin H and L subunits consist of 182 and 174 amino acids, respectively, and amino acid sequence identities of ferritin subunits among these dolphins are highly conserved (H: 99–100%, (99→98) ; L: 98–100%). The conserved 28 bp IRE sequence was located -144 bp upstream from the initiation codon in the six different dolphin species. Conclusion These results indicate that six different dolphin species have conserved ferritin sequences, and suggest that these genes are iron-dependently expressed. PMID:18954429

Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still's disease: A multicenter retrospective study.

PubMed

Kirino, Yohei; Kawaguchi, Yasushi; Tada, Yoshifumi; Tsukamoto, Hiroshi; Ota, Toshiyuki; Iwamoto, Masahiro; Takahashi, Hiroki; Nagasawa, Kohei; Takei, Shuji; Horiuchi, Takahiko; Ichida, Hisae; Minota, Seiji; Ueda, Atsuhisa; Ohta, Akihide; Ishigatsubo, Yoshiaki

2018-01-11

Heme oxygenase (HO)-1 is a heme-degrading enzyme highly expressed in monocyte/macrophage, serum levels of which may be promising biomarker for adult-onset Still's disease (AOSD). We here report data on the use of serum ferritin and HO-1 levels in AOSD. Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD patients. Three independent experts judged whether the patients were definite AOSD depending on the clinical information. These 91 'definite AOSD' patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. Serum ferritin and HO-1 levels were measured using ELISA. Associations between clinical symptoms, serum ferritin, and HO-1 were explored. Multivariate regression analysis was performed to identify independent variables associated with definite AOSD diagnosis. Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia. Receiver operating characteristic analysis identified optimal levels of serum ferritin (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p = .013), suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status. Multivariate analysis identified neutrophilia, RF/ANA negativity, sore throat, and elevated serum HO-1 as independent variables associated with AOSD diagnosis. We confirmed that serum ferritin and HO-1 serve as highly specific and sensitive

Controlled Aggregation of Ferritin to Modulate MRI Relaxivity

PubMed Central

Bennett, Kevin M.; Shapiro, Erik M.; Sotak, Christopher H.; Koretsky, Alan P.

2008-01-01

Ferritin is an iron storage protein expressed in varying concentrations in mammalian cells. The deposition of ferric iron in the core of ferritin makes it a magnetic resonance imaging contrast agent, and ferritin has recently been proposed as a gene expression reporter protein for magnetic resonance imaging. To date, ferritin has been overexpressed in vivo and has been coexpressed with transferrin receptor to increase iron loading in cells. However, ferritin has a relatively low T2 relaxivity (R2 ≈ 1 mM−1s−1) at typical magnetic field strengths and so requires high levels of expression to be detected. One way to modulate the transverse relaxivity of a superparamagnetic agent is to cause it to aggregate, thereby manipulating the magnetic field gradients through which water diffuses. In this work, it is demonstrated by computer simulation and in vitro that aggregation of ferritin can alter relaxivity. The effects of aggregate size and intraaggregate perturber spacing on R2 are studied. Computer modeling indicates that the optimal spacing of the ferritin molecules in aggregate for increasing R2 is 100–200 nm for a typical range of water diffusion rates. Chemical cross-linking of ferritin at 12 Å spacing led to a 70% increase in R2 compared to uncross-linked ferritin controls. To modulate ferritin aggregation in a potentially biologically relevant manner, ferritin was attached to actin and polymerized in vitro. The polymerization of ferritin-F-actin caused a 20% increase in R2 compared to unpolymerized ferritin-G-actin. The R2-value was increased by another 10% by spacing the ferritin farther apart on the actin filaments. The modulation of ferritin aggregation by binding to cytoskeletal elements may be a useful strategy to make a functional reporter gene for magnetic resonance imaging. PMID:18326661

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing.

PubMed

Karaboyas, Angelo; Zee, Jarcy; Morgenstern, Hal; Nolen, Jacqueline G; Hakim, Raymond; Kalantar-Zadeh, Kamyar; Zager, Philip; Pisoni, Ronald L; Port, Friedrich K; Robinson, Bruce M

2015-10-07

Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time. Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation. Copyright © 2015 by

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing

PubMed Central

Zee, Jarcy; Morgenstern, Hal; Nolen, Jacqueline G.; Hakim, Raymond; Kalantar-Zadeh, Kamyar; Zager, Philip; Pisoni, Ronald L.; Port, Friedrich K.; Robinson, Bruce M.

2015-01-01

Background and objectives Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Design, setting, participants, & measurements Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients’ changes in ferritin over time. Results Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009–2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. Conclusions In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of

Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.

PubMed

Depalma, Ralph G; Hayes, Virginia W; Chow, Bruce K; Shamayeva, Galina; May, Patricia E; Zacharski, Leo R

2010-06-01

This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death. Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with

Soluble transferrin receptor, Ferritin index in Pakistani population.

PubMed

Alam, Faiza; Ashraf, Nabeel; Kashif, Ramsha; Arshad, Hashaam; Fatima, Syeda Sadia

2017-03-01

Inflammation affects the reliability of ferritin. The serum level of transferrin receptor protein (sTfR) represents true demand of iron in the body. This study attempts to identify levels of sTfR and correlate the trends of sTfR/ferritin index with BMI in the population of Karachi. 132 gender matched volunteers between the ages of 20-60 years were recruited for this cross-sectional study. BMI was calculated using the formula: (weight in kg / height in m2). Following groups were made according to South Asian criteria of BMI; Group A: normal weight (18.0-22.9 kg/m 2 ), Group B: overweight (23.0-24.9 kg/m2), Group C: obese (>25.0 kg/m 2 ). Serum ferritin, sTfR and CRP levels were determined using ELISA kits. Statistical comparisons were performed using Mann Whitney U and Spearman's rank correlation, where p<0.05 was considered significant. The results identified increased in TIBC, sTfR, ferritin and CRP in obese as compared to normal weight individuals (p<0.001). sTfR/ferritin ratio was 0.822 which signifies increased risk of acute myocardial infarction in group C. Serum iron (r=-0.359,p=0.004) showed negative correlation with BMI while serum ferritin (r=0.237,p< 0.001) and sTfR (r=0.263,p= 0.036) levels were positively associated to BMI. This study highlights a novel finding that sTfR is most likely a better clinical measure of iron status in inflammatory conditions as its expression is effected by erythropoiesis and not by inflammation. Risk of Acute myocardial infarction can also be predicted by increased sTfR/ferritin ratio.

Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis.

PubMed

Tonial, Cristian T; Garcia, Pedro Celiny R; Schweitzer, Louise Cardoso; Costa, Caroline A D; Bruno, Francisco; Fiori, Humberto H; Einloft, Paulo R; Garcia, Ricardo Branco; Piva, Jefferson Pedro

The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24h (D1), and 72h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p=0.046) and higher maximum inotropic score (p=0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p=0.047), pediatric intensive care unit stay (p=0.020), duration of mechanical ventilation (p=0.011), maximum inotropic score (p=0.001), and fewer ventilator-free hours (p=0.020). Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Relationship between T2* magnetic resonance imaging-derived liver and heart iron content and serum ferritin levels in transfusion-dependent thalassemic children

PubMed Central

Suthar, Kiran; Goyal, Vishnu Kumar; Sharma, Pramod; Deopa, Bindu; Rathore, Pradeep Singh; Bishnoi, Rama Krishan

2018-01-01

CONTEXT: T2* magnetic resonance imaging (MRI) is being increasingly used for the assessment of organ iron content in thalassemics, but cost is a major prohibitive factor for repeated measurements. If serum ferritin correlates well with the T2* MRI liver and heart, it will be economical and more simple tool to assess organ iron deposition. AIMS: The aim of this study was to find out the relationship between serum ferritin level and T2* MRI-derived liver and heart iron content in transfusion-dependent thalassemic children SETTINGS: Thalassemia day-care center of a teaching hospital DESIGN: This was a cross-sectional study SUBJECTS AND METHODS: Seventy-three transfusion-dependent beta thalassemic children belonging to 2–18 years of age were subjected to T2* MRI of heart and liver to assess their iron content. Values obtained here were related to serum ferritin. STATISTICAL ANALYSIS USED: Keeping the correlation between serum ferritin and T2* MRI as primary outcome, spearman's correlation coefficient was calculated. RESULTS: We found poor (negative) correlation between serum ferritin level and T2* MRI liver (r = -0.448, P = 0.000) but no correlation between serum ferritin and T2*MRI heart (r = -0.221, P = 0.060). Conclusions: Serum ferritin cannot reliably predict the liver and heart iron content in Indian children with β thalassemia. PMID:29563679

Quantitating Iron in Serum Ferritin by Use of ICP-MS

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Gillman, Patricia L.

2003-01-01

A laboratory method has been devised to enable measurement of the concentration of iron bound in ferritin from small samples of blood (serum). Derived partly from a prior method that depends on large samples of blood, this method involves the use of an inductively-coupled-plasma mass spectrometer (ICP-MS). Ferritin is a complex of iron with the protein apoferritin. Heretofore, measurements of the concentration of serum ferritin (as distinguished from direct measurements of the concentration of iron in serum ferritin) have been used to assess iron stores in humans. Low levels of serum ferritin could indicate the first stage of iron depletion. High levels of serum ferritin could indicate high levels of iron (for example, in connection with hereditary hemochromatosis an iron-overload illness that is characterized by progressive organ damage and can be fatal). However, the picture is complicated: A high level of serum ferritin could also indicate stress and/or inflammation instead of (or in addition to) iron overload, and low serum iron concentration could indicate inflammation rather than iron deficiency. Only when concentrations of both serum iron and serum ferritin increase and decrease together can the patient s iron status be assessed accurately. Hence, in enabling accurate measurement of the iron content of serum ferritin, the present method can improve the diagnosis of the patient s iron status. The prior method of measuring the concentration of iron involves the use of an atomic-absorption spectrophotometer with a graphite furnace. The present method incorporates a modified version of the sample- preparation process of the prior method. First, ferritin is isolated; more specifically, it is immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose beads. The ferritin is then separated from other iron-containing proteins and free iron by a series of centrifugation and wash steps. Next, the ferritin is digested with nitric acid

Serum ferritin values in Nigerian pregnant women.

PubMed

Nnatu, S N; Oluboyede, O A

1986-04-01

Serum ferritin values have been studied in 28 indigenous Nigerian pregnant women during the second and third trimesters of pregnancy. The mean serum ferritin value in the second trimester is higher than that in the third trimester, however, the difference is not statistically significant. When our results are related to those of Fenton and co-workers in 1977 (Fenton V, Cavill I, Fisher J: Iron stores in pregnancy. Br J Haem 37: 145, 1977) it appears that serum ferritin decreases in early pregnancy and that this decrease is maintained through the second and third trimesters and towards term, irrespective of adequate iron supplementation. It also seems that the pre-pregnancy serum ferritin level is achieved 5-8 weeks post-delivery. Our results also underline the sensitivity of serum ferritin evaluation in pregnancy, and reinforce the concept that fetal requirement for iron occurs significantly during the later half of pregnancy.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity.

PubMed

Bader, D; Blondheim, O; Jonas, R; Admoni, O; Abend-Winger, M; Reich, D; Lanir, A; Tamir, A; Eldar, I; Attias, D

1996-04-01

Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.

Ferritin: a zinc detoxicant and a zinc ion donor.

PubMed Central

Price, D; Joshi, J G

1982-01-01

Rats were injected with 1 mg of Zn2+ as zinc sulfate or 2 mg of Cd2+ as cadmium sulfate per kg of body weight on a daily basis. After seven injections, ferritin and metallothionein were isolated from the livers of the rats. Significant amounts of zinc were associated with ferritin. Incubation of such ferritin with apoenzymes of calf intestinal alkaline phosphatase, yeast phosphoglucomutase, and yeast aldolase restored their enzymic activity. The amount of zinc injected was insufficient to stimulate significant synthesis of metallothionein, but similar experiments with injection of cadmium did stimulate the synthesis of metallothionein. The amount of Zn2+ in ferritin of Cd-injected rats was greater than that in ferritin in Zn-injected rats, which was greater than that in ferritin of normal rats. Thus at comparable protein concentration ferritin from Cd-injected rats was a better Zn2+ donor than was ferritin from Zn-injected or normal animals. Ferritin is a normal constituent of several tissues, whereas metallothionein is synthesized under metabolic stress. Thus ferritin may function as a "metal storage and transferring agent" for iron and for zinc. It is suggested that ferritin probably serves as the initial chelator for Zn2+ and perhaps other metal ions as well and that under very high toxic levels of metal ions the synthesis of metallothionein is initiated as the second line of defense. PMID:6212927

Nanoscale On-Silico Electron Transport via Ferritins.

PubMed

Bera, Sudipta; Kolay, Jayeeta; Banerjee, Siddhartha; Mukhopadhyay, Rupa

2017-02-28

Silicon is a solid-state semiconducting material that has long been recognized as a technologically useful one, especially in electronics industry. However, its application in the next-generation metalloprotein-based electronics approaches has been limited. In this work, the applicability of silicon as a solid support for anchoring the iron-storage protein ferritin, which has a semiconducting iron nanocore, and probing electron transport via the ferritin molecules trapped between silicon substrate and a conductive scanning probe has been investigated. Ferritin protein is an attractive bioelectronic material because its size (X-ray crystallographic diameter ∼12 nm) should allow it to fit well in the larger tunnel gaps (>5 nm), fabrication of which is relatively more established, than the smaller ones. The electron transport events occurring through the ferritin molecules that are covalently anchored onto the MPTMS-modified silicon surface could be detected at the molecular level by current-sensing atomic force spectroscopy (CSAFS). Importantly, the distinct electronic signatures of the metal types (i.e., Fe, Mn, Ni, and Au) within the ferritin nanocore could be distinguished from each other using the transport band gap analyses. The CSAFS measurements on holoferritin, apoferritin, and the metal core reconstituted ferritins reveal that some of these ferritins behave like n-type semiconductors, while the others behave as p-type semiconductors. The band gaps for the different ferritins are found to be within 0.8 to 2.6 eV, a range that is valid for the standard semiconductor technology (e.g., diodes based on p-n junction). The present work indicates effective on-silico integration of the ferritin protein, as it remains functionally viable after silicon binding and its electron transport activities can be detected. Potential use of the ferritin-silicon nanohybrids may therefore be envisaged in applications other than bioelectronics, too, as ferritin is a versatile

Iron binding to human heavy-chain ferritin.

PubMed

Pozzi, Cecilia; Di Pisa, Flavio; Bernacchioni, Caterina; Ciambellotti, Silvia; Turano, Paola; Mangani, Stefano

2015-09-01

Maxi-ferritins are ubiquitous iron-storage proteins with a common cage architecture made up of 24 identical subunits of five α-helices that drive iron biomineralization through catalytic iron(II) oxidation occurring at oxidoreductase sites (OS). Structures of iron-bound human H ferritin were solved at high resolution by freezing ferritin crystals at different time intervals after exposure to a ferrous salt. Multiple binding sites were identified that define the iron path from the entry ion channels to the oxidoreductase sites. Similar data are available for another vertebrate ferritin: the M protein from Rana catesbeiana. A comparative analysis of the iron sites in the two proteins identifies new reaction intermediates and underlines clear differences in the pattern of ligands that define the additional iron sites that precede the oxidoreductase binding sites along this path. Stopped-flow kinetics assays revealed that human H ferritin has different levels of activity compared with its R. catesbeiana counterpart. The role of the different pattern of transient iron-binding sites in the OS is discussed with respect to the observed differences in activity across the species.

Association between serum ferritin and glaucoma in the South Korean population.

PubMed

Lin, Shuai-Chun; Wang, Sophia Y; Yoo, Chungkwon; Singh, Kuldev; Lin, Shan C

2014-12-01

Evidence suggests that altered iron metabolism may be associated with oxidative damage to several organ systems, including the eye. Supplementary iron consumption is also associated with greater odds of self-reported glaucoma. To investigate the association between serum ferritin level and the likelihood of a glaucoma diagnosis in a cross-sectional, population-based study. Data were collected from 17,476 participants in the first and second years of the Fifth Korea National Health and Nutrition Examination Survey, a cross-sectional study of the South Korean population conducted from January 1, 2010, through December 31, 2011. Data pertaining to the serum ferritin level were aggregated and divided into quartiles. Demographic, comorbidity, and health-related behavior information was obtained via interview. The presence or absence of glaucoma. The definition of glaucoma was based on criteria established by the International Society of Geographical and Epidemiological Ophthalmology. Participants whose serum ferritin level was greater than 61 ng/mL (to convert to picomoles per liter, multiply by 2.247) had significantly higher odds of a glaucoma diagnosis when compared with those with a level less than 31 ng/mL, after adjustment for potential confounders (ferritin levels of 31-61 ng/mL: odds ratio [OR], 1.17; 95% CI, 0.84-1.62; ferritin levels of 62-112 ng/mL: OR, 1.60; 95% CI, 1.16-2.20; and ferritin levels of 113-3018 ng/mL: OR, 1.89; 95% CI, 1.32-2.72). Our study reveals that a higher serum ferritin level was associated with greater odds of glaucoma in a representative sample of the South Korean population, even at levels normally observed in the general population. This novel finding may help elucidate the pathogenesis and lead to novel therapeutic approaches for glaucomatous disease.

Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis.

PubMed

Yeap, Bu B; Divitini, Mark L; Gunton, Jenny E; Olynyk, John K; Beilby, John P; McQuillan, Brendan; Hung, Joseph; Knuiman, Matthew W

2015-04-01

Iron overload predisposes to diabetes and higher ferritin levels have been associated with diabetes. However, it is unclear whether ferritin reflects differences in iron-related parameters between diabetic and nondiabetic persons. We examined associations of serum ferritin, iron and transferrin saturation with Type 2 diabetes in adults without genetic predisposition to iron overload. Cross-sectional analysis of community-dwelling men and women aged 17-97 years from the Busselton Health Survey, Western Australia. Men and women carrying genotypes associated with haemochromatosis (C282Y/C282Y or C282Y/H63D) were excluded. Serum ferritin, iron and transferrin saturation were assayed. There were 1834 men (122 with diabetes, 6·6%) and 2351 women (141 with diabetes, 6%). In men, higher serum ferritin was associated with diabetes after adjusting for age, smoking, alcohol, cardiovascular history, body mass index (BMI), waist, blood pressure, lipids, C-reactive protein (CRP), adiponectin, alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) [odds ratio (OR): 1·29 per 1 unit increase log ferritin, 95% confidence interval (CI) = 1·01-1·65, P = 0·043]. In women, higher serum ferritin was associated with diabetes [fully adjusted OR: 1·31 per 1 unit increase log ferritin, 95% CI = 1·04-1·63, P = 0·020; 1·84 for tertile (T) 3 vs T1, 95% CI = 1·09-3·11]. Neither iron levels nor transferrin saturation were associated with diabetes risk in men or women. Higher ferritin was not associated with insulin resistance in nondiabetic adults. In adults, higher ferritin levels are independently associated with prevalent diabetes while iron and transferrin saturation are not. Ferritin is a robust biomarker for diabetes risk, but further investigation is needed to clarify whether this relationship is mediated via iron metabolism. © 2014 John Wiley & Sons Ltd.

Association of serum ferritin with metabolic syndrome and diabetes mellitus in the South Korean general population according to the Korean National Health and Nutrition Examination Survey 2008.

PubMed

Lee, Byung-Kook; Kim, Yangho; Kim, Young-Il

2011-10-01

We examined the association of serum ferritin levels with metabolic syndrome (MS) and diabetes mellitus in a representative sample of the adult South Korean population using data from the 2008 Korean National Health and Nutrition Examination Survey. We conducted a cross-sectional study of 6311 adults older than 20 years who participated in the 2008 Korean National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least 3 of the following: elevated blood pressure, low high-density lipoprotein cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Diabetes mellitus was defined as fasting glucose of at least 126 mg/dL. Insulin resistance was determined using the homeostasis model assessment estimate of insulin resistance. In a representative sample of the adult Korean population, MS was more prevalent in the highest quartile compared with the lowest quartile of serum ferritin concentrations in women following adjustments for age, education, smoking, alcohol intake, body mass index, aspartate aminotransferase, and alanine aminotransferase. Diabetes mellitus was more prevalent in the highest quartile compared with the lowest quartile of serum ferritin concentrations in premenopausal women and men. The geometric means of fasting insulin and insulin resistance determined using the homeostasis model assessment of insulin resistance in the fourth serum ferritin quartiles of postmenopausal women and men were significantly higher compared with those in the first quartile of the respective groups. The present study demonstrates that elevated serum ferritin concentrations are associated with an increased risk of MS and diabetes mellitus in a representative sample of the adult South Korean population. Copyright © 2011. Published by Elsevier Inc.

Abnormal troponin I levels in a thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-01-21

Thalassemia is a congenital hemoglobinopathy leading to anemia because of impaired erythropoiesis and peripheral hemolysis. Thalassemia major patients are transfusion dependent and it results in iron accumulation. The heart is one of the major organs affected with iron overload and iron induced cardiac dysfunction (pump and conduction abnormalities) remains the number one cause of death among thalassemia major patients. It has been reported that a high ferritin concentration is related to high troponin levels in hemodialysis patients receiving more intravenous iron sucrose. Abnormal troponin I levels have also been reported without acute coronary syndrome. We present a case of abnormal troponin I levels in Thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome. To our knowledge, this is the first report of abnormal troponin I levels in a Thalassemia major patient with high ferritin concentration and without acute coronary syndrome and also this case focuses attention on the importance of the correct evaluation of abnormal troponin I levels. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia.

PubMed

Cheong, June-Won; Kim, Hyeoung-Joon; Lee, Kyoo-Hyung; Yoon, Sung-Soo; Lee, Jae Hoon; Park, Hee-Sook; Kim, Ho Young; Shim, Hyeok; Seong, Chu-Myung; Kim, Chul Soo; Chung, Jooseop; Hyun, Myung Soo; Jo, Deog-Yeon; Jung, Chul Won; Sohn, Sang Kyun; Yoon, Hwi-Joong; Kim, Byung Soo; Joo, Young-Don; Park, Chi-Young; Min, Yoo Hong

2014-06-01

Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA). This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA. A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline. This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented. © 2013 AABB.

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

PubMed Central

Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit.

PubMed

Zhang, Yinghui; Mikhael, Marc; Xu, Dongxue; Li, Yiye; Soe-Lin, Shan; Ning, Bo; Li, Wei; Nie, Guangjun; Zhao, Yuliang; Ponka, Prem

2010-10-01

Cytosolic ferritins sequester and store iron, consequently protecting cells against iron-mediated free radical damage. However, the mechanisms of iron exit from the ferritin cage and reutilization are largely unknown. In a previous study, we found that mitochondrial ferritin (MtFt) expression led to a decrease in cytosolic ferritin. Here we showed that treatment with inhibitors of lysosomal proteases largely blocked cytosolic ferritin loss in both MtFt-expressing and wild-type cells. Moreover, cytosolic ferritin in cells treated with inhibitors of lysosomal proteases was found to store more iron than did cytosolic ferritins in untreated cells. The prevention of cytosolic ferritin degradation in MtFt-expressing cells significantly blocked iron mobilization from the protein cage induced by MtFt expression. These studies also showed that blockage of cytosolic ferritin loss by leupeptin resulted in decreased cytosolic ferritin synthesis and prolonged cytosolic ferritin stability, potentially resulting in diminished iron availability. Lastly, we found that proteasomes were responsible for cytosolic ferritin degradation in cells pretreated with ferric ammonium citrate. Thus, the current studies suggest that cytosolic ferritin degradation precedes the release of iron in MtFt-expressing cells; that MtFt-induced cytosolic ferritin decrease is partially preventable by lysosomal protease inhibitors; and that both lysosomal and proteasomal pathways may be involved in cytosolic ferritin degradation.

Multilayer Ferritin Array for Bionanobattery

NASA Technical Reports Server (NTRS)

Chu, Sang-Hyon (Inventor); Choi, Sang H. (Inventor); Kim, Jae-Woo (Inventor); Lillehei, Peter T. (Inventor); Park, Yeonjoon (Inventor); King, Glen C. (Inventor); Elliott, James R., Jr. (Inventor)

2009-01-01

A thin-film electrode for a bio-nanobattery is produced by consecutively depositing arrays of a ferritin protein on a substrate, employing a spin self-assembly procedure. By this procedure, a first ferritin layer is first formed on the substrate, followed by building a second, oppositely-charged ferritin layer on the top of the first ferritin layer to form a bilayer structure. Oppositely-charged ferritin layers are subsequently deposited on top of each other until a desired number of bilayer structures is produced. An ordered, uniform, stable and robust, thin-film electrode material of enhanced packing density is presented, which provides optimal charge density for the bio-nanobattery.

Iron Induction of Ferritin Synthesis in Soybean Cell Suspensions

PubMed Central

Proudhon, Dominique; Briat, Jean-François; Lescure, Anne-Marie

1989-01-01

In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes. Images Figure 2 Figure 3 Figure 5 PMID:16666812

Iron induction of ferritin synthesis in soybean cell suspensions.

PubMed

Proudhon, D; Briat, J F; Lescure, A M

1989-06-01

In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes.

Regulatory effects of ferritin on angiogenesis

PubMed Central

Coffman, Lan G.; Parsonage, Derek; D'Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2009-01-01

Angiogenesis, the synthesis of new blood vessels from preexisting vessels, plays a critical role in normal wound healing and tumor growth. HKa (cleaved high molecular weight kininogen) is an endogenous inhibitor of angiogenesis formed by the cleavage of kininogen on endothelial cells. Ferritin is a protein principally known for its central role in iron storage. Here, we demonstrate that ferritin binds to HKa with high affinity (Kd 13 nM). Further, ferritin antagonizes the antiangiogenic effects of HKa, enhancing the migration, assembly, and survival of HKa-treated endothelial cells. Effects of ferritin were independent of its iron content. Peptide mapping revealed that ferritin binds to a 22-aa subdomain of HKa that is critical to its antiangiogenic activity. In vivo, ferritin opposed HKa's antiangiogenic effects in a human prostate cancer xenograft, restoring tumor-dependent vessel growth. Ferritin-mediated regulation of angiogenesis represents a new angiogenic regulatory pathway, and identifies a new role for ferritin in cell biology. PMID:19126685

Association of low ferritin with PLM in the Wisconsin Sleep Cohort.

PubMed

Li, Jason; Moore, Hyatt; Lin, Ling; Young, Terry; Finn, Laurel; Peppard, Paul E; Mignot, Emmanuel

2015-11-01

The origins of periodic leg movements (PLMs), a strong correlate of restless legs syndrome (RLS), are uncertain. This study was performed to assess the relationship between PLMs and peripheral iron deficiency, as measured with ferritin levels corrected for inflammation. We included a cross-sectional sample of a cohort study of 801 randomly selected people (n = 1008 assays, mean age 58.6 ± 0.3 years) from Wisconsin state employee agencies. A previously validated automatic detector was used to measure PLMs during sleep. The patients were categorized into RLS symptoms-positive and RLS symptoms-negative based on a mailed survey response and prior analysis. Analyses were performed using a linear model with PLM category above and below 15 PLM/h (periodic leg movement index, PLMI) as the dependent variable, and adjusting for known covariates, including previously associated single-nucleotide polymorphisms (SNPs) within BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Ferritin and C-reactive protein (CRP) levels were measured in serum, and ferritin levels corrected for inflammation using CRP levels. After controlling for cofactors, PLMI ≥ 15 was associated with low (≤50 ng/mL) ferritin levels (OR = 1.55, p = 0.020). The best model was found using quasi-least squares regression of ferritin as a function of PLMI, with an increase of 0.0034 PLM/h predicted by a decrease of 1 ng/mL ferritin (p = 0.00447). An association was found between low ferritin and greater PLMs in a general population of older adults, independent of genetic polymorphisms, suggesting a role of low iron stores in the expression of these phenotypes. Patients with high PLMI may require to be checked for iron deficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 μg/L at diagnosis.

PubMed

Barton, James C; Barton, J Clayborn; Acton, Ronald T; So, Jeffrey; Chan, Susanne; Adams, Paul C

2012-04-01

We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 μg/L at diagnosis. We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 μg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 μg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 μg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 μg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 μg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with

Effect of RBC concentrate transfusions on serum ferritin content in children with acute leukaemia.

PubMed

Bebeshko, V G; Bruslova, E M; Tsvietkova, N M; Iatsemirskii, S M; Puchkareva, T I; Gonchar, L A; Krukovska, V V; Zelinska, A V; Mishchenko, L P

2013-01-01

To study the serum ferritin levels in children with acute leukemia, depending on the number of transfusions of RBC concentrate and period of disease. We studied the red blood count, serum iron and ferritin levels in 54 patients with acute leukemia before chemotherapy, at the time of a standardized treatment protocol, and after transfusions of RBC concentrates. In the debute of acute leukemia just before treatment lauch the serum ferritin in 81.5% of children was 2.3-2.5 higher than normal. The need for transfusion of RBC concentrates was higher under serum ferritin level exceeding 500 ng/mL. The association was established between ferritin content and age of the children, variant of acute leukemia and period of the disease. The level of serum ferritin can be used as a marker of ferrokinetic status for timely diagnosis of iron overload in children with acute leukemias and for application of treatment-and-prophylactic actions. Bebeshko V. G., Bruslova K. M., Cvjetkova N. M., Jacemyrskyj S. M., Pushkarova T. I., Gonchar L. O., Krukovska V. V., Zelinska A. V., Mishhenko L. P., 2013.

Abscisic acid is involved in the iron-induced synthesis of maize ferritin.

PubMed Central

Lobréaux, S; Hardy, T; Briat, J F

1993-01-01

The ubiquitous iron storage protein ferritin has a highly conserved structure in plants and animals, but a distinct cytological location and a different level of control in response to iron excess. Plant ferritins are plastid-localized and transcriptionally regulated in response to iron, while animal ferritins are found in the cytoplasm and have their expression mainly controlled at the translational level. In order to understand the basis of these differences, we developed hydroponic cultures of maize plantlets which allowed an increase in the intracellular iron concentration, leading to a transient accumulation of ferritin mRNA and protein (Lobréaux,S., Massenet,O. and Briat,J.F., 1992, Plant Mol. Biol., 19, 563-575). Here, it is shown that iron induces ferritin and RAB (Responsive to Abscisic Acid) mRNA accumulation relatively with abscisic acid (ABA) accumulation. Ferritin mRNA also accumulates in response to exogenous ABA. Synergistic experiments demonstrate that the ABA and iron responses are linked, although full expression of the ferritin genes cannot be entirely explained by an increase in ABA concentration. Inducibility of ferritin mRNA accumulation by iron is dramatically decreased in the maize ABA-deficient mutant vp2 and can be rescued by addition of exogenous ABA, confirming the involvement of ABA in the iron response in plants. Therefore, it is concluded that a major part of the iron-induced biosynthesis of ferritin is achieved through a pathway involving an increase in the level of the plant hormone ABA. The general conclusion of this work is that the synthesis of the same protein in response to the same environmental signal can be controlled by separate and distinct mechanisms in plants and animals. Images PMID:8440255

Serum ferritin: Past, present and future.

PubMed

Wang, Wei; Knovich, Mary Ann; Coffman, Lan G; Torti, Frank M; Torti, Suzy V

2010-08-01

Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. Copyright 2010 Elsevier B.V. All rights reserved.

Electrostatic placement of single ferritin molecules

NASA Astrophysics Data System (ADS)

Kumagai, Shinya; Yoshii, Shigeo; Yamada, Kiyohito; Matsukawa, Nozomu; Fujiwara, Isamu; Iwahori, Kenji; Yamashita, Ichiro

2006-04-01

We electrostatically placed a single ferritin molecule on a nanometric 3-aminopropyltriethoxysilane (APTES) pattern that was on an oxidized Si substrate. The numerical analysis of the total interaction free energy for ferritin predicted that a quadrilateral array of 15nm diameter APTES nanodisks placed at intervals of 100nm would accommodate a single molecule of ferritin in each disk under a Debye length of 14nm. The experiments we conducted conformed to theoretical predictions and we successfully placed a single ferritin molecule on each ATPES disk without ferritin adsorbing on the SiO2 substrate surface.

Serum Ferritin: Past, Present and Future

PubMed Central

Wang, Wei; Knovich, Mary Ann; Coffman, Lan G.; Torti, Frank M.; Torti, Suzy V.

2010-01-01

Background Serum ferritin was discovered in the 1930’s, and was developed as a clinical test in the 1970’s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. Scope of Review In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Major Conclusions Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. General Significance Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. PMID:20304033

Insect Ferritins: typical or atypical?

PubMed Central

Pham, Daphne Q. D.; Winzerling, Joy J.

2010-01-01

Insects transmit millions of cases of disease each year, and cost millions of dollars in agricultural losses. The control of insect-borne diseases is vital for numerous developing countries, and the management of agricultural insect pests is a very serious business for developed countries. Control methods should target insect-specific traits in order to avoid non-target effects, especially in mammals. Since insect cells have had a billion years of evolutionary divergence from those of vertebrates, they differ in many ways that might be promising for the insect control field—especially, in iron metabolism because current studies have indicated that significant differences exist between insect and mammalian systems. Insect iron metabolism differs from that of vertebrates in the following respects. Insect ferritins have a heavier mass than mammalian ferritins. Unlike their mammalian counterparts, the insect ferritin subunits are often glycosylated and are synthesized with a signal peptide. The crystal structure of insect ferritin also shows a tetrahedral symmetry consisting of 12 heavy chain and 12 light chain subunits in contrast to that of mammalian ferritin that exhibits an octahedral symmetry made of 24 heavy chain and 24 light chain subunits. Insect ferritins associate primarily with the vacuolar system and serve as iron transporters—quite the opposite of the mammalian ferritins, which are mainly cytoplasmic and serve as iron storage proteins. This review will discuss these differences. PMID:20230873

Ferritin Assembly in Enterocytes of Drosophila melanogaster

PubMed Central

Rosas-Arellano, Abraham; Vásquez-Procopio, Johana; Gambis, Alexis; Blowes, Liisa M.; Steller, Hermann; Mollereau, Bertrand; Missirlis, Fanis

2016-01-01

Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH) and Ferritin 2 Light Chain Homolog (Fer2LCH) are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated. PMID:26861293

H-Ferritin Is Preferentially Incorporated by Human Erythroid Cells through Transferrin Receptor 1 in a Threshold-Dependent Manner

PubMed Central

Sakamoto, Soichiro; Kawabata, Hiroshi; Masuda, Taro; Uchiyama, Tatsuki; Mizumoto, Chisaki; Ohmori, Katsuyuki; Koeffler, H. Phillip; Kadowaki, Norimitsu; Takaori-Kondo, Akifumi

2015-01-01

Ferritin is an iron-storage protein composed of different ratios of 24 light (L) and heavy (H) subunits. The serum level of ferritin is a clinical marker of the body’s iron level. Transferrin receptor (TFR)1 is the receptor not only for transferrin but also for H-ferritin, but how it binds two different ligands and the blood cell types that preferentially incorporate H-ferritin remain unknown. To address these questions, we investigated hematopoietic cell-specific ferritin uptake by flow cytometry. Alexa Fluor 488-labeled H-ferritin was preferentially incorporated by erythroid cells among various hematopoietic cell lines examined, and was almost exclusively incorporated by bone marrow erythroblasts among human primary hematopoietic cells of various lineages. H-ferritin uptake by erythroid cells was strongly inhibited by unlabeled H-ferritin but was only partially inhibited by a large excess of holo-transferrin. On the other hand, internalization of labeled holo-transferrin by these cells was not inhibited by H-ferritin. Chinese hamster ovary cells lacking functional endogenous TFR1 but expressing human TFR1 with a mutated RGD sequence, which is required for transferrin binding, efficiently incorporated H-ferritin, indicating that TFR1 has distinct binding sites for H-ferritin and holo-transferrin. H-ferritin uptake by these cells required a threshold level of cell surface TFR1 expression, whereas there was no threshold for holo-transferrin uptake. The requirement for a threshold level of TFR1 expression can explain why among primary human hematopoietic cells, only erythroblasts efficiently take up H-ferritin. PMID:26441243

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

PubMed Central

Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

2015-01-01

Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

Iron, ferritin, and nutrition.

PubMed

Theil, Elizabeth C

2004-01-01

Ferritin, a major form of endogenous iron in food legumes such as soybeans, is a novel and natural alternative for iron supplementation strategies where effectiveness is limited by acceptability, cost, or undesirable side effects. A member of the nonheme iron group of dietary iron sources, ferritin is a complex with Fe3+ iron in a mineral (thousands of iron atoms inside a protein cage) protected from complexation. Ferritin illustrates the wide range of chemical and biological properties among nonheme iron sources. The wide range of nonheme iron receptors matched to the structure of the iron complexes that occurs in microorganisms may, by analogy, exist in humans. An understanding of the chemistry and biology of each type of dietary iron source (ferritin, heme, Fe2+ ion, etc.), and of the interactions dependent on food sources, genes, and gender, is required to design diets that will eradicate global iron deficiency in the twenty-first century.

Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.

PubMed

Jacobs, Esther M G; Hendriks, Jan C M; van Deursen, Cees Th B M; Kreeftenberg, Herman G; de Vries, Richard A; Marx, Joannes J M; Stalenhoef, Anton F H; Verbeek, André L M; Swinkels, Dorine W

2009-01-01

In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH. Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS). The best predictive multivariable model forecasted 45% of variation of the serum ferritin levels. In this model severity of iron overload in the proband significantly predicted serum ferritin levels in FDFM. Other significant determinants in this model consisted of C282Y homozygosity, compound heterozygosity, age at testing for serum ferritin and supplemental iron intake, whereas a low body mass index showed a protective effect. This study provides a model to assess the risk of development of iron overload for relatives of probands with HH. These results might be instrumental in the development of an optimal strategy for future family screening programs.

Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

PubMed Central

Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

2016-01-01

Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome

PubMed Central

Cozzi, Anna; Santambrogio, Paolo; Privitera, Daniela; Broccoli, Vania; Rotundo, Luisa Ida; Garavaglia, Barbara; Benz, Rudolf; Altamura, Sandro; Goede, Jeroen S.; Muckenthaler, Martina U.

2013-01-01

The ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient’s fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS. PMID:23940258

Short repeats in the heme oxygenase 1 gene promoter is associated with increased levels of inflammation, ferritin and higher risk of type-2 diabetes mellitus.

PubMed

Andrews, Mónica; Leiva, Elba; Arredondo-Olguín, Miguel

2016-09-01

We evaluated the relationship between the HO1 genotype, ferritin levels and the risk of type-2 diabetes and inflammation. Eight hundred thirty-five individuals were evaluated and classified according to their nutritional status and the presence of type-2 diabetes: 153 overweight (OW); 62 obese (OB); 55 type-2 diabetes mellitus (DM); 202 OWDM; 239 OBDM and 124 controls (C). We studied biochemical (glycemia, insulin, lipid profile, liver enzyme, creatinine, hsCRP), hematological (hemoglobin, free erythrocyte protoporphyrin, transferrin receptor and serum Fe and ferritin) and oxidative stress (SOD, GHS and TBARS) parameters. We determined heme oxygenase activity and the (GT)n polymorphism in its gene promoter. Individuals with diabetes, independent of nutritional status, showed high levels of ferritin and HO activity compared to control subjects. Allelic frequency was not different between the groups (Chi(2), NS) however, genotypes were different (Chi(2), P<0.001). The SS (short-short) genotype was higher in all DM individuals compared to controls and MM was higher in controls. SM (short-medium) genotype was an independent risk factor for DM in logistic regression analysis. We observed high risk for type-2 diabetes mellitus in the presence of SM genotype and high levels of ferritin (OR adjusted: 2.7; 1.9-3.6; p<0.001; compared to control group). It was also significantly related to inflammation. The SM genotype in HO1 gene promoter and ferritin levels were associated with higher risk for type-2 diabetes and for having a higher marker of inflammation, which is the main risk factor for the development of chronic diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

Solving Biology's Iron Chemistry Problem with Ferritin Protein Nanocages.

PubMed

Theil, Elizabeth C; Tosha, Takehiko; Behera, Rabindra K

2016-05-17

Ferritins reversibly synthesize iron-oxy(ferrihydrite) biominerals inside large, hollow protein nanocages (10-12 nm, ∼480 000 g/mol); the iron biominerals are metabolic iron concentrates for iron protein biosyntheses. Protein cages of 12- or 24-folded ferritin subunits (4-α-helix polypeptide bundles) self-assemble, experimentally. Ferritin biomineral structures differ among animals and plants or bacteria. The basic ferritin mineral structure is ferrihydrite (Fe2O3·H2O) with either low phosphate in the highly ordered animal ferritin biominerals, Fe/PO4 ∼ 8:1, or Fe/PO4 ∼ 1:1 in the more amorphous ferritin biominerals of plants and bacteria. While different ferritin environments, plant bacterial-like plastid organelles and animal cytoplasm, might explain ferritin biomineral differences, investigation is required. Currently, the physiological significance of plant-specific and animal-specific ferritin iron minerals is unknown. The iron content of ferritin in living tissues ranges from zero in "apoferritin" to as high as ∼4500 iron atoms. Ferritin biomineralization begins with the reaction of Fe(2+) with O2 at ferritin enzyme (Fe(2+)/O oxidoreductase) sites. The product of ferritin enzyme activity, diferric oxy complexes, is also the precursor of ferritin biomineral. Concentrations of Fe(3+) equivalent to 2.0 × 10(-1) M are maintained in ferritin solutions, contrasting with the Fe(3+) Ks ∼ 10(-18) M. Iron ions move into, through, and out of ferritin protein cages in structural subdomains containing conserved amino acids. Cage subdomains include (1) ion channels for Fe(2+) entry/exit, (2) enzyme (oxidoreductase) site for coupling Fe(2+) and O yielding diferric oxy biomineral precursors, and (3) ferric oxy nucleation channels, where diferric oxy products from up to three enzyme sites interact while moving toward the central, biomineral growth cavity (12 nm diameter) where ferric oxy species, now 48-mers, grow in ferric oxy biomineral. High ferritin protein

Secreted ferritin arises from the entry of newly translated ferritin chains into the secretory apparatus in response to a deficiency in free cytosolic iron

PubMed Central

De Domenico, Ivana; Vaughn, Michael B; Paradkar, Prasad N; Lo, Eric; Ward, Diane M.; Kaplan, Jerry

2010-01-01

Summary Ferritin is a multisubunit protein that is responsible for storing and detoxifying cytosolic iron. Ferritin can be found in serum but is relatively iron poor. Serum ferritin occurs in iron overload disorders, inflammation and in the genetic disorder hyperferritinemia with cataracts. We show that ferritin secretion results when cellular ferritin synthesis occurs in the relative absence of free cytosolic iron. In yeast and mammalian cells, newly synthesized ferritin monomers can be translocated into the endoplasmic reticulum and transits through the secretory apparatus. Ferritin chains can be translocated into the endoplasmic reticulum in an in vitro translation and membrane insertion system. The insertion of ferritin monomers into the ER occurs under low free iron conditions, as iron will induce the assembly of ferritin. Secretion of ferritin chains provides a mechanism that limits ferritin nanocage assembly and ferritin mediated-iron sequestration in the absence of the translational inhibition of ferritin synthesis. PMID:21195349

High ferritin levels have major effects on the morphology of erythrocytes in Alzheimer's disease.

PubMed

Bester, Janette; Buys, Antoinette V; Lipinski, Boguslaw; Kell, Douglas B; Pretorius, Etheresia

2013-01-01

Unliganded iron both contributes to the pathology of Alzheimer's disease (AD) and also changes the morphology of erythrocytes (RBCs). We tested the hypothesis that these two facts might be linked, i.e., that the RBCs of AD individuals have a variant morphology, that might have diagnostic or prognostic value. We included a literature survey of AD and its relationships to the vascular system, followed by a laboratory study. Four different microscopy techniques were used and results statistically compared to analyze trends between high and normal serum ferritin (SF) AD individuals. Light and scanning electron microscopies showed little difference between the morphologies of RBCs taken from healthy individuals and from normal SF AD individuals. By contrast, there were substantial changes in the morphology of RBCs taken from high SF AD individuals. These differences were also observed using confocal microscopy and as a significantly greater membrane stiffness (measured using force-distance curves). We argue that high ferritin levels may contribute to an accelerated pathology in AD. Our findings reinforce the importance of (unliganded) iron in AD, and suggest the possibility both of an early diagnosis and some means of treating or slowing down the progress of this disease.

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta-analysis.

PubMed

Fernández-Cao, José C; Aranda, Núria; Ribot, Blanca; Tous, Mònica; Arija, Victoria

2017-10-01

The aim of this systematic review and meta-analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand-searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse-variance using fixed-effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta-analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23-1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48-2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I 2  = 33.3%, P = 0.151) and ferritin (I 2  = 0.7%, P = 0.418) meta-analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM. © 2016 John Wiley & Sons Ltd.

The effect of charge on the renal distribution of ferritin.

PubMed

Cohen, S; Vernier, R L; Michael, A F

1983-02-01

The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in

Metal Sulfide Nanocrystals inside Ferritin with Photovoltaic Applications

NASA Astrophysics Data System (ADS)

Hansen, Kameron; Peterson, J. Ryan; Olsen, Cameron; Hogg, Heather; Colton, John; Watt, Richard; Colton Team

Ferritin is a spherical protein shell used universally by organisms to store iron. Due to a number of ferritin's properties (a conductive shell, ability to be arranged in ordered arrays, and high stability), recent theoretical work has proposed that non-native semiconductor nanocrystals inside ferritin can be used for high-efficiency solar energy conversion. We present research on the synthesis of a variety of these nanocrystals (PbS, CuS, Mo2S, ZnS, and PbSe) inside ferritin's hollow interior and band gap energies of the resulting ferritin-nanocrystal constructs. We also report preliminary solar cell results for dye sensitized solar cells with PbS-ferritin as the dye.

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease.

PubMed

Koppe, Tiago; Doneda, Divair; Siebert, Marina; Paskulin, Livia; Camargo, Matheus; Tirelli, Kristiane Michelin; Vairo, Filippo; Daudt, Liane; Schwartz, Ida Vanessa D

2016-03-01

The clinical utility of serum ferritin as a biomarker of disease severity and prognosis in Gaucher disease (GD) is still debated. Here, we aimed to evaluate ferritin and its relation to clinicolaboratory parameters of GD patients seen at the Reference Center for Gaucher Disease of Rio Grande do Sul, Brazil, so as to gather evidence on the utility of ferritin as a biomarker of this condition. A retrospective chart review was performed collecting pre-and posttreatment data from GD patients. Eighteen patients with ferritin levels available before and after treatment were included in the study. Nine of these participants were males, and seventeen had type I GD. All patients were given either enzyme replacement (n = 16) or substrate reduction therapy (n = 2), and ferritin was found to decrease from 756 [318-1441] ng/mL at baseline to 521 [227-626] ng/mL (p=0.025) after 28.8 month soft treatment. Serum ferritin levels did not correlate with measures of disease severity, but showed an association with age at onset of treatment (ρ= 0.880; n = 18; p < 0.001). In conclusion, although serum ferritin did not correlate with disease severity, after a median 28.8 months of treatment, clinical outcomes had clearly improved, and ferritin levels had decreased.

Serum ferritin concentration in sickle cell crisis.

PubMed Central

Brownell, A; Lowson, S; Brozović, M

1986-01-01

Serum ferritin, aspartate aminotransferase (AST), alkaline phosphatase and hydroxybutyrate dehydrogenase (HBD) were studied during 21 vaso-occlusive crises in 12 adults with sickle cell disease (11 SS, 1 S beta degrees). The patients comprised three groups: those who had been untransfused (4), those who had received occasional exchange transfusion in crisis (3), and those who had been multiply transfused (5). Serum ferritin concentrations in crisis were compared with those of the steady state value. Rises in serum ferritin concentrations occurred in all crises in all groups. Although AST, alkaline phosphatase, and HBD rose, there was no correlation between these and log ferritin concentrations. The clinical impression was that the degree of rise in ferritin related to the severity of the particular crisis, and the above results showed that haemolysis and liver damage were not causally related to this rise. An estimate of serum ferritin cannot be used to assess the state of iron balance in sickle cell disease unless the patient is in the steady state. The considerable rise in serum ferritin concentration found in crisis, however, may be a useful marker of the extent of vaso-occlusion and tissue damage. PMID:3958215

Ferritin and bile acid levels during the intrauterine pre-treatment of gastroschisis by serial amnioexchange

PubMed Central

Demir, Namık; Canda, Mehmet Tunç; Kuday, Şamil; Öztürk, Cengiz; Sezer, Orçun; Danaoğlu, Nihal

2013-01-01

We present a case of gastroschisis managed with serial amnioex-changes. Marked decreases were detected in both ferritin and bile acid levels following the procedure. The bowels were not severely affected, as expected. After delivery, single primary closure of the defect was performed. Early enteral feeding and shorter hospital stay were the main outcome measures. Intrauterine pre-treatment of gastroschisis by serial amnioexchange may provide benefits by decreasing the levels of inflammatory products in the amniotic fluid in order to lower the possible risk of bowel damage, and this may help to achieve better surgical and postnatal outcomes. PMID:24592073

Distinguishing ferritin from apoferritin using magnetic force microscopy

NASA Astrophysics Data System (ADS)

Nocera, Tanya M.; Zeng, Yuzhi; Agarwal, Gunjan

2014-11-01

Estimating the amount of iron-replete ferritin versus iron-deficient apoferritin proteins is important in biomedical and nanotechnology applications. This work introduces a simple and novel approach to quantify ferritin by using magnetic force microscopy (MFM). We demonstrate how high magnetic moment probes enhance the magnitude of MFM signal, thus enabling accurate quantitative estimation of ferritin content in ferritin/apoferritin mixtures in vitro. We envisage MFM could be adapted to accurately determine ferritin content in protein mixtures or in small aliquots of clinical samples.

Ferritins: dynamic management of biological iron and oxygen chemistry.

PubMed

Liu, Xiaofeng; Theil, Elizabeth C

2005-03-01

Ferritins are spherical, cage-like proteins with nanocavities formed by multiple polypeptide subunits (four-helix bundles) that manage iron/oxygen chemistry. Catalytic coupling yields diferric oxo/hydroxo complexes at ferroxidase sites in maxi-ferritin subunits (24 subunits, 480 kDa; plants, animals, microorganisms). Oxidation occurs at the cavity surface of mini-ferritins/Dps proteins (12 subunits, 240 kDa; bacteria). Oxidation products are concentrated as minerals in the nanocavity for iron-protein cofactor synthesis (maxi-ferritins) or DNA protection (mini-ferritins). The protein cage and nanocavity characterize all ferritins, although amino acid sequences diverge, especially in bacteria. Catalytic oxidation/di-iron coupling in the protein cage (maxi-ferritins, 480 kDa; plants, bacteria and animal cell-specific isoforms) or on the cavity surface (mini-ferritins/Dps proteins, 280 kDa; bacteria) initiates mineralization. Gated pores (eight or four), symmetrically arranged, control iron flow. The multiple ferritin functions combine pore, channel, and catalytic functions in compact protein structures required for life and disease response.

Macroscopic quantum coherence in ferritin

NASA Astrophysics Data System (ADS)

Garg, Anupam

1996-04-01

In a breakthrough experiment, Awschalom et al. [ Phys. Rev. Lett. 68, 3092 (1992)] have demonstrated that the antiferromagnetic core in ferritin resonates between two states with oppositely directed Néel vectors, making it the first observation of MQC. A theory has been developed for this resonance including the effect of the 100 or so57Fe nuclear spins expected in each ferritin core. Since the hyperfine coupling is known to be ˜68 MHz and the MQC frequency is ˜1 MHz, the degeneracy of the Néel states, and with it, the MQC resonance, is destroyed in all ferritin particles except those with zero total staggered nuclear spin. From the measured size of λ″(ω), the energy being absorbed by the ferritin is at least 4000 times larger than the maximum permissible. Hence, the true importance of these experiments lies not in the narrow issue of MQC, but in the disproof of long cherished theoretical conservation laws.

Photoreduction and incorporation of iron into ferritins.

PubMed Central

Laulhère, J P; Labouré, A M; Briat, J F

1990-01-01

Pea seed ferritin is able to incorporate ferrous iron into the mineral core. Fe2+ may be formed by reduction of exogenous Fe3+ with ascorbate or by photoreduction by ferritin and by ferric citrate. In our experimental conditions the bulk of the photoreduction is carried out by ferritin, which is able to photoreduce its endogenous iron. Citrate does not enhance the photoreduction capacity of ferritin, and exogenous ferric citrate improves the yield of the reaction by about 30%. The mineral core of the ferritin is shown to photoreduce actively, and the protein shell does not participate directly in the photoreduction. Low light intensities and low concentration of reducing agents do not allow a release of iron from ferritins, but induce a 'redox mill' of photoreduction and simultaneous ferroxidase-mediated incorporation. High ascorbate concentrations induce the release of ferritin iron. These reactions are accompanied by the correlated occurrence of damage caused by radicals arising from Fenton reactions, leading to specific cleavages in the 28 kDa phytoferritin subunit. This damage caused by radicals occurs during the oxidative incorporation into the mineral core and is prevented by o-phenanthroline or by keeping the samples in the dark. Images Fig. 1. Fig. 2. Fig. 3. Fig. 5. PMID:2375759

Presence of Serum Ferritin before and after Bariatric Surgery: Analysis in Dentate and Edentulous Patients

PubMed Central

Mosquim, Victor; Sales Peres, Matheus de Carvalho; Ceneviva, Reginaldo; Chaim, Elinton Adami

2016-01-01

Society has changed its own lifestyle, specially its eating habits and physical activities, leading to excessive weight and a sedentary behavior, which has contributed to obesity increase. Bariatric surgery is the most effective treatment to obesity, allowing weight loss and its maintenance. However, it has been related high levels of iron deficiency after surgery. A person’s nutritional status might be affected by total or partial tooth loss. The aim of this longitudinal prospective cohort study was to evaluate the levels of serum ferritin before and after bariatric surgery and to identify if there is a relation with tooth loss. The sample was composed of 50 patients selected and assisted at Amaral Carvalho Hospital, located in Jaú city, Brazil. The use and necessity of prosthesis, dental absence or presence, and serum ferritin dosage were evaluated. Student’s t test, Univariate analysis, Chi-square and Odds Ratio were adopted (p<0.05). There was no significant difference regarding the serum ferritin levels between dentate and edentulous patients prior to surgery (p = 0.436). After surgery, the serum ferritin levels were higher in edentulous patients (prosthesis users) when compared to the pre-surgical levels, and the post-surgical levels presented significant difference regarding the dentate patients (p = 0.024). It can be concluded that rehabilitated patients in postoperative period showed better levels of serum ferritin after surgical intervention. PMID:27695053

Presence of Serum Ferritin before and after Bariatric Surgery: Analysis in Dentate and Edentulous Patients.

PubMed

Foratori, Gerson Aparecido; Andrade, Francisco Juliherme Pires de; Mosquim, Victor; Sales Peres, Matheus de Carvalho; Ceneviva, Reginaldo; Chaim, Elinton Adami; Sales Peres, Silvia Helena de Carvalho

2016-01-01

Society has changed its own lifestyle, specially its eating habits and physical activities, leading to excessive weight and a sedentary behavior, which has contributed to obesity increase. Bariatric surgery is the most effective treatment to obesity, allowing weight loss and its maintenance. However, it has been related high levels of iron deficiency after surgery. A person's nutritional status might be affected by total or partial tooth loss. The aim of this longitudinal prospective cohort study was to evaluate the levels of serum ferritin before and after bariatric surgery and to identify if there is a relation with tooth loss. The sample was composed of 50 patients selected and assisted at Amaral Carvalho Hospital, located in Jaú city, Brazil. The use and necessity of prosthesis, dental absence or presence, and serum ferritin dosage were evaluated. Student's t test, Univariate analysis, Chi-square and Odds Ratio were adopted (p<0.05). There was no significant difference regarding the serum ferritin levels between dentate and edentulous patients prior to surgery (p = 0.436). After surgery, the serum ferritin levels were higher in edentulous patients (prosthesis users) when compared to the pre-surgical levels, and the post-surgical levels presented significant difference regarding the dentate patients (p = 0.024). It can be concluded that rehabilitated patients in postoperative period showed better levels of serum ferritin after surgical intervention.

Maxi- and mini-ferritins: minerals and protein nanocages.

PubMed

Bevers, Loes E; Theil, Elizabeth C

2011-01-01

Ferritins synthesize ferric oxide biominerals and are central to all life for concentrating iron and protection against oxidative stress from the ferrous and oxidant chemistry. The ferritin protein nanocages and biomineral synthesis are discussed in terms of wide biological distribution of the maxi-ferritins (24 subunit ± heme) and mini-ferritins (Dps) (12 subunit), conservations of the iron/oxygen catalytic sites in the protein cages, mineral formation (step i. Fe(II) entry and binding, step ii. O(2) or H(2)O(2) binding and formation of transition intermediates, step iii. release of differric oxo mineral precursors from active sites, step iv. nucleation and mineralization) properties of the minerals, and protein control of mineral dissolution and release of Fe(II). Pores in ferritin protein cages control iron entry for mineralization and iron exit after mineral dissolution. The relationship between phosphate or the presence of catalytically inactive subunits (animal L subunits) and ferritin iron mineral disorder is developed based on new information about contributions of ferritin protein cage structure to nucleation in protein cage subunit channels that exit close enough to those of other subunits and exiting mineral nuclei to facilitate bulk mineral formation. How and where protons move in and out of the protein during mineral synthesis and dissolution, how ferritin cage assembly with 12 or 24 subunits is encoded in the widely divergent ferritin amino acid sequences, and what is the role of the protein in synthesis of the bulk mineral are all described as problems requiring new approaches in future investigations of ferritin biominerals.

Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants.

PubMed

Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

2016-01-01

Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the

Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women

PubMed Central

Ali, M. Aktar; Akhmedkhanov, Arslan; Zeleniuch-Jaquotte, Anne; Toniolo, Paolo; Frenkel, Krystyna; Huang, Xi

2010-01-01

Reliability of serum levels of iron, ferritin and nitrite (NO2−) over a 2-year period were evaluated in 40 healthy women (20 pre-menopausal and 20 post-menopausal), ages 39–65 years, from the New York University Women’s Health Study (NYUWHS). Three blood samples per woman collected at yearly intervals were analyzed. Reliability coefficients (RCs) of serum iron, ferritin, and nitrite were 0.03 (95% confidence interval (CI), 0–0.33), 0.90 (95% CI, 0.79–0.95), and 0.72 (95% CI, 0.50–0.86), respectively, for pre-menopausal women, and 0.26 (95% CI, 0–0.56), 0.77 (95% CI, 0.59–0.89), and 0.55 (95% CI, 0.30–0.77), respectively, for post-menopausal women. In a case–control study nested within NYUWHS cohort, serum levels of nitrite, ferritin, and iron were measured in women apparently healthy at the time of blood donation but diagnosed with renal cancer 1.8–12.2 years later (n = 24) and in individually matched controls (two per case). The results suggest that high serum levels of ferritin and nitrite may be associated with a decreased risk of renal cancer (odds ratio (OR), 0.55, 95% CI, 0.15–2.01 for ferritin, and OR, 0.52, 95% CI, 0.17–1.60 for nitrite in women with above median level as compared to women with below median level). The possible role of ferritin and nitrite in renal cancer is discussed. PMID:12670522

Ferritin in hypertensive and diabetic women before and after bariatric surgery.

PubMed

Marin, Flávia Andréia; Rasera Junior, Irineu; Leite, Celso Vieira De Souza; Oliveira, Maria Rita Marques de

2014-10-16

In addition to its important role as marker of iron stores, serum ferritin is a marker of systemic inflammation, and obesity has been associated with chronic inflammation. To verify, six months after surgery, the effect of bariatric surgery on the serum ferritin of women who were hypertensive, diabetic, or comorbidity free before surgery. This retrospective study included 200 women aged 20 to 45 years, with a body mass index (BMI) equal to or greater than 35 kg/m2, submitted to Roux-en-Y gastric bypass (RYGB). Seventy of these women were hypertensive, forty had type 2 diabetes (T2D), and ninety were comorbidity free (CF). They were assessed before and six months after surgery. Anthropometric, laboratory (serum ferritin and hemoglobin), and comorbidity- related data were collected from their medical records. Before surgery, women with comorbidities were older, the hypertensives had higher BMI, and the diabetics had higher serum ferritin levels than the CF women. The study comorbidities had resolved in 68% of the hypertensive women and 86% of the diabetic women six months after RYGB. Also at this time, the serum ferritin of hypertensive women decreased from 110.1±86.3 to 88.7±80.5 ng/dL and of diabetic women, from 164.8±133.4 to 101.2±97.7 ng/dL (p0.05). High ferritin in premenopausal obese women was associated with the main obesity-related comorbidities, and these comorbidities determined the reduction of serum ferritin after bariatric surgery. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Is His54 a gating residue for the ferritin ferroxidase site?

PubMed

Bernacchioni, Caterina; Ciambellotti, Silvia; Theil, Elizabeth C; Turano, Paola

2015-09-01

Ferritin is a ubiquitous iron concentrating nanocage protein that functions through the enzymatic oxidation of ferrous iron and the reversible synthesis of a caged ferric-oxo biomineral. Among vertebrate ferritins, the bullfrog M homopolymer ferritin is a frequent model for analyzing the role of specific amino acids in the enzymatic reaction and translocation of iron species within the protein cage. X-ray crystal structures of ferritin in the presence of metal ions have revealed His54 binding to iron(II) and other divalent cations, with its imidazole ring proposed as "gate" that influences iron movement to/from the active site. To investigate its role, His54 was mutated to Ala. The H54A ferritin variant was expressed and its reactivity studied via UV-vis stopped-flow kinetics. The H54A variant exhibited a 20% increase in the initial reaction rate of formation of ferric products with 2 or 4 Fe²⁺/subunit and higher than 200% with 20 Fe²⁺/subunit. The possible meaning of the increased efficiency of the ferritin reaction induced by this mutation is proposed taking advantage of the comparative sequence analysis of other ferritins. The data here reported are consistent with a role for His54 as a metal ion trap that maintains the correct levels of access of iron to the active site. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Ferritin iron minerals are chelator targets, antioxidants, and coated, dietary iron.

PubMed

Theil, Elizabeth C

2010-08-01

Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley's Anemia and other iron overload conditions are faster removal of ferritin iron with chelators guided to ferritin gated pores by peptides; more ferritin protein synthesis using ferritin mRNA activators, by metal complexes that target mRNA 3D structures; and determining if endocytotic absorption of iron from legumes, which is mostly ferritin, is regulated during iron overload to prevent excess iron entry while providing protein. More of a focus on ferritin features, including protein cage structure, iron mineral, regulatable mRNA, and specific gut absorption properties, will achieve the three novel experimental goals for managing iron homeostasis with transfusion therapies.

Ferritin-Templated Quantum-Dots for Quantum Logic Gates

NASA Technical Reports Server (NTRS)

Choi, Sang H.; Kim, Jae-Woo; Chu, Sang-Hyon; Park, Yeonjoon; King, Glen C.; Lillehei, Peter T.; Kim, Seon-Jeong; Elliott, James R.

2005-01-01

Quantum logic gates (QLGs) or other logic systems are based on quantum-dots (QD) with a stringent requirement of size uniformity. The QD are widely known building units for QLGs. The size control of QD is a critical issue in quantum-dot fabrication. The work presented here offers a new method to develop quantum-dots using a bio-template, called ferritin, that ensures QD production in uniform size of nano-scale proportion. The bio-template for uniform yield of QD is based on a ferritin protein that allows reconstitution of core material through the reduction and chelation processes. One of the biggest challenges for developing QLG is the requirement of ordered and uniform size of QD for arrays on a substrate with nanometer precision. The QD development by bio-template includes the electrochemical/chemical reconsitution of ferritins with different core materials, such as iron, cobalt, manganese, platinum, and nickel. The other bio-template method used in our laboratory is dendrimers, precisely defined chemical structures. With ferritin-templated QD, we fabricated the heptagonshaped patterned array via direct nano manipulation of the ferritin molecules with a tip of atomic force microscope (AFM). We also designed various nanofabrication methods of QD arrays using a wide range manipulation techniques. The precise control of the ferritin-templated QD for a patterned arrangement are offered by various methods, such as a site-specific immobilization of thiolated ferritins through local oxidation using the AFM tip, ferritin arrays induced by gold nanoparticle manipulation, thiolated ferritin positioning by shaving method, etc. In the signal measurements, the current-voltage curve is obtained by measuring the current through the ferritin, between the tip and the substrate for potential sweeping or at constant potential. The measured resistance near zero bias was 1.8 teraohm for single holoferritin and 5.7 teraohm for single apoferritin, respectively.

Enrichment and characterization of ferritin for nanomaterial applications

NASA Astrophysics Data System (ADS)

Ghirlando, Rodolfo; Mutskova, Radina; Schwartz, Chad

2016-01-01

Ferritin is a ubiquitous iron storage protein utilized as a nanomaterial for labeling biomolecules and nanoparticle construction. Commercially available preparations of horse spleen ferritin, widely used as a starting material, contain a distribution of ferritins with different iron loads. We describe a detailed approach to the enrichment of differentially loaded ferritin molecules by common biophysical techniques such as size exclusion chromatography and preparative ultracentrifugation, and characterize these preparations by dynamic light scattering, and analytical ultracentrifugation. We demonstrate a combination of methods to standardize an approach for determining the chemical load of nearly any particle, including nanoparticles and metal colloids. Purification and characterization of iron content in monodisperse ferritin species is particularly critical for several applications in nanomaterial science.

Ferritin gene transcription is regulated by iron in soybean cell cultures.

PubMed

Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

1991-09-15

Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron.

Ferritin gene transcription is regulated by iron in soybean cell cultures.

PubMed Central

Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

1991-01-01

Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron. Images PMID:1896472

Serum ferritin and vitamin d in female hair loss: do they play a role?

PubMed

Rasheed, H; Mahgoub, D; Hegazy, R; El-Komy, M; Abdel Hay, R; Hamid, M A; Hamdy, E

2013-01-01

Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D2 levels were determined for each participant. Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D2 levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. Low serum ferritin and vitamin D2 are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease. Copyright © 2013 S. Karger AG, Basel.

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5340 Ferritin immunological test system. (a) Identification. A ferritin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340...

Energetics of surface confined ferritin during iron loading.

PubMed

Federici, Stefania; Padovani, Francesco; Poli, Maura; Rodriguez, Fernando Carmona; Arosio, Paolo; Depero, Laura E; Bergese, Paolo

2016-09-01

We report on the first quantitative picture on how iron loading inside ferritin molecules occurs when they are self-assembled onto solid surfaces. Recombinant human ferritin H-chain with ferroxidase activity was adsorbed onto microcantilever beams to form a stable close-packed thin film. The obtained nanomechanical system was used to track in real time the energetics of inter-ferritin surface interactions during incubation with Fe(II) for iron loading. We observed that iron loading is accompanied by increasing attractive in-plane inter-ferritin interactions able to perform a maximum surface work of 6.0±1.5mJ/m(2), corresponding to a surface energy variation per ferritin of about 40kbT. Unique to this protein surface transformation, part of the surface work is exerted by the attractive electrostatic forces arising among the new born nanosized iron cores inside the ferritin shells. The remaining work comes from subtle action of steric, bridging and depletion forces. These findings are of fundamental interest and add important information for the rational development of ferritin nanotechnology. Copyright © 2016 Elsevier B.V. All rights reserved.

Enzyme Encapsulation by a Ferritin Cage.

PubMed

Tetter, Stephan; Hilvert, Donald

2017-11-20

Ferritins, conserved across all kingdoms of life, are protein nanocages that evolved to mineralize iron. The last several decades have shown that these cages have considerable technological and medical potential owing to their stability and tolerance to modification, as well as their ability to template nanoparticle synthesis and incorporate small molecules. Here we show that it is possible to encapsulate proteins in a ferritin cage by exploiting electrostatic interactions with its negatively charged interior. Positively supercharged green fluorescent protein is efficiently taken up by Archaeoglobus fulgidus ferritin in a tunable fashion. Moreover, several enzymes were readily incorporated when genetically tethered to this fluorescent protein. These fusion proteins retained high catalytic activity and showed increased tolerance to proteolysis and heat. Equipping ferritins with enzymatic activity paves the way for many new nanotechnological and pharmacological applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serum Ferritin Levels Are Lower in Children With Tic Disorders Compared with Children Without Tics: A Cross-Sectional Study.

PubMed

Avrahami, Matan; Barzilay, Ran; HarGil, Miki; Weizman, Abraham; Watemberg, Nathan

2017-03-01

Alteration in peripheral iron indices has been reported in a number of movement disorders, particularly Parkinson's disease. We hypothesized that iron stores may be diminished in children at an early stage of tic disorder. Using data retrieved from electronic medical records, we compared serum ferritin levels, an indicator of body iron store balance, in drug-naive children diagnosed for the first time with tic disorder (study group; N = 47, 32 boys/15 girls, aged 8.66 ± 3.17 years) compared to age- and sex-matched children with headaches (comparison group, n = 100, 62 boys/38 girls, aged 9.51 ± 3.15 years) treated in the same pediatric neurological clinic. Mean serum ferritin levels were significantly lower (-32%, p = 0.01) in the tic disorder group compared to the headache group. No significant differences were detected in circulatory hemoglobin, iron, transferrin, and platelet count between the two groups. Our findings suggest that body iron stores may be reduced in children with recent-onset tic disorder.

Limitations of serum ferritin to predict liver iron concentration responses to deferasirox therapy in patients with transfusion-dependent thalassaemia.

PubMed

Porter, John B; Elalfy, Mohsen; Taher, Ali; Aydinok, Yesim; Lee, Szu-Hee; Sutcharitchan, Pranee; El-Ali, Ali; Han, Jackie; El-Beshlawy, Amal

2017-03-01

In transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. This post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox. Serum ferritin responses (decreases) occurred in 73% of patients, 80% of whom also have decreased LIC. However, 52% of patients without a serum ferritin response did decrease LIC and by >1 mg Fe/g dw (median 3.9) in 77% of cases. Absolute serum ferritin and LIC values correlated significantly only when serum ferritin was <4000 ng/mL (r = 0.59; P < 0.0001) and not at higher levels (≥4000 ng/mL; r = 0.19). Serum ferritin response was accompanied by decreased LIC in 89% and 70% of cases when serum ferritin was <4000 or ≥4000 ng/mL, respectively. As serum ferritin non-response was associated with LIC decrease in over half of patients, use of liver MRI may be particularly useful for differentiating true from apparent non-responders to deferasirox based on serum ferritin trends alone. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

Ferritin family proteins and their use in bionanotechnology

PubMed Central

He, Didi; Marles-Wright, Jon

2015-01-01

Ferritin family proteins are found in all kingdoms of life and act to store iron within a protein cage and to protect the cell from oxidative damage caused by the Fenton reaction. The structural and biochemical features of the ferritins have been widely exploited in bionanotechnology applications: from the production of metal nanoparticles; as templates for semi-conductor production; and as scaffolds for vaccine design and drug delivery. In this review we first discuss the structural properties of the main ferritin family proteins, and describe how their organisation specifies their functions. Second, we describe materials science applications of ferritins that rely on their ability to sequester metal within their cavities. Finally, we explore the use of ferritin as a container for drug delivery and as a scaffold for the production of vaccines. PMID:25573765

Cross sectional, comparative study of serum erythropoietin, transferrin receptor, ferritin levels and other hematological indices in normal pregnancies and iron deficiency anemia during pregnancy.

PubMed

Sharma, Jai B; Bumma, Sirisha D; Saxena, Renu; Kumar, Sunesh; Roy, Kallol K; Singh, Neeta; Vanamail, P

2016-08-01

To test the correlation of the serum erythropoietin levels, serum transferrrin receptor levels and serum ferritin levels along with other hematological parameters in normal pregnant and anemic pregnant patients. In a prospective study, 120 pregnant women were recruited between 18 and 36 weeks of gestation; 53 normal pregnant patients, 67 anemic pregnant patients, in which, 17 had mild, 30 had moderate anemia, 20 had severe anemia. A blood sample was taken. The various hematological parameters, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), total iron binding capacity (TIBC), serum ferritin, percentage saturation of iron, serum erythropoietin (SEPO) levels, serum transferrin receptors (STfRS) were performed. For statistics, Student's 't' test, Pearson's Chi test, Mann Whitney test and Bartlett test were used as per data. MCV was significantly reduced in anemic pregnancies as compared to non-anemic pregnancies (80.2±9.6 vs 94.12±9.8fl, p=0.001), MCHC was also reduced in them (30.2±3.38% vs 34.2±2.33%, p=0.176), TIBC was significantly increased in anemic pregnancies (343.31±28.54% vs 322.88±23.84%, p=0.001), serum ferritin was significantly reduced (24.9±10.48μg/L vs 31.03±9.98μg/L, p=0.001), percentage saturation of iron was also reduced (53.85±13.21% vs 62.04±15.79%, p=0.0024), serum erythropoietin levels were significantly higher in anemic women (26.24±26.61mU/ml vs 18.12±19.08mU/ml, p=0.064). The levels were significantly higher in severe anemia (46.5±46.8mU/ml than in moderate anemia 27.4±28.1mU/ml and mild anemia 22.8±22.8mU/ml. Serum transferrin receptors were significantly higher in anemic pregnancies than in non-anemic pregnancies (1.40±0.0802μg/ml vs 1.08±0.641μg/ml, p=0.019) with rise being higher in severe anemia (2.28±0.986μg/ml) than in moderate (1.4±0.816μg/ml) and mild anemia (1.16±0.702μg/ml). Various hematological parameters especially sTfR, serum erythropoietin, serum

Thermophilic Ferritin: Versatile Nanohost

NASA Astrophysics Data System (ADS)

Pulsipher, Katherine W.

Thermophilic ferritin from Archaeoglobus fulgidus (AfFtn) is a 24meric, hollow, cage-like protein, whose native function is the oxidation, mineralization, and storage of iron. Unique among ferritins, its self-assembly is dependent on high ionic strength, reflecting the deep sea thermal vent environment where A. fulgidus is found. This ionic strength dependence can be used to encapsulate charged cargo within the AfFtn cavity. Its subunits self-assemble into tetrahedral symmetry, resulting in four, large (4.5 nm), triangular pores, not found in other ferritins. Due to its size (12 nm outer diameter, 8 nm inner diameter), self-assembly properties, and potential for both genetic and chemical modification, AfFtn is an ideal nanocontainer for a variety of cargo, including inorganic nanoparticles and proteins. We have sought to better understand the self-assembly of AfFtn and its encapsulation of various cargo. Guided by computational analysis and through mutagenesis, we have investigated the role of electrostatics along the AfFtn trimeric interface in self-assembly. We have developed a series of single point mutants with increasingly favorable cage assembly. One specific mutation, E65R, has a dramatic effect on AfFtn, almost entirely preventing disassembly and enhancing thermal stability by 14°C. By using a novel graphene-based microelectrode, we have determined that AfFtn maintains its quaternary structure upon encapsulation of a gold nanoparticle, developing a new tool for investigating protein-nanomaterial interactions. We have also shown that AfFtn can be used to template seeded gold nanoparticle growth and have explored two often neglected factors in ferritin-nanoparticle templating: the charge of the gold salt used, and the size of the protein pores. Our results demonstrate that the open, porous structure of AfFtn allows more efficient particle growth than typical closed-pore ferritins. Finally, we have expanded the cargo uptake of AfFtn beyond nanoparticles to

Electrochemically Controlled Reconstitution of Immobilized Ferritins for Bioelectronic Applications

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; Chu, Sang-Hong; King, Glen C.; Watt, Gerald D.

2007-01-01

Site-specific reconstituted nanoparticles were fabricated via electrochemically-controlled biomineralization through the immobilization of biomolecules. The work reported herein includes the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritins with different inorganic cores, and the electrocatalytic reduction of oxygen on the reconstituted Pt-cored ferritins. Protein immobilization on the substrate is achieved by anchoring ferritins with dithiobis-N-succinimidyl propionate (DTSP). A reconstitution process of site-specific electrochemical biomineralization with a protein cage loads ferritins with different core materials. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. This first demonstration of electrochemically controlled site-specific reconstitution of biomolecules provides a new tool for biomineralization and opens the way to produce the bio-templated nanoparticles by electrochemical control. The nanosized platinum-cored ferritins on gold displayed good catalytic activity for the electrochemical reduction of oxygen, which is applicable to biofuel cell applications. This results in a smaller catalyst loading on the electrodes for fuel cells or other bioelectronic devices.

Iron Oxidation and Core Formation in Recombinant Heteropolymeric Human Ferritins.

PubMed

Mehlenbacher, Matthew; Poli, Maura; Arosio, Paolo; Santambrogio, Paolo; Levi, Sonia; Chasteen, N Dennis; Bou-Abdallah, Fadi

2017-08-01

In animals, the iron storage and detoxification protein, ferritin, is composed of two functionally and genetically distinct subunit types, H (heavy) and L (light), which co-assemble in various ratios with tissue specific distributions to form shell-like protein structures of 24 subunits within which a mineralized iron core is stored. The H-subunit possesses a ferroxidase center (FC) that catalyzes Fe(II) oxidation, whereas the L-subunit does not. To assess the role of the L-subunit in iron oxidation and core formation, two human recombinant heteropolymeric ferritins, designated H-rich and L-rich with ratios of ∼20H:4L and ∼22L:2H, respectively, were employed and compared to the human homopolymeric H-subunit ferritin (HuHF). These heteropolymeric ferritins have a composition similar to the composition of those found in hearts and brains (i.e., H-rich) and in livers and spleens (i.e., L-rich). As for HuHF, iron oxidation in H-rich ferritin was found to proceed with a 2:1 Fe(II):O 2 stoichiometry at an iron level of 2 Fe(II) atoms/H-subunit with the generation of H 2 O 2 . The H 2 O 2 reacted with additional Fe(II) in a 2:1 Fe(II):H 2 O 2 ratio, thus avoiding the production of hydroxyl radical. A μ-1,2-peroxo-diFe(III) intermediate was observed at the FC of H-rich ferritin as for HuHF. Importantly, the H-rich protein regenerated full ferroxidase activity more rapidly than HuHF did and additionally formed larger iron cores, indicating dual roles for the L-subunit in facilitating iron turnover at the FC and in mineralization of the core. The L-rich ferritin, while also facilitating iron oxidation at the FC, additionally promoted oxidation at the mineral surface once the iron binding capacity of the FC was exceeded.

Ferritin nanocontainers that self-direct in synthetic polymer systems

NASA Astrophysics Data System (ADS)

Sengonul, Merih C.

Currently, there are many approaches to introduce functionality into synthetic polymers. Among these, for example, are copolymerization, grafting, and blending methods. However, modifications made by such methods also change the thermodynamics and rheological properties of the polymer system of interest, and each new modification often requires a costly reoptimization of polymer processing. Such a reoptimalization would not be necessary if new functionality could be introduced via a container whose external surface is chemically and physically tuned to interact with the parent polymer. The contents of the container could then be changed without changing other important properties of the parent polymer. In this context this thesis project explores an innovative nanocontainer platform which can be introduced into phase-separating homopolymer blends. Ferritin is a naturally existing nanocontainer that can be used synthetically to package and selectively transport functional moieties to a particular phase that is either in the bulk or on the surface of a homopolymer blend system. The principal focus of this work centers on modifying the surface of wild ferritin to: (1) render modified ferritin soluble in a non-aqueous solvent; and (2) impart it with self-directing properties when exposed to a homopolymer blend surface or incorporated into the bulk of a homopolymer blend. Wild ferritin is water soluble, and this research project successfully modified wild ferritin by grafting either amine-functional poly(ethylene glycol) (PEG) or short-chain alkanes to carbodiimide activated carboxylate groups on ferritin's surface. Such modified ferritin is soluble in dichloromethane (DCM). Modification was confirmed by ion-exchange chromatography, zeta-potential measurements, and electrospray mass spectroscopy. FT-IR was used to quantify the extent of PEGylation of the reaction products through area ratios of the -C-O-C asymmetric stretching vibration of the grafted PEG chains to the

[Polyglobulia and bronchopneumopathies: correlations of ferritin and other ferric parameters with various erythrocytic indexes].

PubMed

Sánchez Sánchez, M L; Ciriza de los Ríos, C; Arroyo Vicente, M; Ortega de Heredia, D; Arroyo Ordóñez, M J; Rubio Pérez, P

1993-08-01

In 15 patients with chronic bronchopneumopathy (7 with polyglobulia and 8 without it), we observed that polyglobulic patients had higher average levels of sideremia and basal saturation of transferrin and lower levels of HCM, CHCM and VCM. No significant differences were observed in the average levels of ferritin between both groups. Overall, in this series of 15 patients, a significant inverse correlation was observed between sideremia and HCM (r = -0.52; p < 0.05) and between sideremia and CHCM (r = -0.55, p < 0.5), as well as a trend towards a direct correlation between sideremia and the red blood cells count (r = 0.45, N.S.). There was also a direct correlation between serum ferritin and the sedimentation rate (r = 0.72, p < 0.01) and trends towards inverse correlations although not significant, between ferritin and sideremia (r = -0.25, N.S.). These data reflect a hyperconsumption of iron in the respiratory polyglobulia, with some relative deficit, suggesting as well that serum ferritin is not a good enough criteria in these cases for the evaluation of iron deposits, because it behaves like the sedimentation rate with respect to acute phase reactants when there is inflammation.

Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload.

PubMed

Puliyel, Mammen; Sposto, Richard; Berdoukas, Vasilios A; Hofstra, Thomas C; Nord, Anne; Carson, Susan; Wood, John; Coates, Thomas D

2014-04-01

Ferritin levels and trends are widely used to manage iron overload and assess the efficacy of prescribed iron chelation in patients with transfusional iron loading. A retrospective cohort study was conducted in 134 patients with transfusion-dependent anemia, over a period of up to 9 years. To determine whether the trends in ferritin adequately reflect the changes in total body iron, changes in ferritin between consecutive liver iron measurements by magnetic resonance imaging (MRI) were compared to changes in liver iron concentrations (LIC), a measure of total body iron. The time period between two consecutive LIC measurements was defined as a segment. Trends in ferritin were considered to predict the change in LIC within a segment if the change in one parameter was less than twofold that of the other, and was in the same direction. Using the exclusion criteria detailed in methods, the trends in ferritin were compared to changes in LIC in 358 segments. An agreement between ferritin trends and LIC changes was found in only 38% of the 358 segments examined. Furthermore, the change in ferritin was in opposite direction to that of LIC in 26% of the segments. Trends in ferritin were a worse predictor of changes in LIC in sickle cell disease than in thalassemia (P < 0.01). While ferritin is a convenient measure of iron status; ferritin trends were unable to predict changes in LIC in individual patients. Ferritin trends need to be interpreted with caution and confirmed by direct measurement of LIC. Copyright © 2013 Wiley Periodicals, Inc.

New insights into ferritin synthesis and function highlight a link between iron homeostasis and oxidative stress in plants.

PubMed

Briat, Jean-Francois; Ravet, Karl; Arnaud, Nicolas; Duc, Céline; Boucherez, Jossia; Touraine, Brigitte; Cellier, Francoise; Gaymard, Frederic

2010-05-01

Iron is an essential element for both plant productivity and nutritional quality. Improving plant iron content was attempted through genetic engineering of plants overexpressing ferritins. However, both the roles of these proteins in plant physiology, and the mechanisms involved in the regulation of their expression are largely unknown. Although the structure of ferritins is highly conserved between plants and animals, their cellular localization differs. Furthermore, regulation of ferritin gene expression in response to iron excess occurs at the transcriptional level in plants, in contrast to animals which regulate ferritin expression at the translational level. In this review, an overview of our knowledge of bacterial and mammalian ferritin synthesis and functions is presented. Then the following will be reviewed: (a) the specific features of plant ferritins; (b) the regulation of their synthesis during development and in response to various environmental cues; and (c) their function in plant physiology, with special emphasis on the role that both bacterial and plant ferritins play during plant-bacteria interactions. Arabidopsis ferritins are encoded by a small nuclear gene family of four members which are differentially expressed. Recent results obtained by using this model plant enabled progress to be made in our understanding of the regulation of the synthesis and the in planta function of these various ferritins. Studies on plant ferritin functions and regulation of their synthesis revealed strong links between these proteins and protection against oxidative stress. In contrast, their putative iron-storage function to furnish iron during various development processes is unlikely to be essential. Ferritins, by buffering iron, exert a fine tuning of the quantity of metal required for metabolic purposes, and help plants to cope with adverse situations, the deleterious effects of which would be amplified if no system had evolved to take care of free reactive iron.

Ferritin family proteins and their use in bionanotechnology.

PubMed

He, Didi; Marles-Wright, Jon

2015-12-25

Ferritin family proteins are found in all kingdoms of life and act to store iron within a protein cage and to protect the cell from oxidative damage caused by the Fenton reaction. The structural and biochemical features of the ferritins have been widely exploited in bionanotechnology applications: from the production of metal nanoparticles; as templates for semi-conductor production; and as scaffolds for vaccine design and drug delivery. In this review we first discuss the structural properties of the main ferritin family proteins, and describe how their organisation specifies their functions. Second, we describe materials science applications of ferritins that rely on their ability to sequester metal within their cavities. Finally, we explore the use of ferritin as a container for drug delivery and as a scaffold for the production of vaccines. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Ferritin-based nanocrystals for solar energy harvesting

NASA Astrophysics Data System (ADS)

Colton, John; Erickson, Stephen; Olsen, Cameron; Embley, Jacob; Smith, Trevor; Watt, Richard

2015-03-01

Ferritin is a 12 nm diameter hollow protein with an 8 nm cavity that can be filled with a variety of nanocrystals (ferrihydrite being native). We report on several experiments with ferritin-based nanocrystals designed to utilize ferritin for solar energy harvesting. First, we have shown that the native band gap can be altered by controlling nanocrystal size, by replacing the native iron oxide core with other metal oxides, and by depositing halides and oxo-anions with the iron oxide core. This gives available band gaps of 1.6 to 2.3 eV. Theoretical efficiency calculations based on these band gaps show that the efficiency of a multi-junction solar cell based on layered structures of ferritin can be as high as 44.9 %, and up to 63.1 % if a ferritin-based material with band gap of 1.1 eV can be developed. For the latter case, the efficiencies remain quite high even in a current-matched configuration, namely 50.0 %. We have also demonstrated that photo-excitation of these materials can produce charge separation and give rise to usable electrons; we have used photo-excited electrons to reduce gold in solution and thereby produce gold nanoparticles on the surface of the ferritin. This technique can potentially be extended to platinum, whose nanoparticles catalyze water splitting. This research was partially supported by the Utah Office of Energy Development, Governor's Energy Leadership Scholars Program.

Self-assembly in the ferritin nano-cage protein superfamily.

PubMed

Zhang, Yu; Orner, Brendan P

2011-01-01

Protein self-assembly, through specific, high affinity, and geometrically constraining protein-protein interactions, can control and lead to complex cellular nano-structures. Establishing an understanding of the underlying principles that govern protein self-assembly is not only essential to appreciate the fundamental biological functions of these structures, but could also provide a basis for their enhancement for nano-material applications. The ferritins are a superfamily of well studied proteins that self-assemble into hollow cage-like structures which are ubiquitously found in both prokaryotes and eukaryotes. Structural studies have revealed that many members of the ferritin family can self-assemble into nano-cages of two types. Maxi-ferritins form hollow spheres with octahedral symmetry composed of twenty-four monomers. Mini-ferritins, on the other hand, are tetrahedrally symmetric, hollow assemblies composed of twelve monomers. This review will focus on the structure of members of the ferritin superfamily, the mechanism of ferritin self-assembly and the structure-function relations of these proteins.

Permanganate-based synthesis of manganese oxide nanoparticles in ferritin

NASA Astrophysics Data System (ADS)

Olsen, Cameron R.; Smith, Trevor J.; Embley, Jacob S.; Maxfield, Jake H.; Hansen, Kameron R.; Peterson, J. Ryan; Henrichsen, Andrew M.; Erickson, Stephen D.; Buck, David C.; Colton, John S.; Watt, Richard K.

2017-05-01

This paper investigates the comproportionation reaction of MnII with {{{{MnO}}}4}- as a route for manganese oxide nanoparticle synthesis in the protein ferritin. We report that {{{{MnO}}}4}- serves as the electron acceptor and reacts with MnII in the presence of apoferritin to form manganese oxide cores inside the protein shell. Manganese loading into ferritin was studied under acidic, neutral, and basic conditions and the ratios of MnII and permanganate were varied at each pH. The manganese-containing ferritin samples were characterized by transmission electron microscopy, UV/Vis absorption, and by measuring the band gap energies for each sample. Manganese cores were deposited inside ferritin under both the acidic and basic conditions. All resulting manganese ferritin samples were found to be indirect band gap materials with band gap energies ranging from 1.01 to 1.34 eV. An increased UV/Vis absorption around 370 nm was observed for samples formed under acidic conditions, suggestive of MnO2 formation inside ferritin.

Ferritin and ferrihydrite nanoparticles as iron sources for Pseudomonas aeruginosa

PubMed Central

Dehner, Carolyn; Morales-Soto, Nydia; Behera, Rabindra K.; Shrout, Joshua; Theil, Elizabeth C.; Maurice, Patricia A.

2013-01-01

Metabolism of iron derived from insoluble and/ or scarce sources is essential for pathogenic and environmental microbes. The ability of Pseudomonas aeruginosa to acquire iron from exogenous ferritin was assessed; ferritin is an iron-concentrating and antioxidant protein complex composed of a catalytic protein and caged ferrihydrite nanomineral synthesized from Fe(II) and O2 or H2O2. Ferritin and free ferrihydrite supported growth of P. aeruginosa with indistinguishable kinetics and final culture densities. The P. aeruginosa PAO1 mutant (ΔpvdDΔpchEF), which is incapable of siderophore production, grew as well as the wild type when ferritin was the iron source. Such data suggest that P. aeruginosa can acquire iron by siderophore-independent mechanisms, including secretion of small-molecule reductant(s). Protease inhibitors abolished the growth of the siderophore-free strain on ferritins, with only a small effect on growth of the wild type; predictably, protease inhibitors had no effect on growth with free ferrihydrite as the iron source. Proteolytic activity was higher with the siderophore-free strain, suggesting that the role of proteases in the degradation of ferritin is particularly important for iron acquisition in the absence of siderophores. The combined results demonstrate the importance of both free ferrihydrite, a natural environmental form of iron and a model for an insoluble form of partly denatured ferritin called hemosiderin, and caged ferritin iron minerals as bacterial iron sources. Ferritin is also revealed as a growth promoter of opportunistic, pathogenic bacteria such a P. aeruginosa in diseased tissues such as the cystic fibrotic lung, where ferritin concentrations are abnormally high. PMID:23417538

Octopus microvasculature: permeability to ferritin and carbon.

PubMed

Browning, J

1979-01-01

The permeability of Octopus microvasculature was investigated by intravascular injection of carbon and ferritin. Vessels were tight to carbon while ferritin penetrated the pericyte junction, and was found extravascularly 1-2 min after its introduction. Vesicles occurred rarely in pericytes; fenestrae were absent. The discontinuous endothelial layer did not consitute a permeability barrier. The basement membrane, although retarding the movement of ferritin, was permeable to it; carbon did not penetrate the basement membrane. Evidence indicated that ferritin, and thus similarly sized and smaller water soluble materials, traverse the pericyte junction as a result of bulk fluid flow. Comparisons are made with the convective (or junctional) and slower, diffusive (or vesicular) passage of materials known to occur across the endothelium of continuous capillaries in mammals. Previous macrophysiological determinations concerning the permeability of Octopus vessels are questioned in view of these findings. Possible reasons for some major structural differences in the microcirculatory systems of cephalopods and vertebrates are briefly discussed.

Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin

NASA Astrophysics Data System (ADS)

Volatron, Jeanne; Kolosnjaj-Tabi, Jelena; Javed, Yasir; Vuong, Quoc Lam; Gossuin, Yves; Neveu, Sophie; Luciani, Nathalie; Hémadi, Miryana; Carn, Florent; Alloyeau, Damien; Gazeau, Florence

2017-01-01

Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein - namely the ferritin - in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products.

Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin

PubMed Central

Volatron, Jeanne; Kolosnjaj-Tabi, Jelena; Javed, Yasir; Vuong, Quoc Lam; Gossuin, Yves; Neveu, Sophie; Luciani, Nathalie; Hémadi, Miryana; Carn, Florent; Alloyeau, Damien; Gazeau, Florence

2017-01-01

Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein – namely the ferritin – in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products. PMID:28067263

Loop electrostatics modulates the intersubunit interactions in ferritin.

PubMed

Bernacchioni, Caterina; Ghini, Veronica; Pozzi, Cecilia; Di Pisa, Flavio; Theil, Elizabeth C; Turano, Paola

2014-11-21

Functional ferritins are 24-mer nanocages that self-assemble with extended contacts between pairs of 4-helix bundle subunits coupled in an antiparallel fashion along the C2 axes. The largest intersubunit interaction surface in the ferritin nanocage involves helices, but contacts also occur between groups of three residues midway in the long, solvent-exposed L-loops of facing subunits. The anchor points between intersubunit L-loop pairs are the salt bridges between the symmetry-related, conserved residues Asp80 and Lys82. The resulting quaternary structure of the cage is highly soluble and thermostable. Substitution of negatively charged Asp80 with a positively charged Lys in homopolymeric M ferritin introduces electrostatic repulsions that inhibit the oligomerization of the ferritin subunits. D80K ferritin was present in inclusion bodies under standard overexpressing conditions in E. coli, contrasting with the wild type protein. Small amounts of fully functional D80K nanocages formed when expression was slowed. The more positively charged surface results in a different solubility profile and D80K crystallized in a crystal form with a low density packing. The 3D structure of D80K variant is the same as wild type except for the side chain orientations of Lys80 and facing Lys82. When three contiguous Lys groups are introduced in D80KI81K ferritin variant the nanocage assembly is further inhibited leading to lower solubility and reduced thermal stability. Here, we demonstrate that the electrostatic pairing at the center of the L-loops has a specific kinetic role in the self-assembly of ferritin nanocages.

The clearance of /sup 131/I-human plasma ferritin in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Worwood, M.; Cragg, S.J.; Williams, A.M.

1982-10-01

Ferritin was purified 33,000-fold from the plasma of patients with idiopathic hemochromatosis. The plasma ferritin was labeled with /sup 131/I and injected into 2 normal men. Clearance was found to be relatively slow, with 50% /sup 131/I-ferritin remaining in the plasma at 27-30 hr. The fraction of plasma ferritin that bound to concanavalin-A was found to be cleared more slowly than the nonbinding fraction. These findings confirm our previous suggestion that glycosylation is a major factor prolonging the survival of ferritin in the plasma, but differ from the results of earlier studies in experimental animals and preterm infants, which indicatedmore » very rapid plasma ferritin turnover.« less

Specific repression of β-globin promoter activity by nuclear ferritin

PubMed Central

Broyles, Robert H.; Belegu, Visar; DeWitt, Christina R.; Shah, Sandeep N.; Stewart, Charles A.; Pye, Quentin N.; Floyd, Robert A.

2001-01-01

Developmental hemoglobin switching involves sequential globin gene activations and repressions that are incompletely understood. Earlier observations, described herein, led us to hypothesize that nuclear ferritin is a repressor of the adult β-globin gene in embryonic erythroid cells. Our data show that a ferritin-family protein in K562 cell nuclear extracts binds specifically to a highly conserved CAGTGC motif in the β-globin promoter at −153 to −148 bp from the cap site, and mutation of the CAGTGC motif reduces binding 20-fold in competition gel-shift assays. Purified human ferritin that is enriched in ferritin-H chains also binds the CAGTGC promoter segment. Expression clones of ferritin-H markedly repress β-globin promoter-driven reporter gene expression in cotransfected CV-1 cells in which the β-promoter has been stimulated with the transcription activator erythroid Krüppel-like factor (EKLF). We have constructed chloramphenicol acetyltransferase reporter plasmids containing either a wild-type or mutant β-globin promoter for the −150 CAGTGC motif and have compared the constructs for susceptibility to repression by ferritin-H in cotransfection assays. We find that stimulation by cotransfected EKLF is retained with the mutant promoter, whereas repression by ferritin-H is lost. Thus, mutation of the −150 CAGTGC motif not only markedly reduces in vitro binding of nuclear ferritin but also abrogates the ability of expressed ferritin-H to repress this promoter in our cell transfection assay, providing a strong link between DNA binding and function, and strong support for our proposal that nuclear ferritin-H is a repressor of the human β-globin gene. Such a repressor could be helpful in treating sickle cell and other genetic diseases. PMID:11481480

Identification and characterization of a receptor for tissue ferritin on activated rat lipocytes.

PubMed Central

Ramm, G A; Britton, R S; O'Neill, R; Bacon, B R

1994-01-01

Hepatic iron overload causes lipocyte activation with resultant fibrogenesis. This study examines whether rat lipocytes express ferritin receptors, which could be involved in paracellular iron movement and in cellular regulation. Lipocytes from normal rat liver were cultured on plastic and incubated with 125I-labeled rat liver ferritin (RLF) +/- a 100-fold excess of either unlabeled RLF or human heart ferritin, human liver ferritin, human recombinant H-ferritin, a mutant human recombinant L-ferritin, or a variety of nonspecific proteins. Specific binding sites for ferritin were demonstrated by displacement of 125I-RLF by RLF (64.5 +/- 4.3%) and by other ferritins (55-60%), but not by recombinant L-ferritin. Scatchard analysis demonstrated a single class of binding sites with a Kd of 5.1 +/- 2.9 x 10(-10) M, maximum binding capacity of 4.7 +/- 1.3 x 10(-12) M, and 5,000-10,000 receptor sites/cell. Ferritin receptor expression was observed only in activated lipocytes. Internalization of RLF was observed within 15 min using FITC-RLF and confocal microscopy. This study demonstrates that (a) activated lipocytes express a specific high affinity ferritin receptor; (b) the binding appears to be dependent on the H-ferritin subunit; and (c) lipocytes internalize ferritin. Expression of ferritin receptors in activated lipocytes suggests that the receptor may either be involved in the activation cascade or may be a marker of activation. Images PMID:8040296

Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent.

PubMed

Hughes, Elizabeth A; Patel, Jeetesh V; Bredow, Zosia; Gill, Paramjit S; Chackathayil, Julia; Agaoglu, Elif S; Flinders, Paul; Mirrielees, Rebecca

2015-01-01

Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P = 0.005), irrespective of site, gender, and central obesity (P ≤ 0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P < 0.001). Diabetes was less in those with low ferritin (<20 mg/mL), P < 0.008, and risk estimate = 0.35 (95% CI 0.15-0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P = 0.001) and age (P < 0.001). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors.

Correlation between PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients.

PubMed

Dragović, Gordana; Sumarac-Dumanovic, Mirjana; Khawla, Al Musalhi; Soldatović, Ivan; Andjić, Mladen; Jevtović, Djordje; Nair, Devaki

2018-06-22

Data about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients' age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = -0.282; p = 0.025). PAI-1 (Rho = 0.334; p = 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α, IL-1 β, IFN �

[The usefulness of evaluation of: ferritin, ultrasensitive CRP and tissue specific polypeptide 18th (TPS) in assessment of therapy efficacy in patients with nasal polyps].

PubMed

Pałac, Jacek; Bratek, Szczepan; Partyka, Robert; Misiołek, Maciej

2014-01-01

Chronic rhinosinusitis with nasal polyps is social, clinical and cost-effective problem, by reason of bothersome symptoms, chronic nature of the disease, tendency to recur and lack of satisfying treatment. The aim of this study is assessment of suitability of hsCRP, ferritin and blood levels in nasal polyps patients in evaluation of treatment efficacy. The study enrolled 38 patients between 20 and 68 years of age. Patients were divided into 2 groups. Levels of ultrasensitive CRP ferritin and TPS have been measured in all patients. The ultrasensitive CRP levels have been measured by chemiluminescence method. Ferritin levels have been measured by MEIA method. The TPS levels have been measured by chemiluminescence method. Comparison of mean ferritin levels in both study groups in each stage of observation shows the significant difference of mean values in only 6 weeks after surgery. Mean ferritin level is significantly lower in group I than in group II (p<0.05). Mean hsCRP levels vary from one corresponding to ferritin levels. Statistically significant difference between study groups in 2nd and 6th week after surgery has been ascertained (p<0.05). Similarly, like in ferritin levels, the TPS levels are significantly different in 6th week after surgery. Analysis of ferritin, hsCRP and TPS serum levels indicates that these may be useful in assessment of treatment efficacy in patients with nasal polyps. Rise of the chosen inflammatory state parameter level in the postoperative monitoring and anti-inflammatory treatment introduction in nasal polyps patients may inhibit the recurrence of the disease. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Characterization of a New Ferritin Protein from the Polychaete Chaetopterus Sp.

NASA Astrophysics Data System (ADS)

Hamlish, N.; Deheyn, D.; De Meulenaere, E.

2016-02-01

The marine polychaete worm Chaetopterus sp. secretes a sticky mucus that exhibits a soft blue long-lasting bioluminescence. Iron (both ferrous and ferric) and riboflavin have been found abundant in the mucus and identified as potential cofactors involved in the control of the light production. The Deheyn lab has recently identified a novel ferritin protein (ChF) from fractions of the worm mucus still able to produce bioluminescence after purification by chromatography. Ferritin proteins are ubiquitous across the animal kingdom and exhibit ferroxidase activity, converting ferrous iron into a ferric form that is stably stored and soluble in the ferritin. Here, ferritin may serve as a source of biological iron for the worm through a process of iron acquisition, storage, and release during the light production process. This study addresses these options by assessing foundational data that characterize the ferroxidase activity of recombinant ChF with respect to human heavy-chain ferritin (HuHF). ChF exhibits faster initial rates of iron oxidation than HuHF, but reaches an equilibrium state with detectable levels of ferrous iron still in solution; in contrast this was was not observed for HuHF that oxidizes all available iron in solution. This may support the hypothesis that ChF has a reducing activity. This could involve the release of ferric iron, which may be reduced by flavin molecules found in the mucus; the resulting ferrous iron could then subsequently undergo a Fenton reaction, acting as a source of electrons for long-lasting mucus bioluminescence. Word Count: 240

Construction of a cDNA library for sea cucumber Acaudina leucoprocta and differential expression of ferritin peptide

NASA Astrophysics Data System (ADS)

Zhou, Jun; Hou, Fujing; Li, Ye; Su, Xiurong; Li, Taiwu; Jin, Chunhua

2016-07-01

Acaudina leucoprocta is an edible sea cucumber of economic interest that is widely distributed in China. Little information is available concerning the molecular genetics of this species although such knowledge would contribute to a better understanding of the optimal conditions for its aquaculture and its mechanisms of defense against disease. Therefore, we constructed a cDNA library and, based on bioinformatics analysis of the sequences, the functions of 75% of the cDNAs were identified, including those involved in cell structure, energy metabolism, mitochondrial function, and signal transduction pathways. Approximately 25% of genes in the library were unmatched. The gene for A. leucoprocta ferritin was also cloned. The predicted amino-acid sequence of ferritin displayed significant homology with other sea-cucumber counterparts but indicated that it was a new member of the ferritin family. Semiquantitative real-time RT-PCR indicated the highest levels of ferritin mRNA expression in the intestine. A polyclonal antibody of ferritin was also produced. These data provide a set of molecular tools essential for further studies of the functions of ferritin protein in A. leucoprocta.

Menopause increases the iron storage protein ferritin in skin.

PubMed

Pelle, Edward; Jian, Jinlong; Zhang, Qi; Muizzuddin, Neelam; Yang, Qing; Dai, Jisen; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna; Huang, Xi

2013-01-01

Menstruation and desquamation are important routes for humans to excrete iron. Because menstruation is no longer available in postmenopausal women, in the present study, we examined whether iron accumulates more in postmenopausal skin than in premenopausal skin. Skin biopsy samples were obtained from six pre- and six postmenopausal Caucasian women. Iron levels in the form of ferritin were 42% higher, but vascular endothelial growth factor and total antioxidant capacity were 45% and 34% lower in postmenopausal skin (58.8 ± 1.3 years old) than in premenopausal skin (41.6 ± 1.7 years old), respectively. Moreover, in vitro cultured normal human epidermal keratinocytes had surprisingly high levels of ferritin when compared to immortalized human breast epithelial MCF-10A cells or human liver HepG2 cancer cells. Our results indicate that skin is a cellular repository of iron and that menopause increases iron in skin and, thus, may contribute to the manifestation of accelerated skin aging and photo aging after menopause.

First comparative characterization of three distinct ferritin subunits from a teleost: Evidence for immune-responsive mRNA expression and iron depriving activity of seahorse (Hippocampus abdominalis) ferritins.

PubMed

Oh, Minyoung; Umasuthan, Navaneethaiyer; Elvitigala, Don Anushka Sandaruwan; Wan, Qiang; Jo, Eunyoung; Ko, Jiyeon; Noh, Gyeong Eon; Shin, Sangok; Rho, Sum; Lee, Jehee

2016-02-01

Ferritins play an indispensable role in iron homeostasis through their iron-withholding function in living beings. In the current study, cDNA sequences of three distinct ferritin subunits, including a ferritin H, a ferritin M, and a ferritin L, were identified from big belly seahorse, Hippocampus abdominalis, and molecularly characterized. Complete coding sequences (CDS) of seahorse ferritin H (HaFerH), ferritin M (HaFerM), and ferritin L (HaFerL) subunits were comprised of 531, 528, and 522 base pairs (bp), respectively, which encode polypeptides of 177, 176, and 174 amino acids, respectively, with molecular masses of ∼20-21 kDa. Our in silico analyses demonstrate that these three ferritin subunits exhibit the typical characteristics of ferritin superfamily members including iron regulatory elements, domain signatures, and reactive centers. The coding sequences of HaFerH, M, and L were cloned and the corresponding proteins were overexpressed in a bacterial system. Recombinantly expressed HaFer proteins demonstrated detectable in vivo iron sequestrating (ferroxidase) activity, consistent with their putative iron binding capability. Quantification of the basal expression of these three HaFer sequences in selected tissues demonstrated a gene-specific ubiquitous spatial distribution pattern, with abundance of mRNA in HaFerM in the liver and predominant expression of HaFerH and HaFerL in blood. Interestingly, the basal expression of all three ferritin genes was found to be significantly modulated against pathogenic stress mounted by lipopolysaccharides (LPS), poly I:C, Streptococcus iniae, and Edwardsiella tarda. Collectively, our findings suggest that the three HaFer subunits may be involved in iron (II) homeostasis in big belly seahorse and that they are important in its host defense mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantification of ferritin bound iron in human serum using species-specific isotope dilution mass spectrometry.

PubMed

Ren, Yao; Walczyk, Thomas

2014-09-01

Ferritin is a hollow sphere protein composed of 24 subunits that can store up to 4500 iron atoms in its inner cavity. It is mainly found in the liver and spleen but also in serum at trace levels. Serum ferritin is considered as the best single indicator in assessing body iron stores except liver or bone marrow biopsy. However, it is confounded by other disease conditions. Ferritin bound iron (FBI) and ferritin saturation have been suggested as more robust biomarkers. The current techniques for FBI determination are limited by low antibody specificity, low instrument sensitivity and possible analyte losses during sample preparation. The need for a highly sensitive and reliable method is widely recognized. Here we describe a novel technique to detect serum FBI using species-specific isotope dilution mass spectrometry (SS-IDMS). [(57)Fe]-ferritin was produced by biosynthesis and in vitro labeling with the (57)Fe spike in the form of [(57)Fe]-citrate after cell lysis and heat treatment. [(57)Fe]-ferritin for sample spiking was further purified by fast liquid protein chromatography. Serum ferritin and added [(57)Fe]-ferritin were separated from other iron species by ultrafiltration followed by isotopic analysis of FBI using negative thermal ionization mass spectrometry. Repeatability of our assay is 8% with an absolute detection limit of 18 ng FBI in the sample. As compared to other speciation techniques, SS-IDMS offers maximum control over sample losses and species conversion during analysis. The described technique may therefore serve as a reference technique for clinical applications of FBI as a new biomarker for assessing body iron status.

Efficacy and safety of deferasirox estimated by serum ferritin and labile plasma iron levels in patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia with transfusional iron overload.

PubMed

Kim, Il-Hwan; Moon, Joon-Ho; Lim, Sung-Nam; Sohn, Sang-Kyun; Kim, Hoon-Gu; Lee, Gyeong-Won; Kim, Yang-Soo; Lee, Ho-Sup; Kwon, Ki-Young; Kim, Sung-Hyun; Park, Kyung-Tae; Chung, Joo-Seop; Lee, Won-Sik; Lee, Sang-Min; Hyun, Myung-Soo; Kim, Hawk; Ryoo, Hun-Mo; Bae, Sung-Hwa; Joo, Young-Don

2015-07-01

Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality. This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled. Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was -65 ng/mL in AA (p = 0.037), -647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and -552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was -0.17 μmol/L in AA, -0.21 μmol/L in MDS-LR, and -0.30 μmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%). DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups. © 2015 AABB.

Iron Oxide Biominerals in Protein Nanocages, the Ferritins: Easing Into Life With Oxygen?

NASA Astrophysics Data System (ADS)

Theil, E. C.

2008-12-01

Organisms with ferritins could represent the progenitors of organisms that successfully made the transition to aerobic life. Ferritins are protein nanocages (8 or 12 nm diameter) that catalyze reactions between Fe(II) and O2 or H2O2 to synthesize ferrihydrite-like biominerals of Fe2O3(H2 O)n; phosphate is sometimes incorporated during mineralization. All groups of organisms, archea, bacteria, plants and animals have ferritins. Catalytic reactions between Fe and O occur in the protein cage with the products moving into the central protein cavity (5 or 8 nm diameter) where mineralization occurs; mineral sizes reach 4500 Fe with more than 7000 O atoms in the large cavities of maxi-ferritins and 500 Fe with more than 800 O atoms in the smaller, mini-ferritins, also called Dps proteins. H2O2 is preferentially used by mini-ferritins in archea and bacteria, contrasting with O2, preferentially used by maxi-ferritins in bacteria plants and animals, and some bacterial mini-ferritins that use either H2O2 or O2, to oxidize Fe(II) during biomineralization. The study of ferritins in contemporary organisms can illuminate mechanisms for oxygen and oxidant responses in changing environments now and in the past. Multiple genes encoding ferritins are often regulated by different environmental stimuli and in multi-cellular organisms, by tissue-specific, differentiation programs. The single celled E.coli has four ferritin genes, encoding three maxi-ferritins, one with a heme cofactor (bacterioferritin), and one mini-ferritin (Dps), expressed at different points in the culture cycle and/or in response to different stresses. Environmental iron, oxygen and peroxide all change the amounts of ferritin. When iron is plentiful, mineralized ferritin accumulates. Ferritin iron is recovered during periods of iron deficiency, apparently by selective unfolding of gated pores in ferritin protein nanocage that expose the mineral to reductants. Gene (DNA) transcription is the genetic target for iron

Ferritin, an iron source in meat for Staphylococcus xylosus?

PubMed

Vermassen, Aurore; Talon, Régine; Leroy, Sabine

2016-05-16

Staphylococcus xylosus is frequently isolated from food of animal origin. Moreover, this species is one of the major starter cultures used for meat fermentation. Iron is a key element for growth and survival of bacteria. Meat is particularly rich in haemic (myoglobin and haemoglobin) and non-haemic (ferritin and transferrin) iron sources. Ferritin is a storage protein able to capture large quantities of iron. It is highly resistant to microbial attack and few microorganisms can use it as an iron source. Surprisingly, we found that the S. xylosus C2a strain grows in the presence of ferritin as a sole iron source. A three-cistron operon was highly overexpressed under ferritin iron growth conditions. We generated a deletion-insertion in the first gene of the operon and evaluated the phenotype of the mutant. The mutant showed decreased growth because it was less able to acquire iron from ferritin. Transcriptional analysis of the mutant revealed downregulation of several genes involved in the response to oxidative stress. This study characterized for the first time the capacity of a Staphylococcus to use iron from ferritin and revealed that a potential reductive pathway was involved in this acquisition. We hypothesize that this ability could give an advantage to S. xylosus in meat products. Copyright © 2016 Elsevier B.V. All rights reserved.

Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

PubMed

Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

2014-03-01

Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Incorporation of organometallic Ru complexes into apo-ferritin cage.

PubMed

Takezawa, Yusuke; Böckmann, Philipp; Sugi, Naoki; Wang, Ziyue; Abe, Satoshi; Murakami, Tatsuya; Hikage, Tatsuo; Erker, Gerhard; Watanabe, Yoshihito; Kitagawa, Susumu; Ueno, Takafumi

2011-03-14

Spherical protein cages such as an iron storage protein, ferritin, have great potential as nanometer-scale capsules to assemble and store metal ions and complexes. We report herein the synthesis of a composite of an apo-ferritin cage and Ru(p-cymene) complexes. Ru complexes were efficiently incorporated into the ferritin cavity without degradation of its cage structure. X-Ray crystallography revealed that the Ru complexes were immobilized on the interior surface of the cage mainly by the coordination of histidine residues.

Erythropoiesis-stimulating agent dosing, haemoglobin and ferritin levels in UK haemodialysis patients 2005-13.

PubMed

Birnie, Kate; Caskey, Fergus; Ben-Shlomo, Yoav; Sterne, Jonathan A C; Gilg, Julie; Nitsch, Dorothea; Tomson, Charles

2017-04-01

Erythropoiesis-stimulating agents (ESAs) with intravenous iron supplementation are the main treatment for anaemia in patients with chronic kidney disease. Although observational studies suggest better outcomes for patients who achieve higher haemoglobin (Hb) levels, randomized controlled trials comparing higher and lower Hb targets have led to safety concerns over higher targets and to changes in treatment guidelines. Quarterly data from 2005 to 2013 were obtained on 28 936 haemodialysis patients from the UK Renal Registry. We examined trends in ESA use and average dose, Hb and ferritin values over time and Hb according to the UK Renal Association guideline range. The average ESA dose declined over time, with sharper decreases of epoetin seen towards the end of 2006 and from 2009. Average Hb for patients on ESAs was 114.1 g/L [95% confidence interval (CI) 113.7, 114.6] in the first quarter of 2005, which decreased to 109.6 g/L (95% CI 109.3, 109.9) by the end of 2013. Average serum ferritin was 353 µg/L (95% CI 345, 360) at the start of 2005, increasing to 386 µg/L (95% CI 380, 392) in the final quarter of 2013. The percentage of patients with Hb in the range of 100-120 g/L increased from 46.1 at the start of 2005 to 57.6 at the end of 2013. Anaemia management patterns for haemodialysis patients changed in the UK between 2005 and 2013. These patterns most likely reflect clinician response to emerging trial evidence and practice guidelines. Registries play an important role in continued observation of anaemia management and will monitor further changes as new evidence on optimal care emerges. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

A distance-controlled nanoparticle array using PEGylated ferritin

NASA Astrophysics Data System (ADS)

He, Chao; Uenuma, Mutsunori; Okamoto, Naofumi; Kamitake, Hiroki; Ishikawa, Yasuaki; Yamashita, Ichiro; Uraoka, Yukiharu

2014-12-01

A distance-controlled nanoparticle (NP) array was investigated using a simple spin coating process. It was found that the separation distance of NPs was controlled at the nanoscale by using polyethylene glycols (PEGs). Ferritin was used to synthesize NPs and carry them to a substrate by using the different molecular weight of PEGs. In order to control the distance of the NPs, PEGs with molecular weights of 2k, 5k, 10k and 20k were modified on ferritin with 10 mM ion strength and 0.01 mg ml-1 ferritin concentration. The separated distances of NPs increased along with increase in PEG molecular weight.

Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, A.G.; Carthew, P.; Francis, J.E.

1990-12-01

After a single subcutaneous dose of iron-dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67-, 42- and 21-fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron-positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of themore » study, the size of the inclusions (which were not membrane-limited) increased to greater than 3 microns in diameter, occupying greater than 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x-ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope. These findings are consistent with the hypothesis that in iron-loaded mouse hepatocytes there is a slow passage of ferritin-molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes.« less

Ferritin: the protein nanocage and iron biomineral in health and in disease.

PubMed

Theil, Elizabeth C

2013-11-04

At the center of iron and oxidant metabolism is the ferritin superfamily: protein cages with Fe(2+) ion channels and two catalytic Fe/O redox centers that initiate the formation of caged Fe2O3·H2O. Ferritin nanominerals, initiated within the protein cage, grow inside the cage cavity (5 or 8 nm in diameter). Ferritins contribute to normal iron flow, maintenance of iron concentrates for iron cofactor syntheses, sequestration of iron from invading pathogens, oxidant protection, oxidative stress recovery, and, in diseases where iron accumulates excessively, iron chelation strategies. In eukaryotic ferritins, biomineral order/crystallinity is influenced by nucleation channels between active sites and the mineral growth cavity. Animal ferritin cages contain, uniquely, mixtures of catalytically active (H) and inactive (L) polypeptide subunits with varied rates of Fe(2+)/O2 catalysis and mineral crystallinity. The relatively low mineral order in liver ferritin, for example, coincides with a high percentage of L subunits and, thus, a low percentage of catalytic sites and nucleation channels. Low mineral order facilitates rapid iron turnover and the physiological role of liver ferritin as a general iron source for other tissues. Here, current concepts of ferritin structure/function/genetic regulation are discussed and related to possible therapeutic targets such as mini-ferritin/Dps protein active sites (selective pathogen inhibition in infection), nanocage pores (iron chelation in therapeutic hypertransfusion), mRNA noncoding, IRE riboregulator (normalizing the ferritin iron content after therapeutic hypertransfusion), and protein nanovessels to deliver medicinal or sensor cargo.

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton

PubMed Central

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-01-01

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID:26553998

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton.

PubMed

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-11-24

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation.

Ferritin gene organization: differences between plants and animals suggest possible kingdom-specific selective constraints.

PubMed

Proudhon, D; Wei, J; Briat, J; Theil, E C

1996-03-01

Ferritin, a protein widespread in nature, concentrates iron approximately 10(11)-10(12)-fold above the solubility within a spherical shell of 24 subunits; it derives in plants and animals from a common ancestor (based on sequence) but displays a cytoplasmic location in animals compared to the plastid in contemporary plants. Ferritin gene regulation in plants and animals is altered by development, hormones, and excess iron; iron signals target DNA in plants but mRNA in animals. Evolution has thus conserved the two end points of ferritin gene expression, the physiological signals and the protein structure, while allowing some divergence of the genetic mechanisms. Comparison of ferritin gene organization in plants and animals, made possible by the cloning of a dicot (soybean) ferritin gene presented here and the recent cloning of two monocot (maize) ferritin genes, shows evolutionary divergence in ferritin gene organization between plants and animals but conservation among plants or among animals; divergence in the genetic mechanism for iron regulation is reflected by the absence in all three plant genes of the IRE, a highly conserved, noncoding sequence in vertebrate animal ferritin mRNA. In plant ferritin genes, the number of introns (n = 7) is higher than in animals (n = 3). Second, no intron positions are conserved when ferritin genes of plants and animals are compared, although all ferritin gene introns are in the coding region; within kingdoms, the intron positions in ferritin genes are conserved. Finally, secondary protein structure has no apparent relationship to intron/exon boundaries in plant ferritin genes, whereas in animal ferritin genes the correspondence is high. The structural differences in introns/exons among phylogenetically related ferritin coding sequences and the high conservation of the gene structure within plant or animal kingdoms of the gene structure within plant or animal kingdoms suggest that kingdom-specific functional constraints may

On the mineral core of ferritin-like proteins: structural and magnetic characterization

NASA Astrophysics Data System (ADS)

García-Prieto, A.; Alonso, J.; Muñoz, D.; Marcano, L.; Abad Díaz de Cerio, A.; Fernández de Luis, R.; Orue, I.; Mathon, O.; Muela, A.; Fdez-Gubieda, M. L.

2015-12-01

It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K-edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction.It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM

Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome

PubMed Central

Petroni, Roberta Cardoso; da Rosa, Susana Elaine Alves; de Carvalho, Flavia Pereira; Santana, Rúbia Anita Ferraz; Hyppolito, Joyce Esteves; Nascimento, Claudia Mac Donald Bley; Hamerschlak, Nelson; Campregher, Paulo Vidal

2017-01-01

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5’UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5’UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice. PMID:28746593

Ferritin-Triggered Redox Cycling for Highly Sensitive Electrochemical Immunosensing of Protein.

PubMed

Akanda, Md Rajibul; Ju, Huangxian

2018-06-04

Electrochemical immunoassay amplified with redox cycling has become a challenging topic in highly sensitive analysis of biomarkers. Here a ferritin-triggered redox cycling is reported by using a highly outersphere reaction-philic (OSR-philic) redox mediator ruthenium hexamine (Ru(NH3)63+) to perform the OSR-philic/innersphere reaction-philic (ISR-philic) controlled signal amplification. The screened mediator can meet the needs of lower E0 than ferritin, low reactivity with ISR-philic species, and quick electron exchange with ferritin redox couple. The ferritin-labeled antibody is firstly bounded to immunosensor surface by recognizing the target antigen capured by the immobilized primary antibody. The ferritin then mediates OSR-philic/ISR-philic transfer from Ru(NH3)63+/2+/immunosensor to ferritin-H2O2 redox system. The fast mediation and excellent resistant of highly OSR-philic Ru(NH3)63+ against radical oxygen species lead to highly sensitive electrochemical readout and high signal-to-background ratio. The proposed redox cycling greatly enhances the readout signal and the sensitivity of traditional ferritin-labelled sandwich immunoassay. Using Enteropathogenic Coli (E. Coli) antigen as a model analyte, the developed method shows excellent linearity over the concentration range from 10.0 pg/mL to 0.1 µg/mL and a detection limit of 10.0 fg/mL. The acceptable accuracy, good reproducibility and selectivity of the proposed immunoassay method in real samples indicate the superior practicability of the ferritin-triggered redox cycling.

The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry

PubMed Central

Maruyama, Yukio; Yokoyama, Keitaro; Yokoo, Takashi; Shigematsu, Takashi; Iseki, Kunitoshi; Tsubakihara, Yoshiharu

2015-01-01

Background/Aims Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD). Methods Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008. Results Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31–1.81 and HR, 1.44; 95% CI, 1.13–1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79–1.65). Conclusions Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients. PMID:26599216

Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2013-12-01

targeted liposomes containing H- ferritin caused a 9.5 day extension of lifespan as compared to No Surgery; this effect is trending strongly towards... Ferritin 2.0 mg/ml groups, respectively. There is a trend towards significance in overall survival, p =0.09. 20 Figure 3 Figure 3...in the No Surgery, aCSF, and H- Ferritin groups, respectively. There is a trend towards significance, p =0.11. 24 Figure 7 Figure 7

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels*

PubMed Central

Chandramouli, Balasubramanian; Bernacchioni, Caterina; Di Maio, Danilo; Turano, Paola; Brancato, Giuseppe

2016-01-01

Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe2+-loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe2+ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe2+ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H′ protein and some of its variants as case studies. We describe the structural features that determine Fe2+ translocation with atomistic detail, and we propose a putative mechanism for Fe2+ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin. PMID:27756844

Iron stores and obesity are negatively associated with ovarian volume and anti-Müllerian hormone levels in women with polycystic ovary syndrome.

PubMed

Yang, Jehn-Hsiahn; Chou, Chia-Hung; Yang, Wei-Shiung; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

2015-12-01

Obesity and insulin resistance are associated with increased iron stores, but have conflicting effects on ovarian reserve in women with polycystic ovary syndrome (PCOS). Iron-catalyzed oxidative stress might be detrimental to ovarian tissue and granulosa cell function. In this study we determined the association between body iron stores, obesity, and ovarian reserve in women with PCOS. One hundred and fifty-six women diagnosed with PCOS according to Rotterdam criteria and 30 normoweight healthy control women were enrolled in this cross-sectional study. Ovarian volume, total antral follicle count, and the anti-Müllerian hormone (AMH) level were measured as an indicator of ovarian reserve. Ferritin and transferrin-bound iron levels were significantly higher in women with PCOS than normoweight controls. Obese women with PCOS had higher ferritin levels (p = 0.006), but lower AMH levels (p < 0.0001) than nonobese women with PCOS. Using univariate analysis, the AMH level and mean ovarian volume were inversely related to the ferritin level, homeostasis model assessment of insulin resistance, and body mass index in women with PCOS. Body mass index and ferritin level remained significantly correlated with a lower AMH level and reduced ovarian volume, respectively, after considering other confounding variables. An elevated ferritin level and obesity were negatively associated with ovarian volume and the AMH level, respectively, in women with PCOS. Copyright © 2015. Published by Elsevier B.V.

Ferritin accumulation and degradation in different organs of pea (Pisum sativum) during development.

PubMed Central

Lobreaux, S; Briat, J F

1991-01-01

Iron concentration and ferritin distribution have been determined in different organs of pea (Pisum sativum) during development under conditions of continuous iron supply from hydroponic cultures. No ferritin was detected in total protein extracts from roots or leaves. However, a transient iron accumulation in the roots, which corresponds to an increase in iron uptake, was observed when young fruits started to develop. Ferritin was detectable in total protein extracts of flowers and pods, and it accumulated in seeds. In seeds, the same relative amount of ferritin was detected in cotyledons and in the embryo axis. In cotyledons, ferritin and iron concentration decrease progressively during the first week of germination. Ferritin in the embryo axis was processed, and disappeared, during germination, within the first 4 days of radicle and epicotyl growth. This degradation of ferritin in vivo was marked by a shortening of a 28 kDa subunit, giving 26.5 and 25 kDa polypeptides, reminiscent of the radical damage occurring in pea seed ferritin during iron exchange in vitro [Laulhere, Laboure & Briat (1989) J. Biol. Chem. 264, 3629-3635]. Developmental control of iron concentration and ferritin distribution in different organs of pea is discussed. Images Fig. 4. Fig. 6. Fig. 7. PMID:2006922

Endosperm-specific co-expression of recombinant soybean ferritin and Aspergillus phytase in maize results in significant increases in the levels of bioavailable iron.

PubMed

Drakakaki, Georgia; Marcel, Sylvain; Glahn, Raymond P; Lund, Elizabeth K; Pariagh, Sandra; Fischer, Rainer; Christou, Paul; Stoger, Eva

2005-12-01

We have generated transgenic maize plants expressing Aspergillus phytase either alone or in combination with the iron-binding protein ferritin. Our aim was to produce grains with increased amounts of bioavailable iron in the endosperm. Maize seeds expressing recombinant phytase showed enzymatic activities of up to 3 IU per gram of seed. In flour paste prepared from these seeds, up to 95% of the endogenous phytic acid was degraded, with a concomitant increase in the amount of available phosphate. In seeds expressing ferritin in addition to phytase, the total iron content was significantly increased. To evaluate the impact of the recombinant proteins on iron absorption in the human gut, we used an in vitro digestion/Caco-2 cell model. We found that phytase in the maize seeds was associated with increased cellular iron uptake, and that the rate of iron uptake correlated with the level of phytase expression regardless of the total iron content of the seeds. We also investigated iron bioavailability under more complex meal conditions by adding ascorbic acid, which promotes iron uptake, to all samples. This resulted in a further increase in iron absorption, but the effects of phytase and ascorbic acid were not additive. We conclude that the expression of recombinant ferritin and phytase could help to increase iron availability and enhance the absorption of iron, particularly in cereal-based diets that lack other nutritional components.

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners

PubMed Central

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-01-01

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT (p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW (p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW (p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron. PMID:28335426

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners.

PubMed

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-03-14

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT ( p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW ( p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW ( p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron.

Distinct Mechanisms of Ferritin Delivery to Lysosomes in Iron-Depleted and Iron-Replete Cells ▿

PubMed Central

Asano, Takeshi; Komatsu, Masaaki; Yamaguchi-Iwai, Yuko; Ishikawa, Fuyuki; Mizushima, Noboru; Iwai, Kazuhiro

2011-01-01

Ferritin is a cytosolic protein that stores excess iron, thereby protecting cells from iron toxicity. Ferritin-stored iron is believed to be utilized when cells become iron deficient; however, the mechanisms underlying the extraction of iron from ferritin have yet to be fully elucidated. Here, we demonstrate that ferritin is degraded in the lysosome under iron-depleted conditions and that the acidic environment of the lysosome is crucial for iron extraction from ferritin and utilization by cells. Ferritin was targeted for degradation in the lysosome even under iron-replete conditions in primary cells; however, the mechanisms underlying lysosomal targeting of ferritin were distinct under depleted and replete conditions. In iron-depleted cells, ferritin was targeted to the lysosome via a mechanism that involved autophagy. In contrast, lysosomal targeting of ferritin in iron-replete cells did not involve autophagy. The autophagy-independent pathway of ferritin delivery to lysosomes was deficient in several cancer-derived cells, and cancer-derived cell lines are more resistant to iron toxicity than primary cells. Collectively, these results suggest that ferritin trafficking may be differentially regulated by cell type and that loss of ferritin delivery to the lysosome under iron-replete conditions may be related to oncogenic cellular transformation. PMID:21444722

Amino-acid sequence and predicted three-dimensional structure of pea seed (Pisum sativum) ferritin.

PubMed Central

Lobreaux, S; Yewdall, S J; Briat, J F; Harrison, P M

1992-01-01

The iron storage protein, ferritin, is widely distributed in the living kingdom. Here the complete cDNA and derived amino-acid sequence of pea seed ferritin are described, together with its predicted secondary structure, namely a four-helix-bundle fold similar to those of mammalian ferritins, with a fifth short helix at the C-terminus. An N-terminal extension of 71 residues contains a transit peptide (first 47 residues) responsible for plastid targetting as in other plant ferritins, and this is cleaved before assembly. The second part of the extension (24 residues) belongs to the mature subunit; it is cleaved during germination. The amino-acid sequence of pea seed ferritin is aligned with those of other ferritins (49% amino-acid identity with H-chains and 40% with L-chains of human liver ferritin in the aligned region). A three-dimensional model has been constructed by fitting the aligned sequence to the coordinates of human H-chains, with appropriate modifications. A folded conformation with an 11-residue helix is predicted for the N-terminal extension. As in mammalian ferritins, 24 subunits assemble into a hollow shell. In pea seed ferritin, its N-terminal extension is exposed on the outside surface of the shell. Within each pea subunit is a ferroxidase centre resembling those of human ferritin H-chains except for a replacement of Glu-62 by His. The channel at the 4-fold-symmetry axes defined by E-helices, is predicted to be hydrophilic in plant ferritins, whereas it is hydrophobic in mammalian ferritins. Images Fig. 3. Fig. 5. Fig. 6. PMID:1472006

Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development.

PubMed

González-Morales, Nicanor; Mendoza-Ortíz, Miguel Ángel; Blowes, Liisa M; Missirlis, Fanis; Riesgo-Escovar, Juan R

2015-01-01

In Drosophila melanogaster, iron is stored in the cellular endomembrane system inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. In larvae, ferritin accumulates in the midgut, hemolymph, garland, pericardial cells and in the nervous system. Here we present analyses of embryonic phenotypes for mutations in Fer1HCH, Fer2LCH and in both genes simultaneously. Mutations in either gene or deletion of both genes results in a similar set of cuticular embryonic phenotypes, ranging from non-deposition of cuticle to defects associated with germ band retraction, dorsal closure and head involution. A fraction of ferritin mutants have embryonic nervous systems with ventral nerve cord disruptions, misguided axonal projections and brain malformations. Ferritin mutants die with ectopic apoptotic events. Furthermore, we show that ferritin maternal contribution, which varies reflecting the mother's iron stores, is used in early development. We also evaluated phenotypes arising from the blockage of COPII transport from the endoplasmic reticulum to the Golgi apparatus, feeding the secretory pathway, plus analysis of ectopically expressed and fluorescently marked Fer1HCH and Fer2LCH. Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. These functions are required in multiple tissues during Drosophila embryonic development.

Behavioral decline and premature lethality upon pan-neuronal ferritin overexpression in Drosophila infected with a virulent form of Wolbachia

PubMed Central

Kosmidis, Stylianos; Missirlis, Fanis; Botella, Jose A.; Schneuwly, Stephan; Rouault, Tracey A.; Skoulakis, Efthimios M. C.

2014-01-01

Iron is required for organismal growth. Therefore, limiting iron availability may be a key part of the host’s innate immune response to various pathogens, for example, in Drosophila infected with Zygomycetes. One way the host can transiently reduce iron bioavailability is by ferritin overexpression. To study the effects of neuronal-specific ferritin overexpression on survival and neurodegeneration we generated flies simultaneously over-expressing transgenes for both ferritin subunits in all neurons. We used two independent recombinant chromosomes bearing UAS-Fer1HCH, UAS-Fer2LCH transgenes and obtained qualitatively different levels of late-onset behavioral and lifespan declines. We subsequently discovered that one parental strain had been infected with a virulent form of the bacterial endosymbiont Wolbachia, causing widespread neuronal apoptosis and premature death. This phenotype was exacerbated by ferritin overexpression and was curable by antibiotic treatment. Neuronal ferritin overexpression in uninfected flies did not cause evident neurodegeneration but resulted in a late-onset behavioral decline, as previously reported for ferritin overexpression in glia. The results suggest that ferritin overexpression in the central nervous system of flies is tolerated well in young individuals with adverse manifestations appearing only late in life or under unrelated pathophysiological conditions. PMID:24772084

Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-03-01

tech- jects prior to their participation included standard radio- ques , using- radioisotopes ("SFe and S"Tcm-- diphospho- graphic surveys for evidence of... es were apparent by the third dive day for iron and the iv than ABN. It is of interest that no VGE were heard ajt seventh dive day for ferrtin. No...source of the increased amounts of ferritin levels in acute bepatocellular damage from serum ferritin and iron found during these dives ap.- paracetamol

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels.

PubMed

Chandramouli, Balasubramanian; Bernacchioni, Caterina; Di Maio, Danilo; Turano, Paola; Brancato, Giuseppe

2016-12-02

Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe 2+ -loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe 2+ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe 2+ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H' protein and some of its variants as case studies. We describe the structural features that determine Fe 2+ translocation with atomistic detail, and we propose a putative mechanism for Fe 2+ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Purification and cDNA cloning of ferritin from the hepatopancreas of the freshwater crayfish Pacifastacus leniusculus.

PubMed

Huang, T S; Law, J H; Söderhäll, K

1996-03-01

Ferritin was purified from the hepatopancreas of the freshwater crayfish Pacifastacus leniusculus after injection of iron. It has the same size as horse spleen ferritin (440 kDa) and migrates as two bands, 19 kDa and 20 kDa, respectively, in SDS/PAGE under reducing conditions. Crayfish ferritin (20 kDa) was cloned from a hepatopancreas cDNA library. The deduced amino acid sequence of the crayfish ferritin shows a closer relationship to vertebrate ferritin heavy chains than to insect ferritin and contains the conserved H-specific residues for the ferroxidase centre found in vertebrate ferritin heavy chain. An IRE(iron-responsive element)-like sequence with a predicted stem-loop structure was present in the 5' untranslated region of the crayfish ferritin mRNA. Crayfish ferritin does not share the atypical properties of insect ferritins, such as high molecular mass of intact protein, abundance in hemolymph, and export into vacuoles. We suggest that there are two different types of ferritins distributed in different species: insect-type or secretory ferritins which are predominant in the snail oocyte and insects, and vertebrate (crustacean)-type or cytosolic ferritins which are predominant in vertebrates and crustacea.

Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2013-09-01

and 129 days in the No Surgery, aCSF, and H- Ferritin 2.0 mg/ml groups, respectively. There is a trend towards significance in overall survival, p...H- Ferritin 4.0 mg/ml groups, respectively. There is a trend towards a significant extension of lifespan with aCSF, p =0.09. 21 Figure 5...125.75 days, 131 days, and 128 days in the No Surgery, aCSF, and H- Ferritin groups, respectively. There is a trend towards significance, p =0.11

Biologically Derived Nanoparticle Arrays via a Site-Specific Reconstitution of Ferritin and their Electrochemistry

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; King, Glen C.; Elliott, James R.; Chu, Sang-Hyon; Park, Yeonjoon; Watt, Gerald D.

2004-01-01

Nanoparticle arrays biologically derived from an electrochemically-controlled site-specific biomineralization were fabricated on a gold substrate through the immobilization process of biomolecules. The work reported herein includes the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritins with different inorganic cores, the fabrication of self-assembled arrays with the immobilized ferritin, and the electrochemical characterization of various core materials. Protein immobilization on the substrate is achieved by anchoring ferritins with dithiobis-N-succinimidyl propionate (DTSP). A reconstitution process of electrochemical site-specific biomineralization with a protein cage loads ferritins with different core materials such as Pt, Co, Mn, and Ni. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. The nano-sized metalcored ferritins on a gold substrate displayed a good electrochemical activity for the electron transport and storage, which is suitable for bioelectronics applications such as biofuel cell, bionanobattery, biosensors, etc. Keywords: Ferritin, immobilization, site-specific reconstitution, biomineralization, and bioelectronics

Characteristics of trapping various organophosphorus pesticides with a ferritin reactor of shark liver (Sphyrna zygaena).

PubMed

Huang, He-Qing; Xiao, Zhi-Qun; Lin, Qing-Mei; Chen, Ping

2005-03-15

A reactor is composed of liver ferritin of Sphyrna zygaena (SZLF) and an oscillating bag. A reactive procedure for trapping various organphosphorus pesticides (OPs) with the SZLF reactor in the flowing water is described in detail, showing the maximal trapping numbers of 28 +/-1.0 dichlorovos/SZLF, 42 +/- 1.0 dimethoate/SZLF, and 55 +/- 1.0 methamido-phos/SZLF determined by a improved spectrophotometric method in 12 h. In addition, it is found that the OP numbers trapped by the reactor increase along with the incubation time and its concentration increment in the flowing water (or seawater), respectively. This trapping capacity is considered to depend on the composition of amino acids on the surface of the ferritin shell interior rather than the available volume within the shell. A novel pathway for trapping various OPs with the ferritin is suggested in reference to unstable characteristics of the protein subunits. We claim that the ferritin reactor will be employed to monitor the contamination level of various OPs in the flowing water continuously.

Human-brain ferritin studied by muon spin rotation: a pilot study

NASA Astrophysics Data System (ADS)

Bossoni, Lucia; Grand Moursel, Laure; Bulk, Marjolein; Simon, Brecht G.; Webb, Andrew; van der Weerd, Louise; Huber, Martina; Carretta, Pietro; Lascialfari, Alessandro; Oosterkamp, Tjerk H.

2017-10-01

Muon spin rotation is employed to investigate the spin dynamics of ferritin proteins isolated from the brain of an Alzheimer’s disease (AD) patient and of a healthy control, using a sample of horse-spleen ferritin as a reference. A model based on the Néel theory of superparamagnetism is developed in order to interpret the spin relaxation rate of the muons stopped by the core of the protein. Using this model, our preliminary observations show that ferritins from the healthy control are filled with a mineral compatible with ferrihydrite, while ferritins from the AD patient contain a crystalline phase with a larger magnetocrystalline anisotropy, possibly compatible with magnetite or maghemite.

Is serum ferritin within the reference range a risk predictor of cardiovascular disease? A population-based, long-term study comprising 2874 subjects.

PubMed

Friedrich, Nele; Milman, Nils; Völzke, Henry; Linneberg, Allan; Jørgensen, Torben

2009-08-01

The 'iron hypothesis' claims that Fe depletion protects against IHD. The objective of the present study was to investigate the associations between serum ferritin levels and the risk of CVD and IHD in a population-based sample. A total of 2874 subjects with serum ferritin levels between 15 and 300 microg/l from the Danish part of the 'Monitoring of Trends and Determinants in Cardiovascular Disease' (DAN-MONICA) I study and the 1914 Cohort survey were followed for 10 years. Information on behavioural and socio-demographic characteristics were collected and serum ferritin levels measured. Non-fatal and fatal CVD and IHD were identified by the International Classification of Diseases diagnoses numbers. Multivariable Cox proportional hazard regression models with restricted cubic splines were performed. During the follow-up period, 310 subjects (201 men; 109 women) and 161 subjects (117 men; forty-four women) experienced CVD and IHD, respectively. Our analyses revealed no statistically significant associations between serum ferritin levels and the risk of CVD or IHD in both sexes. However, in women, the results argue for a U-shaped relationship between serum ferritin levels and CVD as well as IHD. In concordance with former prospective studies, the present results do not support the hypothesis that normal body Fe stores should play a significant role in the development of CVD.

Erythropoiesis-stimulating agent dosing, haemoglobin and ferritin levels in UK haemodialysis patients 2005–13

PubMed Central

Caskey, Fergus; Ben-Shlomo, Yoav; Sterne, Jonathan A.C.; Gilg, Julie; Nitsch, Dorothea; Tomson, Charles

2017-01-01

ABSTRACT Background: Erythropoiesis-stimulating agents (ESAs) with intravenous iron supplementation are the main treatment for anaemia in patients with chronic kidney disease. Although observational studies suggest better outcomes for patients who achieve higher haemoglobin (Hb) levels, randomized controlled trials comparing higher and lower Hb targets have led to safety concerns over higher targets and to changes in treatment guidelines. Methods: Quarterly data from 2005 to 2013 were obtained on 28 936 haemodialysis patients from the UK Renal Registry. We examined trends in ESA use and average dose, Hb and ferritin values over time and Hb according to the UK Renal Association guideline range. Results: The average ESA dose declined over time, with sharper decreases of epoetin seen towards the end of 2006 and from 2009. Average Hb for patients on ESAs was 114.1 g/L [95% confidence interval (CI) 113.7, 114.6] in the first quarter of 2005, which decreased to 109.6 g/L (95% CI 109.3, 109.9) by the end of 2013. Average serum ferritin was 353 µg/L (95% CI 345, 360) at the start of 2005, increasing to 386 µg/L (95% CI 380, 392) in the final quarter of 2013. The percentage of patients with Hb in the range of 100–120 g/L increased from 46.1 at the start of 2005 to 57.6 at the end of 2013. Conclusions: Anaemia management patterns for haemodialysis patients changed in the UK between 2005 and 2013. These patterns most likely reflect clinician response to emerging trial evidence and practice guidelines. Registries play an important role in continued observation of anaemia management and will monitor further changes as new evidence on optimal care emerges. PMID:27190350

Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded by mutation.

PubMed

Hasan, Mohammad R; Tosha, Takehiko; Theil, Elizabeth C

2008-11-14

Ferric minerals in ferritins are protected from cytoplasmic reductants and Fe2+ release by the protein nanocage until iron need is signaled. Deletion of ferritin genes is lethal; two critical ferritin functions are concentrating iron and oxidant protection (consuming cytoplasmic iron and oxygen in the mineral). In solution, opening/closing (gating) of eight ferritin protein pores controls reactions between external reductant and the ferritin mineral; pore gating is altered by mutation, low heat, and physiological urea (1 mm) and monitored by CD spectroscopy, protein crystallography, and Fe2+ release rates. To study the effects of a ferritin pore gating mutation in living cells, we cloned/expressed human ferritin H and H L138P, homologous to the frog open pore model that was unexpressable in human cells. Human ferritin H L138P behaved like the open pore ferritin model in vitro as follows: (i) normal protein cage assembly and mineralization, (ii) increased iron release (t1/2) decreased 17-fold), and (iii) decreased alpha-helix (8%). Overexpression (> 4-fold), in HeLa cells, showed for ferritin H L138P equal protein expression and total cell 59Fe but increased chelatable iron, 16%, p < 0.01 (59Fe in the deferoxamine-containing medium), and decreased 59Fe in ferritin, 28%, p < 0.01, compared with wild type. The coincidence of decreased 59Fe in open pore ferritin with increased chelatable 59Fe in cells expressing the ferritin open pore mutation suggests that ferritin pore gating influences to the amount of iron (59Fe) in ferritin in vivo.

A case of acute infectious mononucleosis presenting with very high ferritin

PubMed Central

Thoufeeq, Muhammed Hameed; Ali Khan, Shahul Leyakath; Jain, Sanjiv Kumar; Al-Shakerchi, Hasanain; Hussain, Munem

2007-01-01

Hepatitis is an important but uncommon manifestation of acute Epstein Barr infection. Infectious mononucleosis is usually a disease of young adults. We report a case of infectious mononucleosis in a 72-year old jaundiced gentleman with ferritin level of 2438 that normalised on clinical improvement. PMID:17278235

Hybrid magnetic materials formed by ferritin intercalated into a layered double hydroxide

NASA Astrophysics Data System (ADS)

Clemente-León, Miguel; Coronado, Eugenio; Primo, Vicent; Ribera, Antonio; Soriano-Portillo, Alejandra

2008-12-01

A hybrid magnetic material formed by ferritin intercalated into a layered double hydroxide (LDH) of Mg and Al (Mg/Al molar ratio 2) is prepared and characterized through powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, electron probe microanalysis (EPMA) and high resolution transmission electron microscopy (HRTEM). One observes an enhancement in the thermal stability of the ferritin molecules when they are inserted in the layered material. Magnetic measurements of the hybrid material exhibit the typical superparamagnetic behaviour of the ferritin molecule. On the other hand, the intercalation of ferritin into the LDH guarantees a homogeneous dispersion of the ferritin molecules, which do not aggregate even after calcination of the sample. This feature allows obtaining well-dispersed magnetic metal oxide nanoparticles upon calcination of the hybrid material.

Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

PubMed

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Feucht, Judith; Queudeville, Manon; Teltschik, Heiko-Manuel; Lang, Peter; Feuchtinger, Tobias; Handgretinger, Rupert; Müller, Ingo

2016-01-01

Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers.

Immunocytochemical analysis of the subcellular distribution of ferritin in Imperata cylindrica (L.) Raeuschel, an iron hyperaccumulator plant.

PubMed

de la Fuente, Vicenta; Rodríguez, Nuria; Amils, Ricardo

2012-05-01

Ferritin is of interest at the structural and functional level not only as storage for iron, a critical element, but also as a means to prevent cell damage produced by oxidative stress. The main objective of this work was to confirm by immunocytochemistry the presence and the subcellular distribution of the ferritin detected by Mösbauer spectroscopy in Imperata cylindrica, a plant which accumulates large amounts of iron. The localization of ferritin was performed in epidermal, parenchymal and vascular tissues of shoots and leaves of I. cylindrica. The highest density of immunolabeling in shoots appeared in the intracellular space of cell tissues, near the cell walls and in the cytoplasm. In leaves, ferritin was detected in the proximity of the dense network of the middle lamella of cell walls, following a similar path to that observed in shoots. Immunolabeling was also localized in chloroplasts. The abundance of immunogold labelling in mitochondria for I. cylindrica was rather low, probably because the study dealt with tissues from old plants. These results further expand the localization of ferritin in cell components other than chloroplasts and mitochondria in plants. Copyright © 2011 Elsevier GmbH. All rights reserved.

Iron Release from Soybean Seed Ferritin Induced by Cinnamic Acid Derivatives.

PubMed

Sha, Xuejiao; Chen, Hai; Zhang, Jingsheng; Zhao, Guanghua

2018-05-04

Plant ferritin represents a novel class of iron supplement, which widely co-exists with phenolic acids in a plant diet. However, there are few reports on the effect of these phenolic acids on function of ferritin. In this study, we demonstrated that cinnamic acid derivatives, as widely occurring phenolic acids, can induce iron release from holo soybean seed ferritin (SSF) in a structure-dependent manner. The ability of the iron release from SSF by five cinnamic acids follows the sequence of Cinnamic acid > Chlorogenic acid > Ferulic acid > p -Coumaric acid > Trans -Cinnamic acid. Fluorescence titration in conjunction with dialysis results showed that all of these five compounds have a similar, weak ability to bind with protein, suggesting that their protein-binding ability is not related to their iron release activity. In contrast, both Fe 2+ -chelating activity and reducibility of these cinnamic acid derivatives are in good agreement with their ability to induce iron release from ferritin. These studies indicate that cinnamic acid and its derivatives could have a negative effect on iron stability of holo soybean seed ferritin in diet, and the Fe 2+ -chelating activity and reducibility of cinnamic acid and its derivatives have strong relations to the iron release of soybean seed ferritin.

Ferritin ion channel disorder inhibits Fe(II)/O2 reactivity at distant sites.

PubMed

Tosha, Takehiko; Behera, Rabindra K; Theil, Elizabeth C

2012-11-05

Ferritins, a complex, mineralized, protein nanocage family essential for life, provide iron concentrates and oxidant protection. Protein-based ion channels and Fe(II)/O(2) catalysis initiate conversion of thousands of Fe atoms to caged, ferritin Fe(2)O(3)·H(2)O minerals. The ion channels consist of six helical segments, contributed by 3 of 12 or 24 polypeptide subunits, around the 3-fold cage axes. The channel structure guides entering Fe(II) ions toward multiple, catalytic, diiron sites buried inside ferritin protein helices, ~20 Å away from channel internal exits. The catalytic product, Fe(III)-O(H)-Fe(III), is a mineral precursor; mineral nucleation begins inside the protein cage with mineral growth in the central protein cavity (5-8 nm diameter). Amino acid substitutions that changed ionic or hydrophobic channel interactions R72D, D122R, and L134P increased ion channel structural disorder (protein crystallographic analyses) and increased Fe(II) exit [chelated Fe(II) after ferric mineral reduction/dissolution]. Since substitutions of some channel carboxylate residues diminished ferritin catalysis with no effect on Fe(II) exit, such as E130A and D127A, we investigated catalysis in ferritins with altered Fe(II) exit, R72D, D122R and L134P. The results indicate that simply changing the ionic properties of the channels, as in the R72D variant, need not change the forward catalytic rate. However, both D122R and L134P, which had dramatic effects on ferritin catalysis, also caused larger effects on channel structure and order, contrasting with R72D. All three amino acid substitutions, however, decreased the stability of the catalytic intermediate, diferric peroxo, even though overall ferritin cage structure is very stable, resisting 80 °C and 6 M urea. The localized structural changes in ferritin subdomains that affect ferritin function over long distances illustrate new properties of the protein cage in natural ferritin function and for applied ferritin uses.

MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

NASA Astrophysics Data System (ADS)

Walsh, Edward G.; Mills, David R.; Lim, Sierin; Sana, Barindra; Brilliant, Kate E.; Park, William K. C.

2013-01-01

A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r 1 and r 2. The r 1 and r 2 values of the uniformly distributed modified ferritin were significantly higher ( r 1 = 1,290 mM-1 s-1 and r 2 = 5,740 mM-1 s-1) than values observed for wild-type ferritin (e.g., horse spleen, r 1 = 0.674 mM-1 s-1, r 2 = 95.54 mM-1 s-1). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T2 contrast with negligible T1 effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

Cerebrospinal fluid ferritin in children with viral and bacterial meningitis.

PubMed

Rezaei, M; Mamishi, S; Mahmoudi, S; Pourakbari, B; Khotaei, G; Daneshjou, K; Hashemi, N

2013-01-01

Despite the fact that the prognosis of bacterial meningitis has been improved by the influence of antibiotics, this disease is still one of the significant causes of morbidity and mortality in children. Rapid differentiation between bacterial and aseptic meningitis, and the need for immediate antibiotic treatment in the former, is crucial in the prognosis of these patients. Ferritin is one of the most sensitive biochemical markers investigated in cerebrospinal fluid (CSF) for the early diagnosis of bacterial meningitis. The present study aims to evaluate the diagnostic capability of CSF ferritin in differentiating bacterial and viral meningitis in the paediatric setting. A cross-sectional study was carried out in the referral Children's Medical Center Hospital, Tehran, during 2008 and 2009. According to the inclusion criteria, CSF samples from 42 patients with suspected meningitis were obtained and divided into two meningitis groups, bacterial (n = 18) and viral (n = 24). Ferritin and other routine determinants (i.e., leucocytes, protein and glucose) were compared between the two groups. Ferritin concentration in the bacterial meningitis group was 106.39 +/- 86.96 ng/dL, which was considerably higher than in the viral meningitis group (10.17 +/- 14.09, P < 0.001). Mean CSF protein concentration and cell count were significantly higher in the bacterial meningitis group and showed a positive correlation with CSF ferritin. In conclusion, this study suggests that CSF ferritin concentration is an accurate test for the early differentiation of bacterial and aseptic meningitis; however, further investigation on a larger cohort of patients is required to confirm this finding.

Genetic manipulation of iron biomineralization enhances MR relaxivity in a ferritin-M6A chimeric complex.

PubMed

Radoul, Marina; Lewin, Limor; Cohen, Batya; Oren, Roni; Popov, Stanislav; Davidov, Geula; Vandsburger, Moriel H; Harmelin, Alon; Bitton, Ronit; Greneche, Jean-Marc; Neeman, Michal; Zarivach, Raz

2016-05-23

Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene - ferritin-M6A - in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies.

CHANGES IN FERRITIN H- AND L-CHAINS IN CANINE LENSES WITH AGE-RELATED NUCLEAR CATARACT

PubMed Central

Goralska, Małgorzata; Nagar, Steven; Colitz, Carmen M.H.; Fleisher, Lloyd N.; McGahan, M. Christine

2014-01-01

PURPOSE To determine potential differences in the characteristics of the iron storage protein, ferritin and its heavy (H) and light (L) subunits in fiber cells from cataractous and normal lenses of older dogs. METHODS Lens fiber cell homogenates were analyzed by SDS-PAGE and ferritin chains were immunodetected with ferritin chain-specific antibodies. Ferritin concentration was measured by ELISA. Immunohistochemistry was used to localize ferritin chains in lens sections. RESULTS The concentration of assembled ferritin was comparable in normal and cataractous lenses of similarly aged dogs. The ferritin L-chain detected in both lens types was modified and was about 11 kDa larger (30 kDa) than standard L-chain (19 kDa) purified from canine liver. The H-chain identified in cataractous fiber cells (29 kDa) differed from 21 kDa standard canine H-chain and from 12 kDa modified H-chain present in fiber cells of normal lenses. Histologic analysis revealed that the H-chain was distributed differently throughout cataractous lenses when compared to normal lenses. There was also a difference in subunit makeup of assembled ferritin between the two lens types. Ferritin from cataractous lenses contained more H-chain and bound 11-fold more iron than ferritin from normal lenses. CONCLUSIONS There are significant differences in the characteristics of ferritin H-chain and its distribution in canine cataractous lenses as compared to normal lenses. The higher content of H-chain in assembled ferritin allows this molecule to sequester more iron. In addition the accumulation of H-chain in deeper fiber layers of the lens may be part of a defense mechanism by which the cataractous lens limits iron-catalyzed oxidative damage. PMID:18708625

Antioxidant capacity of parsley cells (Petroselinum crispum L.) in relation to iron-induced ferritin levels and static magnetic field.

PubMed

Rajabbeigi, Elham; Ghanati, Faezeh; Abdolmaleki, Parviz; Payez, Atefeh

2013-12-01

This study was aimed to evaluate antioxidant response of parsley cells to 21 ppm iron and static magnetic field (SMF; 30 mT). The activity of catalase (CAT) and ascorbate peroxidase (APX) and the contents of malonyldialdehyde, iron and ferritin were measured at 6 and 12 h after treatments. Exposure to SMF increased the activity of CAT in treated cells, while combination of iron and SMF treatments as well as iron supply alone decreased CAT activity, compared to that of control cells. Combination of SMF with iron treatment reduced iron content of the cells and ameliorated mal effect of iron on CAT activity. All treatments reduced APX activity; however, the content of total ascorbate increased in response to iron and SMF+iron. The results showed that among the components of antioxidant system of parsley cells, enhanced activity of CAT in SMF-treated cells and increase of ascorbate in SMF+Fe-treated ones were responsible for the maintenance of membranes integrity. Ferritin contents of SMF- and SMF+Fe-treated cells also decreased significantly 12 h after treatments, compared to those of the control cells. These results cast doubt on the proposed functions of ferritin as a putative reactive oxygen species detoxifying molecule.

Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

PubMed

Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

2015-09-01

Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably

Moving Fe2+ from ferritin ion channels to catalytic OH centers depends on conserved protein cage carboxylates.

PubMed

Behera, Rabindra K; Theil, Elizabeth C

2014-06-03

Ferritin biominerals are protein-caged metabolic iron concentrates used for iron-protein cofactors and oxidant protection (Fe(2+) and O2 sequestration). Fe(2+) passage through ion channels in the protein cages, like membrane ion channels, required for ferritin biomineral synthesis, is followed by Fe(2+) substrate movement to ferritin enzyme (Fox) sites. Fe(2+) and O2 substrates are coupled via a diferric peroxo (DFP) intermediate, λmax 650 nm, which decays to [Fe(3+)-O-Fe(3+)] precursors of caged ferritin biominerals. Structural studies show multiple conformations for conserved, carboxylate residues E136 and E57, which are between ferritin ion channel exits and enzymatic sites, suggesting functional connections. Here we show that E136 and E57 are required for ferritin enzyme activity and thus are functional links between ferritin ion channels and enzymatic sites. DFP formation (Kcat and kcat/Km), DFP decay, and protein-caged hydrated ferric oxide accumulation decreased in ferritin E57A and E136A; saturation required higher Fe(2+) concentrations. Divalent cations (both ion channel and intracage binding) selectively inhibit ferritin enzyme activity (block Fe(2+) access), Mn(2+) < Co(2+) < Cu(2+) < Zn(2+), reflecting metal ion-protein binding stabilities. Fe(2+)-Cys126 binding in ferritin ion channels, observed as Cu(2+)-S-Cys126 charge-transfer bands in ferritin E130D UV-vis spectra and resistance to Cu(2+) inhibition in ferritin C126S, was unpredicted. Identifying E57 and E136 links in Fe(2+) movement from ferritin ion channels to ferritin enzyme sites completes a bucket brigade that moves external Fe(2+) into ferritin enzymatic sites. The results clarify Fe(2+) transport within ferritin and model molecular links between membrane ion channels and cytoplasmic destinations.

Moving Fe2+ from ferritin ion channels to catalytic OH centers depends on conserved protein cage carboxylates

PubMed Central

Behera, Rabindra K.; Theil, Elizabeth C.

2014-01-01

Ferritin biominerals are protein-caged metabolic iron concentrates used for iron–protein cofactors and oxidant protection (Fe2+ and O2 sequestration). Fe2+ passage through ion channels in the protein cages, like membrane ion channels, required for ferritin biomineral synthesis, is followed by Fe2+ substrate movement to ferritin enzyme (Fox) sites. Fe2+ and O2 substrates are coupled via a diferric peroxo (DFP) intermediate, λmax 650 nm, which decays to [Fe3+–O–Fe3+] precursors of caged ferritin biominerals. Structural studies show multiple conformations for conserved, carboxylate residues E136 and E57, which are between ferritin ion channel exits and enzymatic sites, suggesting functional connections. Here we show that E136 and E57 are required for ferritin enzyme activity and thus are functional links between ferritin ion channels and enzymatic sites. DFP formation (Kcat and kcat/Km), DFP decay, and protein-caged hydrated ferric oxide accumulation decreased in ferritin E57A and E136A; saturation required higher Fe2+ concentrations. Divalent cations (both ion channel and intracage binding) selectively inhibit ferritin enzyme activity (block Fe2+ access), Mn2+ << Co2+ < Cu2+ < Zn2+, reflecting metal ion–protein binding stabilities. Fe2+–Cys126 binding in ferritin ion channels, observed as Cu2+–S–Cys126 charge-transfer bands in ferritin E130D UV-vis spectra and resistance to Cu2+ inhibition in ferritin C126S, was unpredicted. Identifying E57 and E136 links in Fe2+ movement from ferritin ion channels to ferritin enzyme sites completes a bucket brigade that moves external Fe2+ into ferritin enzymatic sites. The results clarify Fe2+ transport within ferritin and model molecular links between membrane ion channels and cytoplasmic destinations. PMID:24843174

Blood Metal Concentrations of Manganese, Lead, and Cadmium in Relation to Serum Ferritin Levels in Ohio Residents

EPA Science Inventory

The objectives of this study were to assess fcrritin-specific profiles of blood metal concentrations such as manganese, lead, and cadmium and to evaluate whether ferritin may affect the behavior of the blood metals in relation to menstruation, menopause, or sex in Ohio residents....

Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells

NASA Astrophysics Data System (ADS)

Li, Ke; Zhang, Zhi-Ping; Luo, Ming; Yu, Xiang; Han, Yu; Wei, Hong-Ping; Cui, Zong-Qiang; Zhang, Xian-En

2011-12-01

Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging αvβ3 integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging.Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging αvβ3 integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c1nr11132

Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2012-09-01

infusions with or without H- ferritin shows a significant extension of lifespan and a clear trend of increased survival (Figures 7 and 8). Given that the......August 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Apo- Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis 5b. GRANT NUMBER

Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

PubMed

Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

2018-01-01

Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

METAL-DEPENDENT EXPRESSION OF FERRITIN AND LACTOFERRIN BY RESPIRATORY EPITHELIAL CELLS

EPA Science Inventory

Increased availability of catalytically active metal has been associated with an oxidative injury. The sequestration of transition metals within intracellular ferritin confers an antioxidant function to this protein. Such storage by ferritin requires that the metal be transported...

Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption

PubMed Central

Felipe, Avila; Guadalupe, Echeverría; Druso, Pérez; Carlos, Martinez; Pablo, Strobel; Oscar, Castillo; Luis, Villaroel; Diego, Mezzano; Jaime, Rozowski; Inés, Urquiaga; Federico, Leighton

2015-01-01

Background and Aims. Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. Methods and Results. Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose) as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin), hepatic damage markers (GGT, SGOT), and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose) correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. Conclusion. Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men. PMID:26451235

Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption.

PubMed

Avila, Felipe; Echeverría, Guadalupe; Pérez, Druso; Martinez, Carlos; Strobel, Pablo; Castillo, Oscar; Villaroel, Luis; Mezzano, Diego; Rozowski, Jaime; Urquiaga, Inés; Leighton, Federico

2015-01-01

Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose) as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin), hepatic damage markers (GGT, SGOT), and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose) correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men.

Reference values for serum ferritin and percentage of transferrin saturation in Korean children and adolescents.

PubMed

Oh, Hea Lin; Lee, Jun Ah; Kim, Dong Ho; Lim, Jung Sub

2018-03-01

Ferritin reference values vary by age, gender, and ethnicity. We aimed to determine reference values of serum ferritin (SF) and the percentage of transferrin saturation (TSAT) for Korean children and adolescents. We analyzed data from 2,487 participants (1,311 males and 1,176 females) aged 10-20 years from the Korea National Health and Nutrition Examination Survey (2010-2012). We calculated age- and gender-stratified means and percentile values for SF and TSAT. We first plotted mean SF and TSAT by gender and according to age. In males, mean SF tended to be relatively constant among participants aged 10 to 14 years, with an upward trend thereafter. Mean SF trended downward among female participants until the age of 15 years and remained constant thereafter. Thus, significant gender differences in ferritin exist from the age of 14 years. High levels of SF were associated with obesity, and lower SF levels were associated with anemia and menarche status. We established reference values of SF and TSAT according to age and gender. The reference values for SF calculated in this study can be used to test the association between SF values and other defined diseases in Korean children and adolescents.

Genome-wide comparison of ferritin family from Archaea, Bacteria, Eukarya, and Viruses: its distribution, characteristic motif, and phylogenetic relationship

NASA Astrophysics Data System (ADS)

Bai, Lina; Xie, Ting; Hu, Qingqing; Deng, Changyan; Zheng, Rong; Chen, Wanping

2015-10-01

Ferritins are highly conserved proteins that are widely distributed in various species from archaea to humans. The ubiquitous characteristic of these proteins reflects the pivotal contribution of ferritins to the safe storage and timely delivery of iron to achieve iron homeostasis. This study investigated the ferritin genes in 248 genomes from various species, including viruses, archaea, bacteria, and eukarya. The distribution comparison suggests that mammals and eudicots possess abundant ferritin genes, whereas fungi contain very few ferritin genes. Archaea and bacteria show considerable numbers of ferritin genes. Generally, prokaryotes possess three types of ferritin (the typical ferritin, bacterioferritin, and DNA-binding protein from starved cell), whereas eukaryotes have various subunit types of ferritin, thereby indicating the individuation of the ferritin family during evolution. The characteristic motif analysis of ferritins suggested that all key residues specifying the unique structural motifs of ferritin are highly conserved across three domains of life. Meanwhile, the characteristic motifs were also distinguishable between ferritin groups, especially phytoferritins, which show a plant-specific motif. The phylogenetic analyses show that ferritins within the same subfamily or subunits are generally clustered together. The phylogenetic relationships among ferritin members suggest that both gene duplication and horizontal transfer contribute to the wide variety of ferritins, and their possible evolutionary scenario was also proposed. The results contribute to a better understanding of the distribution, characteristic motif, and evolutionary relationship of the ferritin family.

Tracking Temperature-Dependent Relaxation Times of Ferritin Nanomagnets with a Wideband Quantum Spectrometer

NASA Astrophysics Data System (ADS)

Schäfer-Nolte, Eike; Schlipf, Lukas; Ternes, Markus; Reinhard, Friedemann; Kern, Klaus; Wrachtrup, Jörg

2014-11-01

We demonstrate the tracking of the spin dynamics of ensemble and individual magnetic ferritin proteins from cryogenic up to room temperature using the nitrogen-vacancy color center in diamond as a magnetic sensor. We employ different detection protocols to probe the influence of the ferritin nanomagnets on the longitudinal and transverse relaxation of the nitrogen-vacancy center, which enables magnetic sensing over a wide frequency range from Hz to GHz. The temperature dependence of the observed spectral features can be well understood by the thermally induced magnetization reversals of the ferritin and enables the determination of the anisotropy barrier of single ferritin molecules.

Two Kinds of Ferritin Protect Ixodid Ticks from Iron Overload and Consequent Oxidative Stress

PubMed Central

Galay, Remil Linggatong; Umemiya-Shirafuji, Rika; Bacolod, Eugene T.; Maeda, Hiroki; Kusakisako, Kodai; Koyama, Jiro; Tsuji, Naotoshi; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2014-01-01

Ticks are obligate hematophagous parasites that have successfully developed counteractive means against their hosts' immune and hemostatic mechanisms, but their ability to cope with potentially toxic molecules in the blood remains unclear. Iron is important in various physiological processes but can be toxic to living cells when in excess. We previously reported that the hard tick Haemaphysalis longicornis has an intracellular (HlFER1) and a secretory (HlFER2) ferritin, and both are crucial in successful blood feeding and reproduction. Ferritin gene silencing by RNA interference caused reduced feeding capacity, low body weight and high mortality after blood meal, decreased fecundity and morphological abnormalities in the midgut cells. Similar findings were also previously reported after silencing of ferritin genes in another hard tick, Ixodes ricinus. Here we demonstrated the role of ferritin in protecting the hard ticks from oxidative stress. Evaluation of oxidative stress in Hlfer-silenced ticks was performed after blood feeding or injection of ferric ammonium citrate (FAC) through detection of the lipid peroxidation product, malondialdehyde (MDA) and protein oxidation product, protein carbonyl. FAC injection in Hlfer-silenced ticks resulted in high mortality. Higher levels of MDA and protein carbonyl were detected in Hlfer-silenced ticks compared to Luciferase-injected (control) ticks both after blood feeding and FAC injection. Ferric iron accumulation demonstrated by increased staining on native HlFER was observed from 72 h after iron injection in both the whole tick and the midgut. Furthermore, weak iron staining was observed after Hlfer knockdown. Taken together, these results show that tick ferritins are crucial antioxidant molecules that protect the hard tick from iron-mediated oxidative stress during blood feeding. PMID:24594832

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

PubMed Central

Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

2014-01-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin “halos.” Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2–3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6–15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin “halos,” with some processing methods allowing more redistribution of the ferritin tracer than

Mapping bone interstitial fluid movement: displacement of ferritin tracer during histological processing.

PubMed

Ciani, Cesare; Doty, Stephen B; Fritton, Susannah P

2005-09-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based

Investigation of the Iron(II) Release Mechanism of Human H-Ferritin as a Function of pH.

PubMed

Sala, Davide; Ciambellotti, Silvia; Giachetti, Andrea; Turano, Paola; Rosato, Antonio

2017-09-25

We investigated the kinetics of the release of iron(II) ions from the internal cavity of human H-ferritin as a function of pH. Extensive molecular dynamics simulations of the entire 24-mer ferritin provided atomic-level information on the release mechanism. Double protonation of His residues at pH 4 facilitates the removal of the iron ligands within the C3 channel through the formation of salt bridges, resulting in a significantly lower release energy barrier than pH 9.

A longitudinal study of serum ferritin in 319 adolescent Danish boys and girls examined in 1986 and 1992.

PubMed

Milman, N; Byg, K E; Backer, V; Ulrik, C; Graudal, N

1999-10-01

This study examined trends in iron status in adolescents. Serum ferritin was measured in 1986 and 1992 in 319 Danes (161 males) stratified into 5 groups: I. median age 9 yr in 1986 vs. 15 yr in 1992; II. 11 vs. 17 yr; III. 13 vs. 19 yr; IV. 15 vs. 21 yr; V. 17 vs. 23 yr. Males in group I demonstrated no change in ferritin or estimated iron stores in mg/kg; groups II-V displayed an increase in iron status parameters. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in group III, and positively correlated with height velocity in group V. Females in age groups I and II demonstrated a fall in ferritin and estimated iron stores in mg/kg in association with menarche; values were unchanged in groups III and IV, and increased in group V. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in groups I and II. In conclusion, ferritin levels in adolescents display great variation during growth spurt and at menarche. Changes in ferritin showed no consistent association with growth velocity. In both genders, estimated total iron stores increased with age.

Direct evidence of spatially selective iron mineralization using an immobilized ferritin protein cage.

PubMed

Uto, Koichiro; Yamamoto, Kazuya; Kishimoto, Naoko; Muraoka, Masahiro; Aoyagi, Takao; Yamashita, Ichiro

2014-04-01

(Apo)ferritins are cage-shaped proteins which have recently received a great deal of attention because the inner cavity of the protein shell can be used as a size-restricted reaction field for the synthesis of nanomaterials. The biomineralization behavior and inorganic nanoparticle (NP) synthesis mechanism of (apo)ferritin in solution systems have been studied but the mineralization behavior of (apo)ferritin on the substrates has not yet been well studied. Here, we conducted quantitative and kinetic analyses of the mineralization behavior of immobilized (apo)ferritin on a polyelectrolyte multilayer (PEM) using quartz crystal microbalance (QCM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) techniques. We demonstrated that the (apo)ferritin immobilized on a substrate synthesizes a ferrihydrite core within the confines of the protein cage; similar to a solution dispersed system. In addition, we applied a ferritin/apoferritin blended monolayer to the study of iron mineralization and revealed that biomineralization in this system is spatially selective. It is important to understand the mineralization mechanisms for the synthesis of other functional NPs as this approach has potential for a broad range of magnetic, catalytic, and biomedical sensing applications.

Credibility of the measurement of serum ferritin and transferrin receptor as indicators of iron deficiency anemia in hemodialysis patients.

PubMed

Mahdavi, M R; Makhlough, A; Kosaryan, M; Roshan, P

2011-10-01

Anemia is a common complication in uremic patients. Erythropoietin therapy is prescribed in these cases; however, this treatment is not successful in iron deficient patients. Ferritin-based diagnosis of iron deficiency in these patients is a challenging task, as serum ferritin level may be high due to chronic inflammation and mask iron deficiency. In the current study we evaluated the credibility of another indicator of body iron supply, serum transferrin receptor, in hemodialysis patients in two University-based Hospitals in North of Iran. In a cross-sectional study, 53 hemodialysis patients with a mean age of 56 +/- 18.7 years and 30 persons with iron deficiency and normal renal function with a mean age of 20.1 +/- 14.4 years were examined. All hemodialysis patients were on hemodialysis 2-3 times per week for 3-4 hours. All cases were examined for blood hemoglobin content, serum iron, CRP, serum ferritin and serum transferrin receptor levels. The reference ranges introduced by manufacturers were considered as standard ranges for analysis of the results. Using one sample T-test and Fisher's exact test, data were analyzed. p<0.05 was considered as significant. Hemodialysis patients had blood hemoglobin content below normal range (p<0.05 for men, p<0.001 for women) and CRP levels above normal range (p<0.001). In hemodialysis patients, serum ferritin level was significantly higher than control group (p<0.001), whilst serum transferrin receptor levels in the two groups were not significantly different (p=0.69), and both were above defined normal upper limit (p<0.001 for iron deficient patients; p<0.05 for hemodialysis patients). This study showed measurement of serum ferritin in the presence of chronic inflammation induced by renal failure cannot be a credible indicator of body iron supply, while under this certain condition serum transferrin receptor can more appropriately reflect the amount of body iron supply.

Fe(2+) substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization.

PubMed

Behera, Rabindra K; Torres, Rodrigo; Tosha, Takehiko; Bradley, Justin M; Goulding, Celia W; Theil, Elizabeth C

2015-09-01

Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3·H2O), by moving cytoplasmic Fe(2+) through intracage ion channels to cage-embedded enzyme (2Fe(2+)/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe(2+) movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one -CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650 nm (DFP λ max). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe(3+)-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: (1) narrower interior ion channel openings/pores; (2) increased numbers of ion channel protein-metal binding sites, and (3) a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells.

Fe2+ Substrate Transport through Ferritin Protein Cage Ion Channels Influences Enzyme Activity and Biomineralization

PubMed Central

Behera, Rabindra K.; Torres, Rodrigo; Tosha, Takehiko; Bradley, Justin M.; Goulding, Celia W.; Theil, Elizabeth C.

2015-01-01

Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3.H2O), by moving cytoplasmic Fe2+ through intracage ion channels to cage-embedded enzyme (2Fe2+/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe2+ movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one – CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650nm (DFP λmax). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe3+-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: 1. narrower interior ion channel openings/pores, 2. increased numbers of ion channel protein-metal binding sites, and 3. a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells. PMID:26202907

Surface charge dependent separation of modified and hybrid ferritin in native PAGE: Impact of lysine 104.

PubMed

Subhadarshanee, Biswamaitree; Mohanty, Abhinav; Jagdev, Manas Kumar; Vasudevan, Dileep; Behera, Rabindra K

2017-10-01

Preparation of modified and hybrid ferritin provides a great opportunity to understand the mechanisms of iron loading/unloading, protein self-assembly, size constrained nanomaterial synthesis and targeted drug delivery. However, the large size (M.W.=490kDa) has been limiting the separation of different modified and/or hybrid ferritin nanocages from each other in their intact assembled form and further characterization. Native polyacrylamide gel electrophoresis (PAGE) separates proteins on the basis of both charge and mass, while maintaining their overall native structure and activity. Altering surface charge distribution by substitution of amino acid residues located at the external surface of ferritin (K104E & D40A) affected the migration rate in native PAGE while internal modification had little effect. Crystal structures confirmed that ferritin nanocages made up of subunits with single amino acid substitutions retain the overall structure of ferritin nanocage. Taking advantage of K104E migration behavior, formation of hybrid ferritins with subunits of wild type (WT) and K104E were confirmed and separated in native PAGE. Cage integrity and iron loading ability (ferritin activity) were also tested. The migration pattern of hybrid ferritins in native PAGE depends on the subunit ratio (WT: K104E) in the ferritin cage. Our work shows that native PAGE can be exploited in nanobiotechnology, by analyzing modifications of large proteins like ferritin. Native PAGE, a simple, straight-forward technique, can be used to analyze small modification (by altering external surface charge) in large proteins like ferritin, without disintegrating its self-assembled nanocage structure. In doing so, native PAGE can complement the information obtained from mass spectrometry. The confirmation and separation of modified and hybrid ferritin protein nanocages in native PAGE, opens up various prospects of bio-conjugation, which can be useful in targeted drug delivery, nanobiotechnology and

Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells.

PubMed

Li, Ke; Zhang, Zhi-Ping; Luo, Ming; Yu, Xiang; Han, Yu; Wei, Hong-Ping; Cui, Zong-Qiang; Zhang, Xian-En

2012-01-07

Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging α(v)β(3) integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging.

Fe(II) formation after interaction of the amyloid β-peptide with iron-storage protein ferritin.

PubMed

Balejcikova, Lucia; Siposova, Katarina; Kopcansky, Peter; Safarik, Ivo

2018-05-09

The interaction of amyloid β-peptide (Aβ) with the iron-storage protein ferritin was studied in vitro. We have shown that Aβ during fibril formation process is able to reduce Fe(III) from the ferritin core (ferrihydrite) to Fe(II). The Aβ-mediated Fe(III) reduction yielded a two-times-higher concentration of free Fe(II) than the spontaneous formation of Fe(II) by the ferritin itself. We suggest that Aβ can also act as a ferritin-specific metallochaperone-like molecule capturing Fe(III) from the ferritin ferrihydrite core. Our observation may partially explain the formation of Fe(II)-containing minerals in human brains suffering by neurodegenerative diseases.

Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions.

PubMed

Lescure, A M; Massenet, O; Briat, J F

1990-11-15

Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron.

Ferritin light-chain subunits: key elements for the electron transfer across the protein cage.

PubMed

Carmona, Unai; Li, Le; Zhang, Lianbing; Knez, Mato

2014-12-18

The first specific functionality of the light-chain (L-chain) subunit of the universal iron storage protein ferritin was identified. The electrons released during iron-oxidation were transported across the ferritin cage specifically through the L-chains and the inverted electron transport through the L-chains also accelerated the demineralization of ferritin.

Correlation Between C-reactive Protein and Non-enzymatic Antioxidants (Albumin, Ferritin, Uric Acid and Bilirubin) in Hemodialysis Patients.

PubMed

Beciragic, Amela; Resic, Halima; Prohic, Nejra; Karamehic, Jasenko; Smajlovic, Ajdin; Masnic, Fahrudin; Ajanovic, Selma; Coric, Aida

2015-04-01

between serum CRP and uric acid concentration (rho = 0.438, p = 0.001) and statistically significant, positive, linear correlation between serum CRP and total serum bilirubin (rho = 0.510, p = 0.0001) A statistically significant, negative linear correlation was determined between CRP and albumin concentration (rho= -0.393, p = 0.005) as well as statistically significant, negative linear correlation between serum CRP and ferritin control group (rho = -0.391, p = 0.005). Elevated CRP level is a strong and independent predictor of low levels of serum albumin, which indicates that the hypoalbuminemia in hemodialysis patients could be more due to inflammation than malnutrition. There was no statistically significant correlation between CRP and other non enzymatic antioxidants (uric acid, ferritin, bilirubin), which shows that indicators of antioxidant defense in hemodialysis patients must be individually measured to determine their actual stocks and activity.

Solution and solid state NMR approaches to draw iron pathways in the ferritin nanocage.

PubMed

Lalli, Daniela; Turano, Paola

2013-11-19

Ferritins are intracellular proteins that can store thousands of iron(III) ions as a solid mineral. These structures autoassemble from four-helix bundle subunits to form a hollow sphere and are a prototypical example of protein nanocages. The protein acts as a reservoir, encapsulating iron as ferric oxide in its central cavity in a nontoxic and bioavailable form. Scientists have long known the structural details of the protein shell, owing to very high resolution X-ray structures of the apoform. However, the atomic level mechanism governing the multistep biomineralization process remained largely elusive. Through analysis of the chemical behavior of ferritin mutants, chemists have found the role of some residues in key reaction steps. Using Mössbauer and XAS, they have identified some di-iron intermediates of the catalytic reaction trapped by rapid freeze quench. However, structural information about the iron interaction sites remains scarce. The entire process is governed by a number of specific, but weak, interactions between the protein shell and the iron species moving across the cage. While this situation may constitute a major problem for crystallography, NMR spectroscopy represents an optimal tool to detect and characterize transient species involving soluble proteins. Regardless, NMR analysis of the 480 kDa ferritin represents a real challenge. Our interest in ferritin chemistry inspired us to use an original combination of solution and solid state approaches. While the highly symmetric structure of the homo-24-mer frog ferritin greatly simplifies the spectra, the large protein size hinders the efficient coherence transfer in solution, thus preventing the sequence specific assignments. In contrast, extensive (13)C-spin diffusion makes the solution (13)C-(13)C NOESY experiment our gold standard to monitor protein side chains both in the apoprotein alone and in its interaction with paramagnetic iron species, inducing line broadening on the resonances of

First biochemical and crystallographic characterization of a fast-performing ferritin from a marine invertebrate.

PubMed

De Meulenaere, Evelien; Bailey, Jake Brian; Tezcan, Faik Akif; Deheyn, Dimitri Dominique

2017-12-11

Ferritin, a multimeric cage-like enzyme, is integral to iron metabolism across all phyla through the sequestration and storage of iron through efficient ferroxidase activity. While ferritin sequences from ∼900 species have been identified, crystal structures from only 50 species have been reported, the majority from bacterial origin. We recently isolated a secreted ferritin from the marine invertebrate Chaetopterus sp. (parchment tube worm), which resides in muddy coastal seafloors. Here, we present the first ferritin from a marine invertebrate to be crystallized and its biochemical characterization. The initial ferroxidase reaction rate of recombinant Chaetopterus ferritin (ChF) is 8-fold faster than that of recombinant human heavy-chain ferritin (HuHF). To our knowledge, this protein exhibits the fastest catalytic performance ever described for a ferritin variant. In addition to the high-velocity ferroxidase activity, ChF is unique in that it is secreted by Chaetopterus in a bioluminescent mucus. Previous work has linked the availability of Fe 2+ to this long-lived bioluminescence, suggesting a potential function for the secreted ferritin. Comparative biochemical analyses indicated that both ChF and HuHF showed similar behavior toward changes in pH, temperature, and salt concentration. Comparison of their crystal structures shows no significant differences in the catalytic sites. Notable differences were found in the residues that line both 3-fold and 4-fold pores, potentially leading to increased flexibility, reduced steric hindrance, or a more efficient pathway for Fe 2+ transportation to the ferroxidase site. These suggested residues could contribute to the understanding of iron translocation through the ferritin shell to the ferroxidase site. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer.

PubMed

Truffi, Marta; Fiandra, Luisa; Sorrentino, Luca; Monieri, Matteo; Corsi, Fabio; Mazzucchelli, Serena

2016-05-01

Nowadays cancer represents a prominent challenge in clinics. Main achievements in cancer management would be the development of highly accurate and specific diagnostic tools for early detection of cancer onset, and the generation of smart drug delivery systems for targeted chemotherapy release in cancer cells. In this context, protein-based nanocages hold a tremendous potential as devices for theranostics purposes. In particular, ferritin has emerged as an excellent and promising protein-based nanocage thanks to its unique architecture, surface properties and high biocompatibility. By exploiting natural recognition of the Transferrin Receptor 1, which is overexpressed on tumor cells, ferritin nanocages may ensure a proper drug delivery and release. Moreover, researchers have applied surface functionalities on ferritin cages for further providing active tumor targeting. Encapsulation strategies of non metal-containing drugs within ferritin cages have been explored and successfully performed with encouraging results. Various preclinical studies have demonstrated that nanoformulation within ferritin nanocages significantly improved targeted therapy and accurate imaging of cancer cells. Aims of this review are to describe structure and functions of ferritin nanocages, and to provide an overview about the nanotechnological approaches implemented for applying them to cancer diagnosis and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions.

PubMed Central

Lescure, A M; Massenet, O; Briat, J F

1990-01-01

Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron. Images Fig. 2. Fig. 3. PMID:2264818

Systemic and Cerebral Iron Homeostasis in Ferritin Knock-Out Mice

PubMed Central

Li, Wei; Garringer, Holly J.; Goodwin, Charles B.; Richine, Briana; Acton, Anthony; VanDuyn, Natalia; Muhoberac, Barry B.; Irimia-Dominguez, Jose; Chan, Rebecca J.; Peacock, Munro; Nass, Richard; Ghetti, Bernardino; Vidal, Ruben

2015-01-01

Ferritin, a 24-mer heteropolymer of heavy (H) and light (L) subunits, is the main cellular iron storage protein and plays a pivotal role in iron homeostasis by modulating free iron levels thus reducing radical-mediated damage. The H subunit has ferroxidase activity (converting Fe(II) to Fe(III)), while the L subunit promotes iron nucleation and increases ferritin stability. Previous studies on the H gene (Fth) in mice have shown that complete inactivation of Fth is lethal during embryonic development, without ability to compensate by the L subunit. In humans, homozygous loss of the L gene (FTL) is associated with generalized seizure and atypical restless leg syndrome, while mutations in FTL cause a form of neurodegeneration with brain iron accumulation. Here we generated mice with genetic ablation of the Fth and Ftl genes. As previously reported, homozygous loss of the Fth allele on a wild-type Ftl background was embryonic lethal, whereas knock-out of the Ftl allele (Ftl-/-) led to a significant decrease in the percentage of Ftl-/- newborn mice. Analysis of Ftl-/- mice revealed systemic and brain iron dyshomeostasis, without any noticeable signs of neurodegeneration. Our findings indicate that expression of the H subunit can rescue the loss of the L subunit and that H ferritin homopolymers have the capacity to sequester iron in vivo. We also observed that a single allele expressing the H subunit is not sufficient for survival when both alleles encoding the L subunit are absent, suggesting the need of some degree of complementation between the subunits as well as a dosage effect. PMID:25629408

Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain

PubMed Central

Iordanova, B; Goins, WF; Clawson, DS; Hitchens, TK; Ahrens, ET

2017-01-01

The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications. PMID:22996196

Tunability and Stability of Lead Sulfide Quantum Dots in Ferritin

NASA Astrophysics Data System (ADS)

Peterson, J. Ryan; Hansen, Kameron

Quantum dot solar cells have become one of the fastest growing solar cell technologies to date, and lead sulfide has proven to be an efficient absorber. However, one of the primary concerns in dye-sensitized quantum dot solar cell development is core degradation. We have synthesized lead sulfide quantum dots inside of the spherical protein ferritin in order to protect them from photocorrosion. We have studied the band gaps of these quantum dots and found them to be widely tunable inside ferritin just as they are outside the protein shell. In addition, we have examined their stability by measuring changes in photoluminescence as they are exposed to light over minutes and hours and found that the ferritin-enclosed PbS quantum dots have significantly better resistance to photocorrosion. Brigham Young University, National Science Foundation.

Absorption of Iron from Ferritin Is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments123

PubMed Central

Chen, Huijun; Miranda, Constanza; Janser, Heinz; Elsenhans, Bernd; Núñez, Marco T.; Pizarro, Fernando; Schümann, Klaus

2012-01-01

Ferritin iron from food is readily bioavailable to humans and has the potential for treating iron deficiency. Whether ferritin iron absorption is mechanistically different from iron absorption from small iron complexes/salts remains controversial. Here, we studied iron absorption (RBC 59Fe) from radiolabeled ferritin iron (0.5 mg) in healthy women with or without non-ferritin iron competitors, ferrous sulfate, or hemoglobin. A 9-fold excess of non-ferritin iron competitor had no significant effect on ferritin iron absorption. Larger amounts of iron (50 mg and a 99-fold excess of either competitor) inhibited iron absorption. To measure transport rates of iron that was absorbed inside ferritin, rat intestinal segments ex vivo were perfused with radiolabeled ferritin and compared to perfusion with ferric nitrilotriacetic (Fe-NTA), a well-studied form of chelated iron. Intestinal transport of iron absorbed inside exogenous ferritin was 14.8% of the rate measured for iron absorbed from chelated iron. In the steady state, endogenous enterocyte ferritin contained >90% of the iron absorbed from Fe-NTA or ferritin. We found that ferritin is a slow release source of iron, readily available to humans or animals, based on RBC iron incorporation. Ferritin iron is absorbed by a different mechanism than iron salts/chelates or heme iron. Recognition of a second, nonheme iron absorption process, ferritin endocytosis, emphasizes the need for more mechanistic studies on ferritin iron absorption and highlights the potential of ferritin present in foods such as legumes to contribute to solutions for global iron deficiency. PMID:22259191

Upfront dilution of ferritin samples to reduce hook effect, improve turnaround time and reduce costs.

PubMed

Wu, Shu Juan; Hayden, Joshua A

2018-02-15

Sandwich immunoassays offer advantages in the clinical laboratory but can yield erroneously low results due to hook (prozone) effect, especially with analytes whose concentrations span several orders of magnitude such as ferritin. This study investigated a new approach to reduce the likelihood of hook effect in ferritin immunoassays by performing upfront, five-fold dilutions of all samples for ferritin analysis. The impact of this change on turnaround time and costs were also investigated. Ferritin concentrations were analysed in routine clinical practice with and without upfront dilutions on Siemens Centaur® XP (Siemens Healthineers, Erlang, Germany) immunoanalysers. In addition, one month of baseline data (1026 results) were collected prior to implementing upfront dilutions and one month of data (1033 results) were collected after implementation. Without upfront dilutions, hook effect was observed in samples with ferritin concentrations as low as 86,028 µg/L. With upfront dilutions, samples with ferritin concentrations as high as 126,050 µg/L yielded values greater than the measurement interval and would have been diluted until an accurate value was obtained. The implementation of upfront dilution of ferritin samples led to a decrease in turnaround time from a median of 2 hours and 3 minutes to 1 hour and 18 minutes (P = 0.002). Implementation of upfront dilutions of all ferritin samples reduced the possibility of hook effect, improved turnaround time and saved the cost of performing additional dilutions.

Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients.

PubMed

Thomas, C; Kobold, U; Balan, S; Roeddiger, R; Thomas, L

2011-04-01

Biochemical markers of iron deficiency do not distinguish iron-deficient anemia (IDA) from the anemia of chronic disease (ACD) and the combined state of ACD/IDA. Serum hepcidin-25 might be a marker resolving this problem. We investigated the extent to which serum hepcidin-25 enables the differentiation of the states above in comparison with the ferritin index plot, the so-called Thomas plot [soluble transferrin receptor (sTfR)/log ferritin and the reticulocyte hemoglobin content (CHr)]. Serum hepcidin-25 was determined in 155 anemic patients who were classified as having latent iron deficiency (latent ID), IDA, ACD, or ACD/IDA using the ferritin index plot (Thomas plot). Hepcidin-25 was determined using an isotope-dilution micro-HPLC-tandem mass spectrometry method. The ability to discriminate among these states based on serum hepcidin-25 alone or in combination with the CHr was evaluated in a receiver operating characteristic curve analysis and a comparison with the recently established ferritin index plot. Serum hepcidin-25 correlated with ferritin and the ferritin index. Use of a hepcidin-25 cutoff level of ≤4 nmol/l allowed the differentiation of IDA from ACD and ACD/IDA. Furthermore, the discrimination of ACD/IDA from ACD required combination with CHr in a new plot (hepcidin-25 and the CHr). The hepcidin-25 plot and the ferritin index plot showed a good correspondence in the differentiation of iron states in patients with anemia. Patients with IDA can be differentiated from ACD and ACD/IDA but not ACD from ACD/IDA based on hepcidin-25 alone. The combination of hepcidin-25 with CHr in the hepcidin-25 plot was useful for the differentiation of the states above. © 2010 Blackwell Publishing Ltd.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

USGS Publications Warehouse

Langley, J.A.; McKee, K.L.; Cahoon, D.R.; Cherry, J.A.; Megonigala, J.P.

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise.

PubMed

Langley, J Adam; McKee, Karen L; Cahoon, Donald R; Cherry, Julia A; Megonigal, J Patrick

2009-04-14

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO(2) concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO(2)] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO(2) (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr(-1) in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO(2) effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO(2), may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

PubMed Central

Langley, J. Adam; McKee, Karen L.; Cahoon, Donald R.; Cherry, Julia A.; Megonigal, J. Patrick

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1 in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas. PMID:19325121

The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement.

PubMed

Honarmand Ebrahimi, Kourosh; Bill, Eckhard; Hagedoorn, Peter-Leon; Hagen, Wilfred R

2012-11-01

A conserved iron-binding site, the ferroxidase center, regulates the vital iron storage role of the ubiquitous protein ferritin in iron metabolism. It is commonly thought that two Fe(II) simultaneously bind the ferroxidase center and that the oxidized Fe(III)-O(H)-Fe(III) product spontaneously enters the cavity of ferritin as a unit. In contrast, in some bacterioferritins and in archaeal ferritins a persistent di-iron prosthetic group in this center is believed to mediate catalysis of core formation. Using a combination of binding experiments and isotopically labeled (57)Fe(II), we studied two systems in comparison: the ferritin from the hyperthermophilic archaeal anaerobe Pyrococcus furiosus (PfFtn) and the eukaryotic human H ferritin (HuHF). The results do not support either of the two paradigmatic models; instead they suggest a unifying mechanism in which the Fe(III)-O-Fe(III) unit resides in the ferroxidase center until it is sequentially displaced by Fe(II).

The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cornell, Thomas A.; Srivastava, Yogesh; Jauch, Ralf

Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understandmore » the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.« less

Ferritin L and Ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions.

PubMed

Ahmad, Shakil; Moriconi, Federico; Naz, Naila; Sultan, Sadaf; Sheikh, Nadeem; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

2013-01-01

Ferritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. Rats were administered turpentine-oil (TO) intramuscularly to induce a sterile abscess (acute-phase-model) and sacrificed at different time points. Immunohistochemistry was performed utilizing horse-reddish-peroxidise conjugated secondary antibody on 4μm thick section. Liver cytoplasmic and nuclear protein were used for Western blot analysis. By means of immunohistology, FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus.

Coordinating subdomains of ferritin protein cages with catalysis and biomineralization viewed from the C4 cage axes.

PubMed

Theil, Elizabeth C; Turano, Paola; Ghini, Veronica; Allegrozzi, Marco; Bernacchioni, Caterina

2014-06-01

Integrated ferritin protein cage function is the reversible synthesis of protein-caged, solid Fe2O3·H2O minerals from Fe(2+) for metabolic iron concentrates and oxidant protection; biomineral order differs in different ferritin proteins. The conserved 432 geometric symmetry of ferritin protein cages parallels the subunit dimer, trimer, and tetramer interfaces, and coincides with function at several cage axes. Multiple subdomains distributed in the self-assembling ferritin nanocages have functional relationships to cage symmetry such as Fe(2+) transport though ion channels (threefold symmetry), biomineral nucleation/order (fourfold symmetry), and mineral dissolution (threefold symmetry) studied in ferritin variants. On the basis of the effects of natural or synthetic subunit dimer cross-links, cage subunit dimers (twofold symmetry) influence iron oxidation and mineral dissolution. 2Fe(2+)/O2 catalysis in ferritin occurs in single subunits, but with cooperativity (n = 3) that is possibly related to the structure/function of the ion channels, which are constructed from segments of three subunits. Here, we study 2Fe(2+) + O2 protein catalysis (diferric peroxo formation) and dissolution of ferritin Fe2O3·H2O biominerals in variants with altered subunit interfaces for trimers (ion channels), E130I, and external dimer surfaces (E88A) as controls, and altered tetramer subunit interfaces (L165I and H169F). The results extend observations on the functional importance of structure at ferritin protein twofold and threefold cage axes to show function at ferritin fourfold cage axes. Here, conserved amino acids facilitate dissolution of ferritin-protein-caged iron biominerals. Biological and nanotechnological uses of ferritin protein cage fourfold symmetry and solid-state mineral properties remain largely unexplored.

Coordinating Subdomains of Ferritin Protein Cages with Catalysis and Biomineralization viewed from the C4 Cage Axes

PubMed Central

Theil, Elizabeth C.; Turano, Paola; Ghini, Veronica; Allegrozzi, Marco; Bernacchioni, Caterina

2014-01-01

Integrated ferritin protein cage function is the reversible synthesis of protein-caged, solid Fe2O3•H2O minerals from Fe2+, for metabolic iron concentrates and oxidant protection; biomineral order varies in different ferritin proteins. The conserved 4, 3, 2 geometric symmetry of ferritin protein cages, parallels subunit dimer, trimer and tetramer interfaces, and coincides with function at several cage axes. Multiple subdomains distributed in the self- assembling ferritin nanocages have functional relationships to cage symmetry such as Fe2+ transport though ion channels (3-fold symmetry), biomineral nucleation/order (4-fold symmetry) and mineral dissolution (3-fold symmetry) studied in ferritin variants. Cage subunit dimers (2-fold symmetry) influence iron oxidation and mineral dissolution, based on effects of natural or synthetic subunit dimer crosslinks. 2Fe2+/O2 catalysis in ferritin occurs in single subunits, but with cooperativity (n=3) that is possibly related to the structure/function of the ion channels, which are constructed from segments of 3 subunits. Here, we study 2Fe2+ + O2 protein catalysis (diferric peroxo formation) and dissolution of ferritin Fe2O3•H2O biominerals in variants with altered subunit interfaces for trimers (ion channels), E130I, and external dimer surfaces (E88A) as controls, and altered tetramer subunit interfaces (L165I and H169F). The results extend observations on the functional importance of structure at ferritin protein 2-fold and 3-fold cage axes to show function at ferritin 4-fold cage axes. Here, conserved amino acids facilitate dissolution of ferritin protein-caged iron biominerals. Biological and nanotechnological uses of ferritin protein cage 4-fold symmetry and solid state mineral properties remain largely unexplored. PMID:24504941

Rate of Iron Transfer Through the Horse Spleen Ferritin Shell Determined by the Rate of Formation of Prussian Blue and Fe-desferrioxamine Within the Ferritin Cavity

NASA Technical Reports Server (NTRS)

Zhang, Bo; Watt, Richard K.; Galvez, Natividad; Dominquez-Vera, Jose M.; Watt, Gerald D.

2005-01-01

Iron (2+ and 3+) is believed to transfer through the three-fold channels in the ferritin shell during iron deposition and release in animal ferritins. However, the rate of iron transit in and out through these channels has not been reported. The recent synthesis of [Fe(CN)(sub 6)](3-), Prussian Blue (PB) and desferrioxamine (DES) all trapped within the horse spleen ferritin (HoSF) interior makes these measurements feasible. We report the rate of Fe(2+) penetrating into the ferritin interior by adding external Fe(2+) to [Fe(CN)(sub 6)](3-) encapsulated in the HoSF interior and measuring the rate of formation of the resulting encapsulated PB. The rate at which Fe(2+) reacts with [Fe(CN)(sub 6)](3-) in the HoSF interior is much slower than the formation of free PB in solution and is proceeded by a lag period. We assume this lag period and the difference in rate represent the transfer of Fe(2+) through the HoSF protein shell. The calculated diffusion coefficient, D approx. 5.8 x 10(exp -20) square meters per second corresponds to the measured lag time of 10-20 s before PB forms within the HoSF interior. The activation energy for Fe(2+) transfer from the outside solution through the protein shell was determined to be 52.9 kJ/mol by conducting the reactions at 10 to approximately 40 C. The reaction of Fe(3+) with encapsulated [Fe(CN)6](4-) also readily forms PB in the HoSF interior, but the rate is faster than the corresponding Fe(2+) reaction. The rate for Fe(3+) transfer through the ferritin shell was confirmed by measuring the rate of the formation of Fe-DES inside HoSF and an activation energy of 58.4 kJ/mol was determined. An attempt was made to determine the rate of iron (2+ and 3+) transit out from the ferritin interior by adding excess bipyridine or DES to PB trapped within the HoSF interior. However, the reactions are slow and occur at almost identical rates for free and HoSF-encapsulated PB, indicating that the transfer of iron from the interior through the

Molecular Characterization and Functional Analysis of a Ferritin Heavy Chain Subunit from the Eri-Silkworm, Samia cynthia ricini

PubMed Central

Yu, Hai-Zhong; Zhang, Shang-Zhi; Ma, Yan; Fei, Dong-Qiong; Li, Bing; Yang, Li-Ang; Wang, Jie; Li, Zhen; Muhammad, Azharuddin; Xu, Jia-Ping

2017-01-01

Ferritins are conserved iron-binding proteins that are primarily involved in iron storage, detoxification and the immune response. Despite the importance of ferritin in organisms, little is known about their roles in the eri-silkworm (Samia cynthia ricini). We previously identified a ferritin heavy chain subunit named ScFerHCH in the S. c. ricini transcriptome database. The full-length S. c. ricini ferritin heavy chain subunit (ScFerHCH) was 1863 bp and encoded a protein of 231 amino acids with a deduced molecular weight of 25.89 kDa. Phylogenetic analysis revealed that ScFerHCH shared a high amino acid identity with the Bombyx mori and Danaus plexippus heavy chain subunits. Higher ScFerHCH expression levels were found in the silk gland, fat body and midgut of S. c. ricini by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Injection of Staphylococcus aureus and Pseudomonas aeruginosa was associated with an upregulation of ScFerHCH in the midgut, fat body and hemolymph, indicating that ScFerHCH may contribute to the host’s defense against invading pathogens. In addition, the anti-oxidation activity and iron-binding capacity of recombinant ScFerHCH protein were examined. Taken together, our results suggest that the ferritin heavy chain subunit from eri-silkworm may play critical roles not only in innate immune defense, but also in organismic iron homeostasis. PMID:29036914

Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

NASA Astrophysics Data System (ADS)

Balejcikova, Lucia; Strbak, Oliver; Baciak, Ladislav; Kovac, Jozef; Masarova, Marta; Krafcik, Andrej; Frollo, Ivan; Dobrota, Dusan; Kopcansky, Peter

2017-04-01

Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation.

Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization

PubMed Central

Buisson, Christophe; Daou, Nadine; Kallassy, Mireille; Lereclus, Didier; Arosio, Paolo; Bou-Abdallah, Fadi; Nielsen Le Roux, Christina

2014-01-01

In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis. PMID:24550730

PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

EPA Science Inventory

PLASMID DNA DAMAGE CAOUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

ABSTRACT

Both dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) release iron from human liver ferritin (HLF) with or without the presence of ascorbic acid. ...

Enhanced Iron Uptake of Saccharomyces cerevisiae by Heterologous Expression of a Tadpole Ferritin Gene

PubMed Central

Shin, Young-Mi; Kwon, Tae-Ho; Kim, Kyung-Suk; Chae, Keon-Sang; Kim, Dae-Hyuk; Kim, Jae-Ho; Yang, Moon-Sik

2001-01-01

We genetically engineered Saccharomyces cerevisiae to express ferritin, a ubiquitous iron storage protein, with the major heavy-chain subunit of tadpole ferritin. A 450-kDa ferritin complex can store up to 4,500 iron atoms in its central cavity. We cloned the tadpole ferritin heavy-chain gene (TFH) into the yeast shuttle vector YEp352 under the control of a hybrid alcohol dehydrogenase II and glyceraldehyde-3-phosphate dehydrogenase promoter. We confirmed transformation and expression by Northern blot analysis of the recombinant yeast, by Western blot analysis using an antibody against Escherichia coli-expressed TFH, and with Prussian blue staining that indicated that the yeast-expressed tadpole ferritin was assembled into a complex that could bind iron. The recombinant yeast was more iron tolerant in that 95% of transformed cells, but none of the recipient strain cells, could form colonies on plates containing 30 mM ferric citrate. The cell-associated concentration of iron was 500 μg per gram (dry cell weight) of the recombinant yeast but was 210 μg per gram (dry cell weight) in the wild type. These findings indicate that the iron-carrying capacity of yeast is improved by heterologous expression of tadpole ferritin and suggests that this approach may help relieve dietary iron deficiencies in domesticated animals by the use of the engineered yeast as a feed and food supplement. PMID:11229922

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia. (b... that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron...

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

PubMed

Jalalzadeh, M; Shekari, E; Mirzamohammadi, F; Ghadiani, M H

2012-05-01

Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

Factors Associated With Elevated Blood Lead Levels in Children.

PubMed

Chaudhary, Sakshi; Firdaus, Uzma; Ali, Syed Manazir; Mahdi, Abbas Ali

2018-01-15

To determine the prevalence and correlates of elevated blood lead level in children (6-144 months) of Aligarh. A hospital-based cross-sectional study was conducted. Venous blood was obtained for lead estimation and a structured questionnaire was filled. A total of 260 children were enrolled. The prevalence of elevated blood lead level was 44.2%, seen mostly in children below 5 years of age. Old and deteriorating wall paints at home was found to be significantly associated with elevated levels. Lead-based house paints are potential source of lead exposure. Meticulous renovation and painting of the walls with safe paints is desirable.

Multiple ferritins are vital to successful blood feeding and reproduction of the hard tick Haemaphysalis longicornis.

PubMed

Galay, Remil Linggatong; Aung, Kyaw Min; Umemiya-Shirafuji, Rika; Maeda, Hiroki; Matsuo, Tomohide; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Suzuki, Hiroshi; Xuan, Xuenan; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2013-05-15

Ticks are obligate hematophagous parasites and important vectors of diseases. The large amount of blood they consume contains great quantities of iron, an essential but also toxic element. The function of ferritin, an iron storage protein, and iron metabolism in ticks need to be further elucidated. Here, we investigated the function a newly identified secreted ferritin from the hard tick Haemaphysalis longicornis (HlFER2), together with the previously identified intracellular ferritin (HlFER1). Recombinant ferritins, expressed in Escherichia coli, were used for anti-serum preparation and were also assayed for iron-binding activity. RT-PCR and western blot analyses of different organs and developmental stages of the tick during blood feeding were performed. The localization of ferritins in different organs was demonstrated through an indirect immunofluorescent antibody test. RNA interference (RNAi) was performed to evaluate the importance of ferritin in blood feeding and reproduction of ticks. The midgut was also examined after RNAi using light and transmission electron microscopy. RT-PCR showed differences in gene expression in some organs and developmental stages. Interestingly, only HlFER2 was detected in the ovary during oviposition and in the egg despite the low mRNA transcript. RNAi induced a reduction in post-blood meal body weight, high mortality and decreased fecundity. The expression of vitellogenin genes was affected by silencing of ferritin. Abnormalities in digestive cells, including disrupted microvilli, and alteration of digestive activity were also observed. Taken altogether, our results show that the iron storage and protective functions of ferritin are crucial to successful blood feeding and reproduction of H. longicornis.

Potentiometric assessment of iron release during ferritin reduction by exogenous agents.

PubMed

Vladimirova, Lilia S; Kochev, Valery K

2010-09-01

This work studied the possibilities for quantitative determination of iron mobilization in connection with ferritin reduction by ascorbic acid (vitamin C) and sodium dithionite in vitro. The iron storage protein was incubated with an excess of reductant in aerobic conditions in the absence of complexing agents in the medium. The release of Fe(2+) was let to go to completion, and the overall content of Fe(2+) in the solution was evaluated with the aid of potentiometric titration using Ce(4+) as an oxidizing titrant. Results suggest a moderate iron efflux under the influence of the chosen reducing agents. Although such a reduction of the protein mineral core by dihydroxyfumarate contributes greatly to the iron mobilization, ferritin behavior with vitamin C and dithionite seems to be different. Although redox properties of dihydroxyfumarate are determined by hydroxyl groups similar to those of ascorbic acid, the two compounds differ significantly in structure, and this could be the basis for an explanation of the specificities in their interaction with ferritin. As revealed by the study, potentiometric titration promises to be a reliable tool for evaluation of the amount of Fe(2+) present in the solution as a result of the reduction of the ferritin's mineral core. 2010 Elsevier Inc. All rights reserved.

Structural characterization of encapsulated ferritin provides insight into iron storage in bacterial nanocompartments

PubMed Central

He, Didi; Hughes, Sam; Vanden-Hehir, Sally; Georgiev, Atanas; Altenbach, Kirsten; Tarrant, Emma; Mackay, C Logan; Waldron, Kevin J; Clarke, David J; Marles-Wright, Jon

2016-01-01

Ferritins are ubiquitous proteins that oxidise and store iron within a protein shell to protect cells from oxidative damage. We have characterized the structure and function of a new member of the ferritin superfamily that is sequestered within an encapsulin capsid. We show that this encapsulated ferritin (EncFtn) has two main alpha helices, which assemble in a metal dependent manner to form a ferroxidase center at a dimer interface. EncFtn adopts an open decameric structure that is topologically distinct from other ferritins. While EncFtn acts as a ferroxidase, it cannot mineralize iron. Conversely, the encapsulin shell associates with iron, but is not enzymatically active, and we demonstrate that EncFtn must be housed within the encapsulin for iron storage. This encapsulin nanocompartment is widely distributed in bacteria and archaea and represents a distinct class of iron storage system, where the oxidation and mineralization of iron are distributed between two proteins. DOI: http://dx.doi.org/10.7554/eLife.18972.001 PMID:27529188

Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

PubMed Central

Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

2009-01-01

Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

Nanophase iron phosphate, iron arsenate, iron vanadate, and iron molybdate minerals synthesized within the protein cage of ferritin.

PubMed

Polanams, Jup; Ray, Alisha D; Watt, Richard K

2005-05-02

Nanoparticles of iron phosphate, iron arsenate, iron molybdate, and iron vanadate were synthesized within the 8 nm interior of ferritin. The synthesis involved reacting Fe(II) with ferritin in a buffered solution at pH 7.4 in the presence of phosphate, arsenate, vanadate, or molybdate. O2 was used as the oxidant to deposit the Fe(III) mineral inside ferritin. The rate of iron incorporation into ferritin was stimulated when oxo-anions were present. The simultaneous deposition of both iron and the oxo-anion was confirmed by elemental analysis and energy-dispersive X-ray analysis. The ferritin samples containing iron and one of the oxo-anions possessed different UV/vis spectra depending on the anion used during mineral formation. TEM analysis showed mineral cores with approximately 8 nm mineral particles consistent with the formation of mineral phases inside ferritin.

Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy.

PubMed

Mast, Alan E; Schlumpf, Karen S; Wright, David J; Johnson, Bryce; Glynn, Simone A; Busch, Michael P; Olbina, Gordana; Westerman, Mark; Nemeth, Elizabeta; Ganz, Tomas

2013-08-01

Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (≥3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized ≥4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (>45.7 ng/mL) or decreasing hepcidin and low ferritin (>26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (>26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone. Clinicaltrials.gov identifier: NCT00097006.

Stress and transcriptional regulation of tick ferritin HC.

PubMed

Mulenga, A; Simser, J A; Macaluso, K R; Azad, A F

2004-08-01

We previously identified a partial Dermacentor variabilis cDNA encoding ferritin HC (HC) subunit homolog (DVFER) that was differentially upregulated in Rickettsia montanensis infected ticks (Mulenga et al., 2003a). We have used rapid amplification of cDNA ends to clone full-length DVFER cDNA and its apparent ortholog from the wood tick, D. andersoni (DAFER), both of which show high sequence similarity to vertebrate than insect ferritin. Both DVFER and DAFER contain the stem-loop structure of a putative iron responsive element in the 5' untranslated region (nucleotide positions, 16-42) and the feroxidase centre loop typical for vertebrate ferritin HC subunits. Quantitative Western and Northern blotting analyses of protein and RNA from unfed and partially fed whole tick as well as dissected tick tissues demonstrated that DVFER is constitutively and ubiquitously expressed. Based on densitometric analysis of detected protein and mRNA bands, DVFER is predominantly expressed in the midgut, and to a lesser extent in the salivary glands, ovary and fatbody. Sham treatment (mechanical injury) and Escherichia coli challenge of D. variabilis ticks stimulated statistically significant (approximately 1.5- and approximately 3.0-fold, respectively) increases in DVFER mRNA abundance over time point matched naive control ticks. These data suggest that DVFER mRNA is nonspecifically up regulated in response to mechanical injury or bacterial infection induced stress.

Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

PubMed Central

Zarjou, Abolfazl; Bolisetty, Subhashini; Joseph, Reny; Traylor, Amie; Apostolov, Eugene O.; Arosio, Paolo; Balla, Jozsef; Verlander, Jill; Darshan, Deepak; Kuhn, Lukas C.; Agarwal, Anupam

2013-01-01

Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule–specific FtH-knockout mice (FtHPT–/– mice). FtHPT–/– mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtHPT–/– mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase–associated lipocalin, hemopexin, and transferrin were increased in FtHPT–/– mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI. PMID:24018561

Serum ferritin is a different predictor from transfusion history for allogeneic transplantation outcome in patients with severe aplastic anemia.

PubMed

Zhang, Xiaoyu; Shi, Yuanyuan; Huang, Yong; Zhang, Guixin; He, Yi; Jiang, Erlie; Wei, Jialin; Yang, Donglin; Ma, Qiaoling; Zhang, Rongli; Zhai, Weihua; Feng, Sizhou; Han, Mingzhe

2018-06-01

Severe aplastic anemia (SAA) patients receive more red blood cell (RBC) transfusions as supportive management. We aim to clarify the associations between transfusion history or pre-transplantation serum ferritin (SF) and the overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) among SAA patients. We retrospectively investigated 96 SAA patients undergoing allo-HSCT, and grouped them according to pre-transplantation duration. Pre-transplantation SF, transfused units and other iron-related parameters were collected. Comparisons in transplantation outcomes and complications were made in groups with different SF levels and different transfusion histories. Among the 96 SAA patients, 45 patients received transplantation within 2 months after diagnosis (short-term pre-transplantation period), and the rest of the patients had long-term pre-transplantation treatment. Among the patients with short-term pre-transplantation treatment, a higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF also predicted a trend in incidence of higher bloodstream infection (p = 0.108). Significant correlations were observed between pre-transplantation SF and infection incidence, as well as transfusion history. However, for patients with longer pre-transplantation duration, transfusion history was associated with worse outcome (p = 0.026), in terms of higher incidence of acute graft versus host disease (p = 0.048). High SF was only significantly associated with prolonged RBC transfusion dependence post-transplantation (p = 0.044). Transfusion history was a stronger predictor of outcome than SF in patients undergoing transplantation more than 2 months after diagnosis.

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

PubMed

Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

2008-08-01

Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review.

PubMed

Daru, J; Allotey, J; Peña-Rosas, J P; Khan, K S

2017-06-01

The aim of this review was to understand the landscape of serum ferritin in diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron deficiency in pregnancy is a major public health problem leading to the development of anaemia. Reducing the global prevalence of anaemia in women of reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the gold standard test for iron deficiency but requires an invasive procedure; therefore, serum ferritin is the most clinically useful test. We undertook a systematic search of electronic databases and trial registers from inception to January 2016. Studies of iron or micronutrient supplementation in pregnancy with pre-defined serum ferritin thresholds were included. Two independent reviewers selected studies, extracted data and assessed quality. There were 76 relevant studies mainly of observational study design (57%). The most commonly used thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and <15 ng mL -1 (68%). Most primary studies provided no justification for the choice of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by expert consensus in a guideline development process. There were five studies (7%) using a serum ferritin threshold defining iron deficiency derived from primary studies of bone marrow aspiration. Unified international thresholds of iron deficiency for women throughout pregnancy are required for accurate assessments of the global disease burden and for evaluating effectiveness of interventions addressing this problem. © 2017 World Health Organization licensed by Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration.

PubMed

Finazzi, Dario; Arosio, Paolo

2014-10-01

Iron is an abundant transition metal that is essential for life, being associated with many enzyme and oxygen carrier proteins involved in a variety of fundamental cellular processes. At the same time, the metal is potentially toxic due to its capacity to engage in the catalytic production of noxious reactive oxygen species. The control of iron availability in the cells is largely dependent on ferritins, ubiquitous proteins with storage and detoxification capacity. In mammals, cytosolic ferritins are composed of two types of subunits, the H and the L chain, assembled to form a 24-mer spherical cage. Ferritin is present also in mitochondria, in the form of a complex with 24 identical chains. Even though the proteins have been known for a long time, their study is a very active and interesting field yet. In this review, we will focus our attention to mammalian cytosolic and mitochondrial ferritins, describing the most recent advancement regarding their storage and antioxidant function, the effects of their genetic mutations in human pathology, and also the possible involvement in non-iron-related activities. We will also discuss recent evidence connecting ferritins and the toxicity of iron in a set of neurodegenerative disorder characterized by focal cerebral siderosis.

The usage of phage mini-antibodies as a means of detecting ferritin concentration in animal blood serum.

PubMed

Staroverov, Sergey A; Volkov, Alexei A; Fomin, Alexander S; Laskavuy, Vladislav N; Mezhennyy, Pavel V; Kozlov, Sergey V; Larionov, Sergey V; Fedorov, Michael V; Dykman, Lev A; Guliy, Olga I

2015-01-01

Mini-antibodies that have specific ferritin response have been produced for the first time using sheep's phage libraries (Griffin.1, Medical Research Council, Cambridge, UK). Produced phage antibodies were used for the first time for the development of diagnostic test kits for ferritin detection in the blood of cattle. The immunodot assay with secondary biospecific labeling is suggested as means of ferritin detection in cow blood serum (antiferritin phage antibodies and rabbit antiphage antibodies conjugated with different labels). Сolloidal gold, gold nanoshells, and horse reddish peroxidase used as labels have shown a similar response while detecting concentration of ferritin (0.2 mg/mL). It is shown that the method of solid-phase immunoassay with a visual view of the results allows determination of the minimum concentration of ferritin in the blood of cows at 0.225 g/mL.

ELEVATED GAMMA-AMINOBUTYRIC ACID LEVELS IN CHRONIC SCHIZOPHRENIA

PubMed Central

Öngür, Dost; Prescot, Andrew P.; McCarthy, Julie; Cohen, Bruce M.; Renshaw, Perry F.

2010-01-01

Background Despite widely-replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy controls in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC). Methods 21 schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy controls (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7cc voxels and analyzed using LCModel. Results We found elevations in GABA/Cr in the schizophrenia group compared with controls (F(1,65)=4.149, p=0.046) in both brain areas (15.5% elevation in ACC, 11.9% in POC). We also found a positive correlation between GABA/Cr and Glu/Cr which was not accounted for by %GM or brain region. Conclusions We found elevated GABA/Cr in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. PMID:20598290

Effect of chaotropes on the kinetics of iron release from ferritin by flavin nucleotides.

PubMed

Johnson, Lindsay E; Wilkinson, Tyler; Arosio, Paolo; Melman, Artem; Bou-Abdallah, Fadi

2017-12-01

Ferritins are ubiquitous multi-subunit iron storage and detoxification proteins that play a critical role in iron homeostasis. Ferrous ions that enter the protein's shell through hydrophilic channels are rapidly oxidized at dinuclear centers on the H-subunit before transfer to the protein's cavity for storage. The mechanisms of iron loading have been extensively studied, but little is known about iron mobilization. Fe(III) reduction can occur via rapid reduction by suitable reducing agents followed by chelation of Fe(II) ions or via direct and slow Fe(III) chelation. Here, the iron release kinetics from ferritin by FMNH 2 in the presence of various chaotropic agents are studied and their in-vivo physiological significance discussed. The iron release kinetics from horse and human ferritins by FMNH 2 were monitored at 522nm where the Fe(II)-bipyridine complex absorbs. The experiments were performed in the presence of different concentrations of three chaotropic agents, urea, guanidine HCl, and triton. Under our experimental conditions, iron reductive mobilization by the non-enzymatic FMN/NAD(P)H system is limited by the concentration of FMNH 2 and is independent on the type or amount of chaotropes present. Diffusion of FMNH 2 through the ferritin pores is an unlikely mechanism for ferritin iron reduction. An iron mobilization mechanism involving rapid electron transfer through the protein shell is discussed. Caution must be exercised when interpreting the kinetics of iron mobilization from ferritin using the FMN/NAD(P)H system. The kinetics are highly dependent on the amount of dissolved oxygen and the concentration of reagents used. Copyright © 2017 Elsevier B.V. All rights reserved.

The hepcidin gene promoter nc.-1010C > T; -582A > G haplotype modulates serum ferritin in individuals carrying the common H63D mutation in HFE gene.

PubMed

Silva, Bruno; Pita, Lina; Gomes, Susana; Gonçalves, João; Faustino, Paula

2014-12-01

Hereditary hemochromatosis is an autosomal recessive disorder characterized by severe iron overload. It is usually associated with homozygosity for the HFE gene mutation c.845G > A; p.C282Y. However, in some cases, another HFE mutation (c.187C > G; p.H63D) seems to be associated with the disease. Its penetrance is very low, suggesting the possibility of other iron genetic modulators being involved. In this work, we have screened for HAMP promoter polymorphisms in 409 individuals presenting normal or increased serum ferritin levels together with normal or H63D-mutated HFE genotypes. Our results show that the hepcidin gene promoter TG haplotype, originated by linkage of the nc.-1010C > T and nc.-582A > G polymorphisms, is more frequent in the HFE_H63D individuals presenting serum ferritin levels higher than 300 μg/L than in those presenting the HFE_H63D mutation but with normal serum ferritin levels or in the normal control group.Moreover, it was observed that the TG haplotype was associated to increased serum ferritin levels in the overall pool of HFE_H63D individuals. Thus, our data suggest that screening for these polymorphisms could be of interest in order to explain the phenotype. However, this genetic condition seems to have no clinical significance.

Iron in Parkinson disease, blood diseases, malaria and ferritin

NASA Astrophysics Data System (ADS)

Bauminger, E. R.; Nowik, I.

1998-12-01

The concentration of iron in Substantia nigra, the part of the brain which is involved in Parkinson disease, has been found by Mössbauer spectroscopy (MS) to be ~ 160 μg/g wet tissue and ~ 670 μg/g dry weight, both in control and Parkinson samples. All the iron observed by MS in these samples is ferritin-like iron. In several blood diseases, large amounts of ferritin-like iron have been observed in red blood cells. Desferral removed iron from serum, but not from red blood cells. The iron compound in the malarial pigment of human blood infected by P. falciparum was found to be hemin-like, whereas the pigment iron in rats infected by P. berghei was different from any known iron porphyrin.

Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins

PubMed Central

Venn-Watson, Stephanie K.; Parry, Celeste; Baird, Mark; Stevenson, Sacha; Carlin, Kevin; Daniels, Risa; Smith, Cynthia R.; Jones, Richard; Wells, Randall S.; Ridgway, Sam; Jensen, Eric D.

2015-01-01

Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0) compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001). Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome. PMID:26200116

Ferritin conjugates as specific magnetic labels. Implications for cell separation.

PubMed Central

Odette, L L; McCloskey, M A; Young, S H

1984-01-01

Concanavalin A coupled to the naturally occurring iron storage protein ferritin is used to label rat erythrocytes and increase the cells' magnetic susceptibility. Labeled cells are introduced into a chamber containing spherical iron particles and the chamber is placed in a uniform 5.2 kG (gauss) magnetic field. The trajectory of cells in the inhomogeneous magnetic field around the iron particles and the polar distributions of cells bound to the iron particles compare well with the theoretical predictions for high gradient magnetic systems. On the basis of these findings we suggest that ferritin conjugated ligands can be used for selective magnetic separation of labeled cells. Images FIGURE 2 PMID:6743752

Elevated gamma-aminobutyric acid levels in chronic schizophrenia.

PubMed

Ongür, Dost; Prescot, Andrew P; McCarthy, Julie; Cohen, Bruce M; Renshaw, Perry F

2010-10-01

Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in the anterior cingulate cortex and parieto-occipital cortex. Twenty-one schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy control subjects (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7-mL voxels and analyzed using LCModel. We found elevations in GABA/creatine in the schizophrenia group compared with control subjects [F(1,65) = 4.149, p = .046] in both brain areas (15.5% elevation in anterior cingulate cortex, 11.9% in parieto-occipital cortex). We also found a positive correlation between GABA/creatine and glutamate/creatine, which was not accounted for by % GM or brain region. We found elevated GABA/creatinine in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Identification and characterization of a ferritin gene and its product from the multicellular green alga Ulva pertusa.

PubMed

Morimoto, Shin-Ichiro; Masuda, Taro; Sugihara, Itaru; Toyohara, Haruhiko

2012-01-01

Iron is an essential element for virtually all kingdoms of life, and especially for primary producers in ocean ecosystems. To date, the molecular mechanism of iron utilization by macroalgae remains largely unknown. To elucidate the strategy of iron acquisition and storage in macroalgae, we focused on the function of the iron storage protein ferritin in the sea lettuce, Ulva pertusa, which has abundant iron content. Judging from the primary structure, U. pertusa ferritin (UpFer) can be classified as a land-plant-type ferritin, which is usually found in plastids. The gene of UpFer was expressed in the peripheral, central and rhizoid parts. Western blot analysis showed that UpFER was present and functioned in processed 26- and 22-kDa forms. Furthermore, recombinant UpFER had iron incorporation activity comparable to other ferritins. These results suggest that ferritin also functions as an iron storage protein as in unicellular algae and land plants.

Ferritin cage for encapsulation and delivery of bioactive nutrients: From structure, property to applications.

PubMed

Zang, Jiachen; Chen, Hai; Zhao, Guanghua; Wang, Fudi; Ren, Fazheng

2017-11-22

Ferritin is a class of naturally occurring iron storage proteins, which is distributed widely in animal, plant, and bacteria. It usually consists of 24 subunits that form a hollow protein shell with high symmetry. One holoferritin molecule can store up to 4500 iron atom within its inner cavity, and it becomes apoferritin upon removal of iron from the cavity. Recently, scientists have subverted these nature functions and used reversibly self-assembled property of apoferritin cage controlled by pH for the encapsulation and delivery of bioactive nutrients or anticancer drug. In all these cases, the ferritin cages shield their cargo from the influence of external conditions and provide a controlled microenvironment. More importantly, upon encapsulation, ferritin shell greatly improved the water solubility, thermal stability, photostability, and cellular uptake activity of these small bioactive compounds. This review aims to highlight recent advances in applications of ferritin cage as a novel vehicle in the field of food science and nutrition. Future outlooks are highlighted with the aim to suggest a research line to follow for further studies.

Ferritin glycosylated by chitosan as a novel EGCG nano-carrier: Structure, stability, and absorption analysis.

PubMed

Yang, Rui; Liu, Yuqian; Gao, Yunjing; Wang, Yongjin; Blanchard, Chris; Zhou, Zhongkai

2017-12-01

Ferritin is a shell-like carrier protein with an 8nm diameter cavity which endows a natural space to encapsulate food and drug components. In this work, phytoferritin was unprecedentedly glycosylated by chitosan to fabricate ferritin-chitosan Maillard reaction products (FCMPs) (grafting degree of 26.17%, 24h, 55°C). Results indicated that the amide I and II bands of ferritin were altered due to the chitosan grafting, whereas the ferritin spherical structure were retained. Simulated digestion analysis showed that the FCMPs were more resistant to pepsin and trypsin digestion as compared with ferritin alone. Furthermore, FCMPs were employed as carrier to encapsulate epigallocatechin gallate (EGCG) molecules with an encapsulation ratio of 12.87% (w/w), and the resulting FCMPs-EGCG complexes showed a slow release of EGCG in simulated gastrointestinal tract. Interestingly, different types of food components displayed different effects in EGCG release behavior from the FCMPs, wherein proanthocyanidin, milk and soy protein inhibited the EGCG release. In addition, the absorption of EGCG encapsulated in FCMPs in Caco-2 monolayer model was significantly improved as compared with free EGCG. This work provides a novel nano-vehicle for fabricating core-shell systems in food and drug delivery domain. Copyright © 2017 Elsevier B.V. All rights reserved.

A combination of serum iron, ferritin and transferrin predicts outcome in patients with intracerebral hemorrhage

PubMed Central

Yang, Guang; Hu, Rong; Zhang, Chao; Qian, Christopher; Luo, Qian-Qian; Yung, Wing-Ho; Ke, Ya; Feng, Hua; Qian, Zhong-Ming

2016-01-01

Association of a high-serum ferritin with poor outcome showed that iron might play a detrimental role in the brain after intracerebral hemorrhage (ICH). Here, we investigated changes in serum iron, ferritin, transferrin (Tf) and ceruloplasmin (CP) in patients with ICH (n = 100) at day 1 (admission), 3, 7, 14 and 21 and those in control subjects (n = 75). The hematoma and edema volumes were also determined in ICH-patients on admission and at day 3. The Modified Rankin Scale (mRS) of 59 patients was ≥3 (poor outcome) and 41 < 3 (good outcome) at day 90. Serum ferritin was significantly higher and serum iron and Tf markedly lower in patients with poor-outcome than the corresponding values in patients with good-outcome at day 1 to 7 and those in the controls. There was a significant positive correlation between serum ferritin and relative edema volume or ratio at day 1 and 3 and hematoma volume at day 1 (n = 28), and a negative correlation between serum iron or Tf and hematoma volume at day 1 (n = 100). We concluded that not only increased serum ferritin but also reduced serum iron and Tf are associated with outcome as well as hematoma volume. PMID:26898550

Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

PubMed

Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

2012-01-01

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Molecular characterization of two ferritins of the scallop Argopecten purpuratus and gene expressions in association with early development, immune response and growth rate.

PubMed

Coba de la Peña, Teodoro; Cárcamo, Claudia B; Díaz, María I; Brokordt, Katherina B; Winkler, Federico M

2016-08-01

Ferritin is involved in several iron homoeostasis processes in molluscs. We characterized two ferritin homologues and their expression patterns in association with early development, growth rate and immune response in the scallop Argopecten purpuratus, a species of economic importance for Chile and Peru. Two ferritin subunits (Apfer1 and Apfer2) were cloned. Apfer1 cDNA is a 792bp clone containing a 516bp open reading frame (ORF) that corresponds to a novel ferritin subunit in A. purpuratus. Apfer2 cDNA is a 681bp clone containing a 522bp ORF that corresponds to a previously sequenced EST. A putative iron responsive element (IRE) was identified in the 5'-untranslated region of both genes. The deduced protein sequences of both cDNAs possessed the motifs and domains characteristic of functional ferritin subunits. Both genes showed differential expression patterns at tissue-specific and early development stage levels. Apfer1 expression level increased 40-fold along larval developmental stages, decreasing markedly after larval settlement. Apfer1 expression in mantle tissue was 2.8-fold higher in fast-growing than in slow-growing scallops. Apfer1 increased 8-fold in haemocytes 24h post-challenge with the bacterium Vibrio splendidus. Apfer2 expression did not differ between fast- and slow-growing scallops or in response to bacterial challenge. These results suggest that Apfer1 and Apfer2 may be involved in iron storage, larval development and shell formation. Apfer1 expression may additionally be involved in immune response against bacterial infections and also in growth; and thus would be a potential marker for immune capacity and for fast growth in A. purpuratus. Copyright © 2016 Elsevier Inc. All rights reserved.

Morphology of the ferritin iron core by aberration corrected scanning transmission electron microscopy

NASA Astrophysics Data System (ADS)

Jian, Nan; Dowle, Miriam; Horniblow, Richard D.; Tselepis, Chris; Palmer, Richard E.

2016-11-01

As the major iron storage protein, ferritin stores and releases iron for maintaining the balance of iron in fauna, flora, and bacteria. We present an investigation of the morphology and iron loading of ferritin (from equine spleen) using aberration-corrected high angle annular dark field scanning transmission electron microscopy. Atom counting method, with size selected Au clusters as mass standards, was employed to determine the number of iron atoms in the nanoparticle core of each ferritin protein. Quantitative analysis shows that the nuclearity of iron atoms in the mineral core varies from a few hundred iron atoms to around 5000 atoms. Moreover, a relationship between the iron loading and iron core morphology is established, in which mineral core nucleates from a single nanoparticle, then grows along the protein shell before finally forming either a solid or hollow core structure.

Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells

NASA Astrophysics Data System (ADS)

Geninatti Crich, S.; Cadenazzi, M.; Lanzardo, S.; Conti, L.; Ruiu, R.; Alberti, D.; Cavallo, F.; Cutrin, J. C.; Aime, S.

2015-04-01

In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation. Electronic supplementary information (ESI) available: Competition studies with free apoferritin, Fig. S1; APO-FITC intracellular distribution by

Flowering responses of insect-pollinated plants to elevated CO{sub 2} levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cushman, J.H.; Koch, G.W.; Chiariello, N.R.

1995-06-01

Elevated atmospheric CO{sub 2} concentrations have been predicted or shown to substantially influence plants, communities and ecosystems in a variety of ways. Here, we examined the effects of elevated CO{sub 2} levels on the timing and magnitude of flowering for two insect-pollinated annual plant species in a serpentine grassland. We focused on Lasthenia californica and Linanthus parviflorus and addressed three questions: (1) Do elevated CO{sub 2} levels influence flowering phenologies and is this species specific? (2) Do elevated CO{sub 2} levels affect flower production and is this due to altered numbers of individuals, flowers per plant, or both? and (3)more » Are effects on flowering due to elevated CO{sub 2} levels per se or changes in environmental conditions associated with methods used to manipulate CO{sub 2} levels? To address these questions, we used the ecosystem experiment at Stanford University`s Jasper Ridge Biological Preserve (San Mateo Co., CA). This system consists of 20 open-topped chambers - half receiving ambient CO{sub 2} (360 ppm) and half receiving elevated CO{sub 2} (720 ppm) - and 10 untreated plots serving as chamber controls. Results from the 1994 season demonstrated that there were species-specific responses to elevated CO{sub 2} levels and the field chambers. For Lasthenia californica, elevated CO{sub 2} per se did not affect relative abundance, inflorescence production, or phenology, but chambers did significantly increase inflorescence production and extend the duration of flowering. For Linanthus parviflorus, elevated CO{sub 2} levels significantly increased relative abundance and flower production, and extended the flowering period slightly, while the chambers significantly decreased flower production early in the season and increased it later in the season.« less

Creation of energetic biothermite inks using ferritin liquid protein

NASA Astrophysics Data System (ADS)

Slocik, Joseph M.; McKenzie, Ruel; Dennis, Patrick B.; Naik, Rajesh R.

2017-04-01

Energetic liquids function mainly as fuels due to low energy densities and slow combustion kinetics. Consequently, these properties can be significantly increased through the addition of metal nanomaterials such as aluminium. Unfortunately, nanoparticle additives are restricted to low mass fractions in liquids because of increased viscosities and severe particle agglomeration. Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to overcoming low mass fractions of nanoparticles, producing stable nanoparticle dispersions and simultaneously offering a source of oxidizing agents for combustion of reactive nanomaterials. Here, we use iron oxide-loaded ferritin proteins to create a stable and highly energetic liquid composed of aluminium nanoparticles and ferritin proteins for printing and forming 3D shapes and structures. In total, this bioenergetic liquid exhibits increased energy output and performance, enhanced dispersion and oxidation stability, lower activation temperatures, and greater processability and functionality.

Cross-links (XL) and Zn action in ferritin related to an H-specific site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yablonski, M.J.; Theil, E.C.

1991-03-15

Zn and subunit cross-links (F{sub 2}DNB) alter ferritin iron core formation in vivo and in vitro; the effect is observed in ferritins composed of two subunit types (H and L). Protein coats from sheep spleen ferritin (SSF) ({plus minus} XL), a model for a protein with H and L subunits (1:1), and horse spleen ferritin (HSF), a model for H deficient protein were reconstituted with Fe{sup 2+}, {plus minus} Zn, at pH 6.1 and 7.0 in order to investigate the effects of Zn and XLs on H and L subunits. Core formation was measured both as {Delta}A{sub 420} and themore » accessibility of Fe{sup 2+} to 1,10-phenanthroline. At pH 6.1, Zn decreased the {Delta}A{sub 420} in 1 min {ge} 87X (SSF) or 15X (HSF). XLs ({plus minus}Zn) decreased {Delta}A{sub 420} at 1 min similarly; at pH 7.0, Zn reduced {Delta}A{sub 420} at 1 min in SSF 3X with no effect on HSF. At both values of pH, Zn increased accessibility equally for SSF and HSF. The data indicate that : Zn has different effects on core formation measured as {Delta}A{sub 420} at 1 min or Fe{sup 2+} entry into ferritin; cross-links and Zn affects a common site involved in core formation; and Zn affects an H subunit-specific site which may involve histidine.« less

Association of Increased Serum Ferritin With Impaired Muscle Strength/Quality in Hemodialysis Patients.

PubMed

Nakagawa, Chie; Inaba, Masaaki; Ishimura, Eiji; Yamakawa, Tomoyuki; Shoji, Shigeichi; Okuno, Senji

2016-07-01

We reported previously that muscle quality and muscle strength provide clinically relevant predictors for better survival in hemodialysis patients. Iron overload might impair muscle function by its accumulation in muscle in such patients. Serum ferritin, a marker for body iron store, was examined for its association with handgrip strength (HGS) and muscle quality which was defined as the ratio of HGS to arm lean mass measured with dual-energy X-ray absorptiometry. In 300 Japanese hemodialysis patients, age, hemodialysis duration, body mass index, and serum albumin were 58.0 ±12.0 (mean ± standard deviation) years, 4.2 (1.8-10.4) (median [25th-75th percentile]) years, 20.4 ± 2.8 kg/m(2), 4.0 ± 0.3 g/dL, respectively. Hemoglobin and hematocrit were 8.9 ± 1.2 g/dL, and 28.8 ± 3.9%, respectively, whereas transferrin saturation and serum ferritin were 29.8 ± 11.0% and 100 (54-172) ng/mL, respectively. Serum ferritin significantly correlated in a positive manner with the total dose of iron orally administered during the previous 6 months (r = 0.185, P = .0013). HGS and muscle quality were 23.1 ± 10.4 kg and 11.6 ± 3.8 kg/kg, respectively. In multivariate analysis to elucidate the factors associated with HGS and muscle quality in 300 hemodialysis patients, which included transferrin saturation and log serum ferritin, in addition to age, gender, hemodialysis duration, the presence/absence of diabetes, body mass index as independent variables, log serum ferritin emerged as a significant and independent factor which associated in a negative fashion with HGS (β = -0.091, P = .0395) and tendency toward negative association with muscle quality (β = -0.100, P = .0754). In summary, the present study demonstrated the significant association of serum ferritin with HGS and muscle quality in hemodialysis patients and thus suggested that we should be careful of iron overload to avoid its possible harmful effect on muscle in such patients. Copyright © 2016 National Kidney

Functionalization and Characterization of Magnetic Nanoparticles for the Detection of Ferritin Accumulation in Alzheimer's Disease.

PubMed

Fernández, Tamara; Martínez-Serrano, Alberto; Cussó, Lorena; Desco, Manuel; Ramos-Gómez, Milagros

2018-05-16

Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the presence of some of the pathological signs of AD. In the present study, we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an antiferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations. Both in vitro and after intravenous injection, functionalized magnetic nanoparticles were able to recognize and bind specifically to the ferritin protein accumulated in the subiculum area of the AD transgenic mice.

Effect of the structure of gallic acid and its derivatives on their interaction with plant ferritin.

PubMed

Wang, Qunqun; Zhou, Kai; Ning, Yong; Zhao, Guanghua

2016-12-15

Gallic acid and its derivatives co-exist with protein components in foodstuffs, but there is few report on their interaction with proteins. On the other hand, plant ferritin represents not only a novel class of iron supplement, but also a new nanocarrier for encapsulation of bioactive nutrients. However, plant ferritin is easy to be degraded by pepsin in the stomach, thereby limiting its application. Herein, we investigated the interaction of gallic acid and its derivatives with recombinant soybean seed H-2 ferritin (rH-2). We found that these phenolic acids interacted with rH-2 in a structure-dependent manner; namely, gallic acid (GA), methyl gallate (MEGA) and propyl gallate (PG) having three HO groups can bind to rH-2, while their analogues with two HO groups cannot. Consequently, such binding largely inhibited ferritin degradation by pepsin. These findings advance our understanding of the relationship between the structure and function of phenolic acids. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elevated CO2 enhances biological contributions to elevation change in coastal wetlands by offsetting stressors associated with sea-level rise

USGS Publications Warehouse

Cherry, J.A.; McKee, K.L.; Grace, J.B.

2009-01-01

1. Sea-level rise, one indirect consequence of increasing atmospheric CO2, poses a major challenge to long-term stability of coastal wetlands. An important question is whether direct effects of elevated CO 2 on the capacity of marsh plants to accrete organic material and to maintain surface elevations outweigh indirect negative effects of stressors associated with sea-level rise (salinity and flooding). 2. In this study, we used a mesocosm approach to examine potential direct and indirect effects of atmospheric CO2 concentration, salinity and flooding on elevation change in a brackish marsh community dominated by a C3 species, Schoenoplectus americanus, and a C4 grass, Spartina patens. This experimental design permitted identification of mechanisms and their role in controlling elevation change, and the development of models that can be tested in the field. 3. To test hypotheses related to CO2 and sea-level rise, we used conventional anova procedures in conjunction with structural equation modelling (SEM). SEM explained 78% of the variability in elevation change and showed the direct, positive effect of S. americanus production on elevation. The SEM indicated that C3 plant response was influenced by interactive effects between CO2 and salinity on plant growth, not a direct CO2 fertilization effect. Elevated CO2 ameliorated negative effects of salinity on S. americanus and enhanced biomass contribution to elevation. 4. The positive relationship between S. americanus production and elevation change can be explained by shoot-base expansion under elevated CO 2 conditions, which led to vertical soil displacement. While the response of this species may differ under other environmental conditions, shoot-base expansion and the general contribution of C3 plant production to elevation change may be an important mechanism contributing to soil expansion and elevation gain in other coastal wetlands. 5. Synthesis. Our results revealed previously unrecognized interactions and

Sea level and turbidity controls on mangrove soil surface elevation change

USGS Publications Warehouse

Lovelock, Catherine E.; Fernanda Adame, Maria; Bennion, Vicki; Hayes, Matthew; Reef, Ruth; Santini, Nadia; Cahoon, Donald R.

2015-01-01

Increases in sea level are a threat to seaward fringing mangrove forests if levels of inundation exceed the physiological tolerance of the trees; however, tidal wetlands can keep pace with sea level rise if soil surface elevations can increase at the same pace as sea level rise. Sediment accretion on the soil surface and belowground production of roots are proposed to increase with increasing sea level, enabling intertidal habitats to maintain their position relative to mean sea level, but there are few tests of these predictions in mangrove forests. Here we used variation in sea level and the availability of sediments caused by seasonal and inter-annual variation in the intensity of La Nina-El Nino to assess the effects of increasing sea level on surface elevation gains and contributing processes (accretion on the surface, subsidence and root growth) in mangrove forests. We found that soil surface elevation increased with mean sea level (which varied over 250 mm during the study) and with turbidity at sites where fine sediment in the water column is abundant. In contrast, where sediments were sandy, rates of surface elevation gain were high, but not significantly related to variation in turbidity, and were likely to be influenced by other factors that deliver sand to the mangrove forest. Root growth was not linked to soil surface elevation gains, although it was associated with reduced shallow subsidence, and therefore may contribute to the capacity of mangroves to keep pace with sea level rise. Our results indicate both surface (sedimentation) and subsurface (root growth) processes can influence mangrove capacity to keep pace with sea level rise within the same geographic location, and that current models of tidal marsh responses to sea level rise capture the major feature of the response of mangroves where fine, but not coarse, sediments are abundant.

Creation of energetic biothermite inks using ferritin liquid protein

PubMed Central

Slocik, Joseph M.; McKenzie, Ruel; Dennis, Patrick B.; Naik, Rajesh R.

2017-01-01

Energetic liquids function mainly as fuels due to low energy densities and slow combustion kinetics. Consequently, these properties can be significantly increased through the addition of metal nanomaterials such as aluminium. Unfortunately, nanoparticle additives are restricted to low mass fractions in liquids because of increased viscosities and severe particle agglomeration. Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to overcoming low mass fractions of nanoparticles, producing stable nanoparticle dispersions and simultaneously offering a source of oxidizing agents for combustion of reactive nanomaterials. Here, we use iron oxide-loaded ferritin proteins to create a stable and highly energetic liquid composed of aluminium nanoparticles and ferritin proteins for printing and forming 3D shapes and structures. In total, this bioenergetic liquid exhibits increased energy output and performance, enhanced dispersion and oxidation stability, lower activation temperatures, and greater processability and functionality. PMID:28447665

Cerebrospinal fluid ferritin and albumin index: potential candidates for scoring system to differentiate between bacterial and viral meningitis in children.

PubMed

Jebamalar, Angelin A; Prabhat; Balakrishnapillai, Agiesh K; Parmeswaran, Narayanan; Dhiman, Pooja; Rajendiran, Soundravally

2016-07-01

To evaluate the diagnostic role of cerebrospinal fluid (CSF) ferritin and albumin index (AI = CSF albumin/serum albumin × 1000) in differentiating acute bacterial meningitis (ABM) from acute viral meningitis (AVM) in children. The study included 42 cases each of ABM and AVM in pediatric age group. Receiver operating characteristic (ROC) analysis was carried out for CSF ferritin and AI. Binary logistic regression was also done. CSF ferritin and AI were found significantly higher in ABM compared to AVM. Model obtained using AI and CSF ferritin along with conventional criteria is better than existing models.

7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. ENTRANCE VIEW OF ELEVATOR SHAFT AT GROUND LEVEL. VIEW SHOWS VERTICAL LADDER AND CAGE ALONG ELEVATOR SHAFT. - U.S. Naval Base, Pearl Harbor, Signal Tower, Corner of Seventh Street & Avenue D east of Drydock No. 1, Pearl City, Honolulu County, HI

Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

PubMed

DeVita, M V; Frumkin, D; Mittal, S; Kamran, A; Fishbane, S; Michelis, M F

2003-11-01

Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33% were enrolled. Subjects were divided as follows: Group 1: target SFer of 200 ng/ml, Group 2: target SFer of 400 ng/ml. Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target. HCT was maintained between 32.5% and 36% by adjusting rHuEPO dosage. Mean SFer concentration at the study conclusion in Group 1: 261 ng/ml; Group 2: 387 ng/ml. The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week (250 - 219 U/kg bw/wk) while in Group 2 it was 154 U/kg body weight/week (312 - 158 U/kg bw/wk) (p < 0.001). There was no difference in HCT between groups. Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements.

Plasma Levels of Aminothiols, Nitrite, Nitrate, and Malondialdehyde in Myelodysplastic Syndromes in the Context of Clinical Outcomes and as a Consequence of Iron Overload

PubMed Central

Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

2014-01-01

The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001) , homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease. PMID:24669287

Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in myelodysplastic syndromes in the context of clinical outcomes and as a consequence of iron overload.

PubMed

Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

2014-01-01

The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001), homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease.

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias

PubMed Central

Porter, John B; Lin, Kai-Hsin; Beris, Photis; Forni, Gian Luca; Taher, Ali; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Thein, Swee Lay

2011-01-01

Objectives It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. Methods The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10–30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Results Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (−26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (<0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). Conclusions At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism. PMID:21649735

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias.

PubMed

Porter, John B; Lin, Kai-Hsin; Beris, Photis; Forni, Gian Luca; Taher, Ali; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Thein, Swee Lay

2011-10-01

It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10-30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (-26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (< 0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism. © 2011 John Wiley & Sons A/S.

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes.

PubMed

Artz, Andrew S; Logan, Brent; Zhu, Xiaochun; Akpek, Gorgun; Bufarull, Rodrigo Martino; Gupta, Vikas; Lazarus, Hillard M; Litzow, Mark; Loren, Alison; Majhail, Navneet S; Maziarz, Richard T; McCarthy, Philip; Popat, Uday; Saber, Wael; Spellman, Stephen; Ringden, Olle; Wickrema, Amittha; Pasquini, Marcelo C; Cooke, Kenneth R

2016-11-01

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. Copyright© Ferrata Storti Foundation.

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes

PubMed Central

Artz, Andrew S.; Logan, Brent; Zhu, Xiaochun; Akpek, Gorgun; Bufarull, Rodrigo Martino; Gupta, Vikas; Lazarus, Hillard M.; Litzow, Mark; Loren, Alison; Majhail, Navneet S.; Maziarz, Richard T.; McCarthy, Philip; Popat, Uday; Saber, Wael; Spellman, Stephen; Ringden, Olle; Wickrema, Amittha; Pasquini, Marcelo C.; Cooke, Kenneth R.

2016-01-01

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. PMID:27662010

Plants with elevated levels of glucan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pauly, Markus; Kraemer, Florian J.; Hake, Sarah

The present disclosure relates to mutations in licheninase genes encoding polypeptides with decreased licheninase activity, which when expressed in plants results in elevated levels of glucan in the plants. In particular, the disclosure relates to licheninase nucleic acids and polypeptides related to glucan accumulation in plants, plants with reduced expression of a licheninase nucleic acid, and methods related to the generation of plants with increased glucan content in the cell walls of leaf tissue.

Ferritin Decorated PLGA/Paclitaxel Loaded Nanoparticles Endowed with an Enhanced Toxicity Toward MCF-7 Breast Tumor Cells.

PubMed

Turino, Ludmila N; Ruggiero, Maria R; Stefanìa, Rachele; Cutrin, Juan C; Aime, Silvio; Geninatti Crich, Simonetta

2017-04-19

Polylactic and glycolic acid nanoparticles (PLGA-NPs), coated with L-ferritin, are exploited for the simultaneous delivery of paclitaxel and an amphiphilic Gd based MRI contrast agent into breast cancer cells (MCF7). L-ferritin has been covalently conjugated to the external surface of PLGA-NPs exploiting NHS activated carboxylic groups. The results confirmed that nanoparticles decorated with L-ferritin have many advantages with respect to both albumin-decorated and nondecorated particles. Ferritin moieties endow PLGA-NPs with targeting capability, exploiting SCARA5 receptors overexpressed by these tumor cells, that results in an increased paclitaxel cytotoxicity. Moreover, protein coating increased nanoparticle stability, thus reducing the fast and aspecific drug release before reaching the target. The theranostic potential of the nanoparticles has been demonstrated by evaluating the signal intensity enhancement on T 1 -weighted MRI images of labeled MCF7 cells. The results were compared with that obtained with MDA cells used as negative control due to their lower SCARA5 expression.

Heterogeneity in horse ferritins. A comparative study of surface charge, iron content and kinetics of iron uptake.

PubMed Central

Russell, S M; Harrison, P M

1978-01-01

Horse ferritins from different organs show heterogeneity on electrofocusing in Ampholine gradients. Both ferritin and apoferritin from liver and spleen could be fractionated with respect to surface charge by serial precipitation with (NH4)2SO4. In the ferritin fractions, increasing iron content parallels increasing isoelectric point. After removal of their iron, those fractions which originally contained most iron accumulated added iron at the fastest rates. When unfractionated ferritins from different organs were compared the average isoelectric point increased in order spleen less than liver less than kidney less than heart. The order of initial rates of iron uptake by the apoferritins was spleen greater than kidney greater than heart and initial average iron contents also followed this order. The relatively low rates of iron accumulation by iron-poor molecules may have been due to structural alteration, to degradation, to activation of the iron-rich molecules or to other factors. Images Fig. 1. Fig. 2. PMID:736908

The iron content and ferritin contribution in fresh, dried, and toasted nori, Pyropia yezoensis.

PubMed

Masuda, Taro; Yamamoto, Ami; Toyohara, Haruhiko

2015-01-01

Iron is one of the essential trace elements for humans. In this study, the iron contents in fresh, dried, and toasted nori (Pyropia yezoensis) were analyzed. The mean iron content of fresh, dried, and toasted nori were 19.0, 22.6, and 26.2 mg/100 g (dry weight), respectively. These values were superior to other food of plant origin. Furthermore, most of the iron in nori was maintained during processing, such as washing, drying, and toasting. Then, the form of iron in fresh, dried, and toasted nori was analyzed. As a result, an iron storage protein ferritin contributed to iron storage in raw and dried nori, although the precise rate of its contribution is yet to be determined, while ferritin protein cage was degraded in the toasted nori. It is the first report that verified the ferritin contribution to iron storage in such edible macroalgae with commercial importance.

Inter-subunit electrostatic interactions in ferritin molecule: comparison with inter-molecular interactions in crystals

NASA Astrophysics Data System (ADS)

Takahashi, Takuya; Hogyoku, Michiru; Nagayama, Kuniaki

1996-10-01

We evaluated the contribution of electrostatic interactions to the stability of macromolecular assembly in a horse L ferritin molecule composed of 24 subunits and the three-dimensional crystal of the ferritin molecules with numerical calculation of Poisson-Boltzmann equation based on dielectric model. The calculation showed that the electrostatic energy both favors the assembly of the 24 subunits and the crystalline assembly of the ferritin molecules (i.e., 24-mers). Short-range interactions less than 5 Å such as salt bridges and hydrogen bonds were important for both the subunit assembly and the crystalline assembly. To elucidate the strong stabilization by electrostatic interactions in both the ferritin 24-mer and its crystal, we analyzed the contribution of individual atoms. It revealed that the stabilization was arising from buried salt bridges or hydrogen bonds, which yielded more than 5 kcal/mol in some interactions. These large electrostatic stabilization and also the unexpected small ionic strength dependence was different from those of bovine pancreatic trypsin inhibitor (BPTI) orthorhombic and pig-insulin cubic crystals previously calculated. We also evaluated changes of the accessible surface area (ASA) and hydration free energy in accordance with the process of the subunit assembly. The change of hydration free energy, which was very large (i.e. ˜ + 100 kcal/mol/subunit) and unfavorable for the assembly, was proportional to the electrostatic hydration energy (i.e. Born energy change in hydration process). Hydrophobic groups were likely to appear more frequently than hydrophilic groups at the subunit interfaces. These results suggest that the molecular structure of the ferritin 24-mer and the crystal structure of the 24-mers were both stabilized by local electrostatic interactions, in particular. We view protein crystals as an extension of the protein oligomer to an infinite number of subunits association.

Sensitive detection of surface- and size-dependent direct and indirect band gap transitions in ferritin.

PubMed

Colton, J S; Erickson, S D; Smith, T J; Watt, R K

2014-04-04

Ferritin is a protein nano-cage that encapsulates minerals inside an 8 nm cavity. Previous band gap measurements on the native mineral, ferrihydrite, have reported gaps as low as 1.0 eV and as high as 2.5-3.5 eV. To resolve this discrepancy we have used optical absorption spectroscopy, a well-established technique for measuring both direct and indirect band gaps. Our studies included controls on the protein nano-cage, ferritin with the native ferrihydrite mineral, and ferritin with reconstituted ferrihydrite cores of different sizes. We report measurements of an indirect band gap for native ferritin of 2.140 ± 0.015 eV (579.7 nm), with a direct transition appearing at 3.053 ± 0.005 eV (406.1 nm). We also see evidence of a defect-related state having a binding energy of 0.220 ± 0.010 eV . Reconstituted ferrihydrite minerals of different sizes were also studied and showed band gap energies which increased with decreasing size due to quantum confinement effects. Molecules that interact with the surface of the mineral core also demonstrated a small influence following trends in ligand field theory, altering the native mineral's band gap up to 0.035 eV.

Atom Probe Tomographic Mapping Directly Reveals the Atomic Distribution of Phosphorus in Resin Embedded Ferritin

NASA Astrophysics Data System (ADS)

Perea, Daniel E.; Liu, Jia; Bartrand, Jonah; Dicken, Quinten; Thevuthasan, S. Theva; Browning, Nigel D.; Evans, James E.

2016-02-01

Here we report the atomic-scale analysis of biological interfaces within the ferritin protein using atom probe tomography that is facilitated by an advanced specimen preparation approach. Embedding ferritin in an organic polymer resin lacking nitrogen provided chemical contrast to visualise atomic distributions and distinguish the inorganic-organic interface of the ferrihydrite mineral core and protein shell, as well as the organic-organic interface between the ferritin protein shell and embedding resin. In addition, we definitively show the atomic-scale distribution of phosphorus as being at the surface of the ferrihydrite mineral with the distribution of sodium mapped within the protein shell environment with an enhanced distribution at the mineral/protein interface. The sample preparation method is robust and can be directly extended to further enhance the study of biological, organic and inorganic nanomaterials relevant to health, energy or the environment.

Atom Probe Tomographic Mapping Directly Reveals the Atomic Distribution of Phosphorus in Resin Embedded Ferritin

PubMed Central

Perea, Daniel E.; Liu, Jia; Bartrand, Jonah; Dicken, Quinten; Thevuthasan, S. Theva; Browning, Nigel D.; Evans, James E.

2016-01-01

Here we report the atomic-scale analysis of biological interfaces within the ferritin protein using atom probe tomography that is facilitated by an advanced specimen preparation approach. Embedding ferritin in an organic polymer resin lacking nitrogen provided chemical contrast to visualise atomic distributions and distinguish the inorganic-organic interface of the ferrihydrite mineral core and protein shell, as well as the organic-organic interface between the ferritin protein shell and embedding resin. In addition, we definitively show the atomic-scale distribution of phosphorus as being at the surface of the ferrihydrite mineral with the distribution of sodium mapped within the protein shell environment with an enhanced distribution at the mineral/protein interface. The sample preparation method is robust and can be directly extended to further enhance the study of biological, organic and inorganic nanomaterials relevant to health, energy or the environment. PMID:26924804

Iron-based ferritin nanocore as a contrast agent.

PubMed

Sana, Barindra; Johnson, Eric; Sheah, Kenneth; Poh, Chueh Loo; Lim, Sierin

2010-09-01

Self-assembling protein cages have been exploited as templates for nanoparticle synthesis. The ferritin molecule, a protein cage present in most living systems, stores excess soluble ferrous iron in the form of an insoluble ferric complex within its cavity. Magnetic nanocores formed by loading excess iron within an engineered ferritin from Archaeoglobus fulgidus (AfFtn-AA) were studied as a potential magnetic resonance (MR) imaging contrast agent. The self-assembly characteristics of the AfFtn-AA were investigated using dynamic light scattering technique and size exclusion chromatography. Homogeneous size distribution of the assembled nanoparticles was observed using transmission electron microscopy. The magnetic properties of iron-loaded AfFtn-AA were studied using vibrating sample magnetometry. Images obtained from a 3.0 T whole-body MRI scanner showed significant brightening of T(1) images and signal loss of T(2) images with increased concentrations of iron-loaded AfFtn-AA. The analysis of the MR image intensities showed extremely high R(2) values (5300 mM(-1) s(-1)) for the iron-loaded AfFtn-AA confirming its potential as a T(2) contrast agent.

Ferritin protein nanocages use ion channels, catalytic sites, and nucleation channels to manage iron/oxygen chemistry.

PubMed

Theil, Elizabeth C

2011-04-01

The ferritin superfamily is composed of ancient, nanocage proteins with an internal cavity, 60% of total volume, that reversibly synthesize solid minerals of hydrated ferric oxide; the minerals are iron concentrates for cell nutrition as well as antioxidants due to ferrous and oxygen consumption during mineralization. The cages have multiple iron entry/exit channels, oxidoreductase enzyme sites, and, in eukaryotes, Fe(III)O nucleation channels with clustered exits that extend protein activity to include facilitated mineral growth. Ferritin protein cage differences include size, amino acid sequence, and location of the active sites, oxidant substrate and crystallinity of the iron mineral. Genetic regulation depends on iron and oxygen signals, which in animals includes direct ferrous signaling to RNA to release and to ubiquitin-ligases to degrade the protein repressors. Ferritin biosynthesis forms, with DNA, mRNA and the protein product, a feedback loop where the genetic signals are also protein substrates. The ferritin protein nanocages, which are required for normal iron homeostasis and are finding current use in the delivery of nanodrugs, novel nanomaterials, and nanocatalysts, are likely contributors to survival and success during the transition from anaerobic to aerobic life. Copyright © 2011. Published by Elsevier Ltd.

Ferritin Protein Nanocages Use Ion Channels, Catalytic Sites, and Nucleation Channels To Manage Iron/Oxygen Chemistry

PubMed Central

Theil, Elizabeth C.

2011-01-01

The ferritin superfamily is composed of ancient, nanocage proteins with an internal cavity, 60% of total volume, that reversibly synthesize solid minerals of hydrated ferric oxide; the minerals are iron concentrates for cell nutrition as well as antioxidants due to ferrous and oxygen consumption during mineralization. The cages have multiple iron entry/exit channels, oxidoreductase enzyme sites, and, in eukaryotes, Fe(III)O nucleation channels with clustered exits that extend protein activity to include facilitated mineral growth. Ferritin protein cage differences include size, amino acid sequence, and location of the active sites, oxidant substrate and crystallinity of the iron mineral. Genetic regulation depends on iron and oxygen signals, which in animals includes direct ferrous signaling to RNA to release and to ubiquitin-ligases to degrade the protein repressors. Ferritin biosynthesis forms, with DNA, mRNA and the protein product, a feedback loop where the genetic signals are also protein substrates. The ferritin protein nanocages, which are required for normal iron homeostasis and are finding current use in delivery of nanodrugs, novel nanomaterials, and nanocatalysts, are likely contributors to survival and success during the transition from anaerobic to aerobic life. PMID:21296609

Characteristics of structure, composition, mass spectra, and iron release from the ferritin of shark liver (Sphyrna zygaena).

PubMed

Huang, He-Qing; Xiao, Zhi-Qun; Chen, Xu; Lin, Qing-Mei; Cai, Zong-Wei; Chen, Ping

2004-11-01

The ferritin consists of a protein shell constructed of 24 subunits and an iron core. The liver ferritin of Sphyrna zygaena (SZLF) purified by column chromatography is a protein composed of eight ferritins containing varying iron numbers ranging from 400+/-20 Fe3+/SZLF to 1890+/-20 Fe3+/SZLF within the protein shell. Nature SZLF (SZLFN) consisting of holoSZLF and SZLF with unsaturated iron (SZLFUI) to have been purified with polyacrylamide gel electrophoresis (PAGE) exhibited five ferritin bands with different pI values ranging from 4.0 to 7.0 in the gel slab of isoelectric focusing (IEF). HoloSZLF purified by PAGE (SZLFE) not only had 1890+/-20 Fe3+/SZLFE but also showed an identical size of iron core observed by transmission electron microscopy (TEM). Molecular weight of approximately 21 kDa for SZLFE subunit was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Four peaks of molecular ions at mass/charge (m/z) ratios of 10611.07, 21066.52, 41993.16, and 63555.64 that come from the SZLFE were determined by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS), which were identified as molecular ions of the ferritin subunit (M+) and its polymers, namely, [M]2+, [M]+, [2M]+, and [3M]+, respectively. Both SZLFE and a crude extract from shark liver of S. zygaena showed similar kinetic characteristics of complete iron release with biphasic behavior. In addition, a combined technique of visible spectrometry and column chromatography was used for studying ratio of phosphate to Fe3+ within the SZLFE core. Interestingly, this ratio maintained invariable even after the iron release, which differed from that of other mammal ferritins.

High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates

PubMed Central

Zahrieh, David; Young, Sean G.; Oleson, Jacob; Ryckman, Kelli K.; Wels, Brian; Simmons, Donald L.; Saftlas, Audrey

2017-01-01

Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1–3 days of birth among Iowa newborns, linked with the area of mother’s residence at the time of birth, we examine the spatial patterns of elevated (>5 μg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 μg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 μg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact. PMID:28520816

Size-dependent structural evolution of the biomineralized iron-core nanoparticles in ferritins

NASA Astrophysics Data System (ADS)

Lee, Eunsook; Kim, D. H.; Hwang, Jihoon; Lee, Kiho; Yoon, Sungwon; Suh, B. J.; Hyun Kim, Kyung; Kim, J.-Y.; Jang, Z. H.; Kim, Bongjae; Min, B. I.; Kang, J.-S.

2013-04-01

The structural identity of the biomineralized iron core nanoparticles in Helicobacter pylori ferritins (Hpf's) has been determined by employing soft x-ray absorption spectroscopy and soft x-ray magnetic circular dichroism. Valence states of Fe ions are nearly trivalent in all Hpf's, indicating that the amount of magnetite (Fe3O4) is negligible. With increasing filling of Fe ions, the local configurations of Fe3+ ions change from the mixture of the tetrahedral and octahedral symmetries to the octahedral symmetry. These results demonstrate that the biomineralization of the ferritin core changes from maghemite-like (γ-Fe2O3) formation to hematite-like (α-Fe2O3) formation with increasing Fe content.

Enhanced iron and zinc accumulation in genetically engineered pineapple plants using soybean ferritin gene.

PubMed

Mhatre, Minal; Srinivas, Lingam; Ganapathi, Thumballi R

2011-12-01

Pineapple (Ananas comosus L. Merr., cv. "Queen") leaf bases were transformed with Agrobacterium tumefaciens strain EHA 105 harboring the pSF and pEFESF plasmids with soybean ferritin cDNA. Four to eight percent of the co-cultivated leaf bases produced multiple shoots 6 weeks after transfer to Murashige and Skoog's medium supplemented with α-naphthalene acetic acid 1.8 mg/l, indole-3-butyric acid 2.0 mg/l, kinetin 2.0 mg/l, cefotaxime 400 mg/l, and kanamycin 50 mg/l. Putatively transformed shoots (1-2 cm) were selected and multiplied on medium of the same composition and elongated shoots (5 cm) were rooted on liquid rooting medium supplemented with cefotaxime 400 mg/l and kanamycin 100 mg/l. The rooted plants were analyzed through PCR, genomic Southern analysis, and reverse transcription PCR. The results clearly confirmed the integration and expression of soybean ferritin gene in the transformed plants. Atomic absorption spectroscopic analysis carried out with six independently transformed lines of pSF and pEFE-SF revealed a maximum of 5.03-fold increase in iron and 2.44-fold increase in zinc accumulation in the leaves of pSF-transformed plants. In pEFE-SF-transformed plants, a 3.65-fold increase in iron and 2.05-fold increase in zinc levels was observed. Few of the transgenic plants were hardened in the greenhouse and are being grown to maturity to determine the enhanced iron and zinc accumulation in the fruits. To the best of our knowledge this is the first report on the transformation of pineapple with soybean ferritin for enhanced accumulation of iron and zinc content in the transgenic plants.

A Mutation Directs the Structural Switch of DNA Binding Proteins under Starvation to a Ferritin-like Protein Cage.

PubMed

Williams, Sunanda Margrett; Chandran, Anu Vijayakumari; Prakash, Sunita; Vijayan, Mamannamana; Chatterji, Dipankar

2017-09-05

Proteins of the ferritin family are ubiquitous in living organisms. With their spherical cage-like structures they are the iron storehouses in cells. Subfamilies of ferritins include 24-meric ferritins and bacterioferritins (maxiferritins), and 12-meric Dps (miniferritins). Dps safeguards DNA by direct binding, affording physical protection and safeguards from free radical-mediated damage by sequestering iron in its core. The maxiferritins can oxidize and store iron but cannot bind DNA. Here we show that a mutation at a critical interface in Dps alters its assembly from the canonical 12-mer to a ferritin-like 24-mer under crystallization. This structural switch was attributed to the conformational alteration of a highly conserved helical loop and rearrangement of the C-terminus. Our results demonstrate a novel concept of mutational switch between related protein subfamilies and corroborate the popular model for evolution by which subtle substitutions in an amino acid sequence lead to diversification among proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

mRNA Regulation of Cardiac Iron Transporters and Ferritin Subunits in a Mouse Model of Iron Overload

PubMed Central

Brewer, Casey J.; Wood, Ruth I.; Wood, John C.

2014-01-01

Iron cardiomyopathy is the leading cause of death in iron overload. Men have twice the mortality rate of women, though the cause is unknown. In hemojuvelin-knockout mice, a model of the disease, males load more cardiac iron than females. We postulated that sex differences in cardiac iron import cause differences in cardiac iron concentration. RT-PCR was used to measure mRNA of cardiac iron transporters in hemojuvelin-knockout mice. No sex differences were discovered among putative importers of non-transferrin bound iron (L-type and T-type calcium channels, ZRT/IRT-like protein 14 zinc channels). Transferrin-bound iron transporters were also analyzed; these are controlled by the iron regulatory element/iron regulatory protein (IRE/IRP) system. There was a positive relationship between cardiac iron and ferroportin mRNA in both sexes, but it was significantly steeper in females (p<0.05). Transferrin receptor 1 and divalent metal transporter 1 were more highly expressed in females than males (p<0.01 and p<0.0001, respectively), consistent with their lower cardiac iron levels, as predicted by IRE/IRP regulatory pathways. Light-chain (L) ferritin showed a positive correlation with cardiac iron that was nearly identical in males and females (R2=0.41, p<0.01 and R2=0.56, p<0.05, respectively), while heavy-chain (H) ferritin was constitutively expressed in both sexes. This represents the first report of IRE/IRP regulatory pathways in the heart. Transcriptional regulation of ferroportin was suggested in both sexes, creating a potential mechanism for differential set points for iron export. Constitutive H-ferritin expression suggests a logical limit to cardiac iron buffering capacity at levels known to produce heart failure in humans. PMID:25220979

4th level of 1913 elevator indicating sacking scale, part of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4th level of 1913 elevator indicating sacking scale, part of the bagging system and nate to the sewing machine. Discharge spout for the grain bin to the left - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

Urea-Driven Epigallocatechin Gallate (EGCG) Permeation into the Ferritin Cage, an Innovative Method for Fabrication of Protein-Polyphenol Co-assemblies.

PubMed

Yang, Rui; Liu, Yuqian; Meng, Demei; Chen, Zhiyu; Blanchard, Christopher L; Zhou, Zhongkai

2017-02-22

The 8 nm diameter cavity endows the ferritin cage with a natural space to encapsulate food components. In this work, urea was explored as a novel medium to facilitate the formation of ferritin-polyphenol co-assemblies. Results indicated that urea (20 mM) could expand the 4-fold channel size of apo-red bean ferritin (apoRBF) with an increased initial iron release rate υ 0 (0.22 ± 0.02 μM min -1 ) and decreased α-helix content (5.6%). Moreover, urea (20 mM) could facilitate the permeation of EGCG into the apoRBF without destroying the ferritin structure and thus form ferritin-EGCG co-assemblies (FECs) with an encapsulation ratio and loading capacity of 17.6 and 2.1% (w/w), respectively. TEM exhibited that FECs maintained a spherical morphology with a 12 nm diameter in size. Fluorescence analysis showed that urea intervention could improve the binding constant K [(1.22 ± 0.8) × 10 4 M -1 ] of EGCG to apoRBF. Furthermore, the EGCG thermal stability was significantly improved (20-60 °C) compared with free EGCG. Additionally, this urea-involved method was applicable for chlorogenic acid and anthocyanin encapsulation by the apoRBF cage. Thus, urea shows potential as a novel potential medium to encapsulate and stabilize bioactive polyphenols for food usage based on the ferritin protein cage structure.

Uric Acid Level and Elevated Blood Pressure in U.S. Adolescents

PubMed Central

Loeffler, Lauren F.; Navas-Acien, Ana; Brady, Tammy M.; Miller, Edgar R.; Fadrowski, Jeffrey J.

2012-01-01

Uric acid is associated with cardiovascular disease (CVD) and CVD risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of U.S. adolescents, a population with a relatively low prevalence of CVD and CVD risk factors. Among 6,036 adolescents 12-17 years of age examined in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) the mean age was 14.5 years, 17% were obese (body mass index [BMI] ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity and BMI percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex and height, for each 0.1 mg/dL increase in uric acid level was 1.38 (95% confidence interval [CI], 1.16 to 1.65). Compared to <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI, 1.38 to 3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy U.S. adolescents. Additional prospective studies and clinical trials are needed to determine if uric acid is merely a marker in a complex metabolic pathway, or causal of hypertension and thus a potential screening and therapeutic target. PMID:22353609

Evidence that ferritin is associated with light production in the mucus of the marine worm Chaetopterus

PubMed Central

Rawat, Renu; Deheyn, Dimitri D.

2016-01-01

The blue glow of the mucus from Chaetopterus involves a photoprotein, iron and flavins. Identity and respective role of these components remain, however, largely unresolved today, likely because of viscosity issues and inhibition of this system by oxidizers conventionally used to track bioluminescence activity. Here, we used gentle centrifugation to obtain a mucus supernatant showing no inhibition to oxidizers, allowing for further analysis. We applied conventional chromatographic techniques to isolate major proteins associated with light emission. Luminescence ability of elutriate fractions was tested with hydrogen peroxide to track photoprotein and/or protein-bound chromophore. Fractions producing light contained few major proteins, one with similarity to ferritin. Addition to the mucus of elements with inhibitory/potentiary effect on ferritin ferroxidase activity induced corresponding changes in light production, emphasizing the possible role of ferritin in the worm bioluminescence. DNA of the protein was cloned, sequenced, and expressed, confirming its identity to a Chaetopterus Ferritin (ChF). Both ferric and ferrous iron were found in the mucus, indicating the occurrence of both oxidase and reductase activity. Biochemical analysis showed ChF has strong ferroxidase activity, which could be a source of biological iron and catalytic energy for the worm bioluminescence when coupled to a reduction process with flavins. PMID:27830745

Association of Colecalciferol, Ferritin, and Anemia among Pregnant Women: Result from Cohort Study on Vitamin D Status and Its Impact during Pregnancy and Childhood in Indonesia

PubMed Central

Gumilang, Lani; Irianti, Setyorini; Wirhana, Deni; Permana, Irman; Sofjan, Liza; Duhita, Hesty; Tambunan, Lies Ani; Gurnadi, Jeffry Iman; Seno, Umar; Ghrahani, Reni; Indrati, Agnes Rengga; Sribudiani, Yunia; Yuniati, Tetty; Setiabudiawan, Budi

2018-01-01

Studies had shown that iron-cycling was disturbed by inflammatory process through the role of hepcidin. Pregnancy is characterized by shifts of interleukin. Our objective was to determine if 25(OH) vitamin D (colecalciferol) status was associated with ferritin, anemia, and its changes during pregnancy. Method. A cohort study was done in 4 cities in West Java, Indonesia, beginning in July 2016. Subjects were followed up until third trimester. Examinations included were maternal ferritin, colecalciferol, and haemoglobin level. Result. 191 (95.5%) subjects had low colecalciferol, and 151 (75.5%) among them were at deficient state. Anemia is found in 15 (7.5%) subjects, much lower than previous report. Proportion of anemia increased by trimester among women with colecalciferol deficiency. Ferritin status and prepregnancy body mass index in the first trimester were correlated with anemia (r = 0.147, p = 0.038 and r = −0.56, p = 0.03). Anemia in the second trimester was strongly correlated with anemia in the third trimester (r = 0.676, p < 0.01). Conclusion. Our study showed that the state of colecalciferol was not associated with either ferritin state or anemia, but proportion of anemia tends to increase by trimester in the colecalciferol deficient subjects. PMID:29888000

Treating elevated cholesterol levels: the great Satan in perspective.

PubMed

Gibaldi, M; Kradjan, W

1996-03-01

The purpose of this review is to provide perspective on the developments leading to the recognition of high cholesterol levels as a risk factor for coronary heart disease (CHD). Another objective is to consider the unfolding controversies regarding the relative value of cholesterol-lowering drug therapy in primary and secondary prevention. Should physicians use lipid-lowering drugs to treat patients with elevated cholesterol levels but no clinical evidence of coronary disease, or limit intervention to patients with a previous history of angina, coronary angioplasty, coronary artery bypass surgery, or myocardial infarction? This review finds inadequate data to support a recommendation for screening large populations for the presence of elevated cholesterol levels or for primary prevention in those known to have high cholesterol. On the other hand, there is mounting evidence to support vigorous intervention in those with known coronary disease. Further study is needed to determine whether a subset of patients with one or more well-defined risk factors would benefit from primary prevention.

Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral.

PubMed

Liu, Xiaofeng S; Patterson, Leslie D; Miller, Marvin J; Theil, Elizabeth C

2007-11-02

Pores regulate access between ferric-oxy biomineral inside and reductants/chelators outside the ferritin protein nanocage to control iron demineralization rates. The pore helix/loop/helix motifs that are contributed by three subunits unfold independently of the protein cage, as observed by crystallography, Fe removal rates, and CD spectroscopy. Pore unfolding is induced in wild type ferritin by increased temperature or urea (1-10 mM), a physiological urea range, 0.1 mM guanidine, or mutation of conserved pore amino acids. A peptide selected for ferritin pore binding from a combinatorial, heptapeptide library increased the rate of Fe demineralization 3-fold (p<0.001), similarly to a mutation that unfolded the pores. Conjugating the peptide to Desferal (desferrioxamine B mesylate), a chelator in therapeutic use, increased the rates to 8-fold (p<0.001). A second pore binding peptide had the opposite effect and decreased the rate of Fe demineralization 60% (p<0.001). The peptides could have pharmacological uses and may model regulators of ferritin demineralization rates in vivo or peptide regulators of gated pores in membranes. The results emphasize that small peptides can exploit the structural plasticity of protein pores to modulate function.

Magnetic properties of ferritin and akaganeite nanoparticles in aqueous suspension

NASA Astrophysics Data System (ADS)

Koralewski, Marceli; Pochylski, Mikołaj; Gierszewski, Jacek

2013-09-01

We have studied the magnetically induced optical birefringence Δ n of horse spleen ferritin (HSF) and aqueous suspensions of several different-sized iron oxyhydroxide nanoparticles coated with different polysaccharides mimicking ferritin. The structure and dimensions of the akaganeite mineral core were characterized by XRD and TEM, respectively. The stability of the suspensions in the measurement temperature range from 278 to 358 K was confirmed by UV-Vis absorption spectroscopy. The values of optical polarizability anisotropy Δ α, magnetic susceptibility anisotropy Δ χ, and permanent magnetic dipole moment μ m of the akaganeite nanoparticles have been estimated on the basis of the temperature dependence of the Cotton-Mouton (C-M) constant. The magnetic birefringence of Fe-sucrose has been described tentatively by different types of Langevin function allowing another estimation of Δ χ and μ m. The obtained permanent magnetic dipole moment μ m of the studied akaganeite nanoparticles proves small and comparable to that of HSF. The value of μ m is found to increase with decreasing nanoparticle diameter. Observed in a range spanning more than five orders of magnitude, the linear relation between the C-M constant and the iron concentration provides a basis for possible analytical application of the C-M effect in biomedicine. The established relation between the C-M constant and the nanoparticle diameter confirms that the dominant contribution to the measured magnetic birefringence comes from the magnetic susceptibility anisotropy Δ χ. A comparison of the C-M constants of the studied akaganeite nanoparticles with the data obtained for HSF provides evidence that the ferritin core behaves as a non-Euclidian solid.

Iron, Oxidative Stress, and Δ9 Stearoyl-CoenzymeA Desaturase Index (C16:1/C16:0): An Analysis Applying the National Health and Nutrition Examination Survey 2003–04

PubMed Central

Wu, Yue; Baylin, Ana; Colacino, Justin A

2018-01-01

Abstract Background Stearoyl-coenzyme A desaturase (SCD) is a key enzyme in fatty acid metabolism, and elevated SCD activity is associated with multiple adverse health outcomes. Diet, hormone levels, and environmental exposures are potential factors affecting SCD activity. Less is known about the relationship between micronutrients, including iron, and SCD activity. Objective The aim of this study was to investigate the association between serum ferritin level, a biomarker of circulating iron levels, and the Δ9 desaturase index (C16:1/C16:0), a biomarker of estimated SCD activity, among women in the United States. Methods The association between serum ferritin and the Δ9 desaturase index was assessed in a cross-sectional study of 447 female participants, aged 20–49 y, from NHANES 2003–2004. The multivariate analyses were performed utilizing generalized linear modeling, adjusting for potential confounders. Mediation of the relationship between serum ferritin and Δ9 desaturase index by γ-glutamyltranspeptidase (GGT), a biomarker of oxidative stress, was also assessed. Results Increased ferritin was significantly associated with a higher Δ9 desaturase index. Adjusting for waist circumference, age, race, and cotinine levels, an interquartile range increase in serum ferritin corresponded to 3.92% (95% CI: 0.88%, 7.05%) higher Δ9 desaturase index. GGT, the biomarker used to measure oxidative stress level, did not appear to mediate the association between ferritin and Δ9 desaturase index. After stratifying by pregnancy status, these associations were limited to nonpregnant individuals. Conclusions Elevated SCD activity may be associated with increased iron storage inside the human body; the association did not appear to be mediated via oxidative stress, as estimated by GGT levels.

Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population.

PubMed

Gan, Wei; Guan, Yu; Wu, Qian; An, Peng; Zhu, Jingwen; Lu, Ling; Jing, Li; Yu, Yu; Ruan, Sheng; Xie, Dong; Makrides, Maria; Gibson, Robert A; Anderson, Gregory J; Li, Huaixing; Lin, Xu; Wang, Fudi

2012-03-01

Transmembrane protease serine 6 (TMPRSS6) regulates iron homeostasis by inhibiting the expression of hepcidin. Multiple common variants in TMPRSS6 were significantly associated with serum iron in recent genome-wide association studies, but their effects in the Chinese remain to be elucidated. The objective was to determine whether the TMPRSS6 single nucleotide polymorphisms (SNPs) rs855791(V736A) and rs4820268(D521D) were associated with blood hemoglobin and plasma ferritin concentrations and risk of type 2 diabetes in Chinese individuals. The SNPs rs855791(V736A) and rs4820268(D521D) in the TMPRSS6 gene were genotyped and tested for their associations with plasma iron and type 2 diabetes risk in 1574 unrelated Chinese Hans from Beijing. The 2 TMPRSS6 SNPs rs855791(V736A) and rs4820268(D521D) were both significantly associated with plasma ferritin (P ≤ 0.0058), hemoglobin (P ≤ 0.0013), iron overload risk (P ≤ 0.0068), and type 2 diabetes risk (P ≤ 0.0314). None of the associations with hemoglobin or plasma ferritin remained significant (P ≥ 0.1229) when the 2 variants were both included in one linear regression model. A haplotype carrying both iron-lowering alleles from the 2 TMPRSS SNPs showed significant associations with lower hemoglobin (P = 0.0014), lower plasma ferritin (P = 0.0027), and a reduced risk of iron overload (P = 0.0017) and of type 2 diabetes (P = 0.0277). These findings suggest that TMPRSS6 variants were significantly associated with plasma ferritin, hemoglobin, risk of iron overload, and type 2 diabetes in Chinese Hans. The type 2 diabetes risk conferred by the TMPRSS6 SNPs is possibly mediated by plasma ferritin.

Correlation between liver iron concentration determined by magnetic resonance imaging and serum ferritin in adolescents with thalassaemia disease.

PubMed

Chuansumrit, Ampaiwan; Laothamathat, Jiraporn; Sirachainan, Nongnuch; Sungkarat, Witaya; Wongwerawattanakoon, Pakawan; Kumkrua, Patrapop

2016-08-01

MRI imaging is an alternative to serum ferritin for assessing iron overload in patients with thalassaemia disease. To correlate liver iron concentration (LIC) determined by MRI and clinical and biochemical parameters. An MRI study using cardiovascular magnetic resonance (CMR) tools to determine cardiac and liver iron was undertaken in adolescents with thalassaemia disease. Eighty-nine patients (48 males) with thalassaemia disease were enrolled. Seventy patients had been transfusion-dependent since a mean (SD) age of 3.8 (3.0) years, and 19 patients were not transfusiondependent. Mean (SD) haematocrit was 27.3 (2.9)%. Twenty-eight patients were splenectomized. Mean (SD) serum ferritin was 1673 (1506) μg/L. All transfusion-dependent patients received iron chelation at the mean (SD) age of 8.4 (3.5) years with either monotherapy of desferrioxamine, deferiprone, deferasirox or combined therapy of desferrioxamine and deferiprone, while only 5 of 19 patients who were not transfusion-dependent received oral chelation. The 89 patients underwent an MRI scan at the mean (SD) age of 14.8 (3.2) years. No patients had myocardial iron overload, but nine had severe liver iron overload, 27 had moderate liver iron overload, and 36 had mild liver iron overload. A significant correlation between liver T2* and serum ferritin was expressed as the equation: T2* (ms) = 28.080-7.629 log ferritin (μg/L) (r(2) 0.424, P = 0.0001). Patients with serum ferritin of >1000 to >2500 μg/L risked moderate and severe liver iron loading with the odds ratio ranging from 6.8 to 13.3 (95% CI 2.5-50.8). In thalassaemia, MRI is an alternative means of assessing iron stores, but when it is not available serum ferritin can be used to estimate liver T2*.

Ultrasensitive Nanoimmunosensor by coupling non-covalent functionalized graphene oxide platform and numerous ferritin labels on carbon nanotubes.

PubMed

Akter, Rashida; Jeong, Bongjin; Choi, Jong-Soon; Rahman, Md Aminur

2016-06-15

An ultrasensitive electrochemical nanostructured immunosensor for a breast cancer biomarker carbohydrate antigen 15-3 (CA 15-3) was fabricated using non-covalent functionalized graphene oxides (GO/Py-COOH) as sensor probe and multiwalled carbon nanotube (MWCNTs)-supported numerous ferritin as labels. The immunosensor was constructed by immobilizing a monoclonal anti-CA 15-3 antibody on the GO modified cysteamine (Cys) self-assembled monolayer (SAM) on an Au electrode (Au/Cys) through the amide bond formation between the carboxylic acid groups of GO/Py-COOH and amine groups of anti-CA 15-3. Secondary antibody conjugated MWCNT-supported ferritin labels (Ab2-MWCNT-Ferritin) were prepared through the amide bond formation between amine groups of Ab2 and ferritin and carboxylic acid groups of MWCNTs. The detection of CA 15-3 was based on the enhanced bioelectrocatalytic reduction of hydrogen peroxide mediated by hydroquinone (HQ) at the GO/Py-COOH-based sensor probe. The GO/Py-COOH-based sensor probe and Ab2-MWCNT-Ferritin labels were characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscope (SEM), transmission electron microscope (TEM), and x-ray photoelectron spectroscopy (XPS) techniques. Using differential pulse voltammetry (DPV) technique, CA 15-3 can be selectively detected as low as 0.01 ± 0.07 U/mL in human serum samples. Additionally, the proposed CA 15-3 immunosensor showed excellent selectivity and better stability in human serum samples, which demonstrated that the proposed immunosensor has potentials in proteomic researches and diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrical Conductivity of Ferritin Proteins by Conductive AFM

NASA Technical Reports Server (NTRS)

Xu, Degao; Watt, Gerald D.; Harb, John N.; Davis, Robert C.

2005-01-01

Electrical conductivity measurements were performed on single apoferritin and holoferritin molecules by conductive atomic force microscopy. Conductivity of self-assembled monolayer films of ferritin molecules on gold surfaces was also measured. Holoferritin was 5-25 times more conductive than apoferritin, indicating that for holoferritin most electron-transfer goes through the ferrihydrite core. With 1 V applied, the average electrical currents through single holoferritin and apoferritin molecules were 2.6 PA and 0.19 PA, respectively.

Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

NASA Technical Reports Server (NTRS)

Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

1997-01-01

We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

Non-native Co-, Mn-, and Ti-oxyhydroxide nanocrystals in ferritin for high efficiency solar energy conversion

NASA Astrophysics Data System (ADS)

Erickson, S. D.; Smith, T. J.; Moses, L. M.; Watt, R. K.; Colton, J. S.

2015-01-01

Quantum dot solar cells seek to surpass the solar energy conversion efficiencies achieved by bulk semiconductors. This new field requires a broad selection of materials to achieve its full potential. The 12 nm spherical protein ferritin can be used as a template for uniform and controlled nanocrystal growth, and to then house the nanocrystals for use in solar energy conversion. In this study, precise band gaps of titanium, cobalt, and manganese oxyhydroxide nanocrystals within ferritin were measured, and a change in band gap due to quantum confinement effects was observed. The range of band gaps obtainable from these three types of nanocrystals is 2.19-2.29 eV, 1.93-2.15 eV, and 1.60-1.65 eV respectively. From these measured band gaps, theoretical efficiency limits for a multi-junction solar cell using these ferritin-enclosed nanocrystals are calculated and found to be 38.0% for unconcentrated sunlight and 44.9% for maximally concentrated sunlight. If a ferritin-based nanocrystal with a band gap similar to silicon can be found (i.e. 1.12 eV), the theoretical efficiency limits are raised to 51.3% and 63.1%, respectively. For a current matched cell, these latter efficiencies become 41.6% (with an operating voltage of 5.49 V), and 50.0% (with an operating voltage of 6.59 V), for unconcentrated and maximally concentrated sunlight respectively.

Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

PubMed Central

Richardson, Jason R.; Roy, Ananya; Shalat, Stuart L.; von Stein, Richard T.; Hossain, Muhammad M.; Buckley, Brian; Gearing, Marla; Levey, Allan I.; German, Dwight C.

2014-01-01

IMPORTANCE The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). OBJECTIVE To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. DESIGN, SETTING, AND PARTICIPANTS A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. MAIN OUTCOMES AND MEASURES Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. RESULTS Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54–5.82; P < .001) and lower Mini-Mental State Examination scores (−1.605; range, −3.095 to −0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. CONCLUSIONS

Elevated serum pesticide levels and risk for Alzheimer disease.

PubMed

Richardson, Jason R; Roy, Ananya; Shalat, Stuart L; von Stein, Richard T; Hossain, Muhammad M; Buckley, Brian; Gearing, Marla; Levey, Allan I; German, Dwight C

2014-03-01

The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may

Elevated blood pressure, race/ethnicity, and C-reactive protein levels in children and adolescents.

PubMed

Lande, Marc B; Pearson, Thomas A; Vermilion, Roger P; Auinger, Peggy; Fernandez, Isabel D

2008-12-01

Adult hypertension is independently associated with elevated C-reactive protein levels, after controlling for obesity and other cardiovascular risk factors. The objective of this study was to determine, with a nationally representative sample of children, whether the relationship between elevated blood pressure and C-reactive protein levels may be evident before adulthood. Cross-sectional data for children 8 to 17 years of age who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 were analyzed. Bivariate analyses compared children with C-reactive protein levels of >3 mg/L versus elevated blood pressure and C-reactive protein levels. Among 6112 children, 3% had systolic blood pressure of >or=95th percentile and 1.3% had diastolic blood pressure of >or=95th percentile. Children with C-reactive protein levels of >3 mg/L had higher systolic blood pressure, compared with children with C-reactive protein levels of levels of <40 mg/dL, and Hispanic ethnicity were independent predictors of elevated C-reactive protein levels. Diastolic blood pressure did not differ between groups. Linear regression analyses showed that systolic blood pressure of >or=95th percentile was independently associated with C-reactive protein levels in boys but not girls. Subset analyses according to race/ethnicity demonstrated that the independent association of elevated systolic blood pressure with C-reactive protein levels was largely limited to black boys. These data indicate that there is interplay between race/ethnicity, elevated systolic blood pressure, obesity, and inflammation in children, a finding that has potential implications for disparities in cardiovascular disease later in life.

A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

PubMed Central

Liu, Chi-Ming; Tung, Tao-Hsin; Liu, Jorn-Hon; Chen, Victor Tze-Kai; Lin, Ching-Heng; Hsu, Chung-Te; Chou, Pesus

2005-01-01

AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study. PMID:15786537

Production and characterization of functional recombinant hybrid heteropolymers of camel hepcidin and human ferritin H and L chains.

PubMed

Boumaiza, Mohamed; Carmona, Fernando; Poli, Maura; Asperti, Michela; Gianoncelli, Alessandra; Bertuzzi, Michela; Ruzzenenti, Paola; Arosio, Paolo; Marzouki, Mohamed Nejib

2017-02-01

Hepcidin is a liver-synthesized hormone that plays a central role in the regulation of systemic iron homeostasis. To produce a new tool for its functional properties the cDNA coding for camel hepcidin-25 was cloned at the 5'end of human FTH sequence into the pASK-IBA43plus vector for expression in Escherichia coli The recombinant fusion hepcidin-ferritin-H subunit was isolated as an insoluble iron-containing protein. When alone it did not refold in a 24-mer ferritin molecule, but it did when renatured together with H- or L-ferritin chains. We obtained stable ferritin shells exposing about 4 hepcidin peptides per 24-mer shell. The molecules were then reduced and re-oxidized in a controlled manner to allow the formation of the proper hepcidin disulfide bridges. The functionality of the exposed hepcidin was confirmed by its ability to specifically bind the mouse macrophage cell line J774 that express ferroportin and to promote ferroportin degradation. This chimeric protein may be useful for studying the hepcidin-ferroportin interaction in cells and also as drug-delivery agent. © Crown copyright 2016.

Spectroscopic evidence for the role of a site of the di-iron catalytic center of ferritins in tuning the kinetics of Fe(ii) oxidation.

PubMed

Ebrahimi, Kourosh Honarmand; Bill, Eckhard; Hagedoorn, Peter-Leon; Hagen, Wilfred R

2016-11-15

Ferritin is a nanocage protein made of 24 subunits. Its major role is to manage intracellular concentrations of free Fe(ii) and Fe(iii) ions, which is pivotal for iron homeostasis across all domains of life. This function of the protein is regulated by a conserved di-iron catalytic center and has been the subject of extensive studies over the past 50 years. Yet, it has not been fully understood how Fe(ii) is oxidized in the di-iron catalytic center and it is not known why eukaryotic and microbial ferritins oxidize Fe(ii) with different kinetics. In an attempt to obtain a new insight into the mechanism of Fe(ii) oxidation and understand the origin of the observed differences in the catalysis of Fe(ii) oxidation among ferritins we studied and compared the mechanism of Fe(ii) oxidation in the eukaryotic human H-type ferritin (HuHF) and the archaeal ferritin from Pyrococcus furiosus (PfFtn). The results show that the spectroscopic characteristics of the intermediate of Fe(ii) oxidation and the Fe(iii)-products are the same in these two ferritins supporting the proposal of unity in the mechanism of Fe(ii) oxidation among eukaryotic and microbial ferritins. Moreover, we observed that a site in the di-iron catalytic center controls the distribution of Fe(ii) among subunits of HuHF and PfFtn differently. This observation explains the reported differences between HuHF and PfFtn in the kinetics of Fe(ii) oxidation and the amount of O 2 consumed per Fe(ii) oxidized. These results provide a fresh understanding of the mechanism of Fe(ii) oxidation by ferritins.

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women.

PubMed

Lao, Terence T; Tse, Ka-Yu; Chan, Louis Y; Tam, Kar-Fai; Ho, Lai-Fong

2003-11-01

To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.

Elevated voltage level I.sub.DDQ failure testing of integrated circuits

DOEpatents

Righter, Alan W.

1996-01-01

Burn in testing of static CMOS IC's is eliminated by I.sub.DDQ testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip.

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients

PubMed Central

Gaweda, Adam E; Bhat, Premila; Maglinte, Gregory A; Chang, Chun-Lan; Hill, Jerrold; Park, Grace S; Ashfaq, Akhtar; Gitlin, Matthew

2014-01-01

Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k − 2, k − 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k − 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k − 2, k − 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study. PMID:23968235

Elevated voltage level I{sub DDQ} failure testing of integrated circuits

DOEpatents

Righter, A.W.

1996-05-21

Burn in testing of static CMOS IC`s is eliminated by I{sub DDQ} testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip. 4 figs.

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

EPA Science Inventory

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Rece...

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVIE OXYGEN SPECIES

EPA Science Inventory

ARSENIC SPECIES. CAUSE RELEASE OF IRON , FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). R...

Heat aggregation studies of phycobilisomes, ferritin, insulin, and immunoglobulin by dynamic light scattering.

PubMed

Singh, B P; Bohidar, H B; Chopra, S

1991-10-15

Dynamic laser light scattering studies on the heat aggregation behavior of phycobilisomes (PBS), ferritin, insulin, and immunoglobulin (IgG) in dilute aqueous solutions has been reported. Except for PBS, results are reported for heat aggregation trends in these proteins for three different pH environments (4.0, 7.5, 9.1). For PBS, studies were performed only in the neutral buffer medium (pH 7.5). The experiments were performed in the very dilute concentration regime (between 0.23 and 1.8 gL-1). For all these samples heat aggregation and dissociation trends were found to be linear with temperature. Upon temperature reversal (self-cooling), hysteresis-like behavior observed in insulin was found to be predominantly large at pH 7.5. PBS, ferritin, and IgG showed no such behavior at any of three pH values, and retraced their path of aggregation while dissociating on temperature reversal. Heat aggregation and dissociation processes in ferritin were found to be independent of pH. The IgG samples showed smooth aggregation tendency only up to 35 degrees C in the buffer media pH 4.0 and 9.1, whereas for pH 7.0 the same could be observed until 60 degrees C. Low polydispersity in the correlation spectra was observed in case of all these samples.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

PubMed

Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

2008-08-01

It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Chemistry at the protein–mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster

PubMed Central

Pozzi, Cecilia; Di Pisa, Flavio; Mangani, Stefano; Turano, Paola

2017-01-01

X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (μ3-oxo)Tris[(μ2-peroxo)(μ2-glutamato-κO:κO′)](glutamato-κO)(diaquo)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin. PMID:28202724

Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster.

PubMed

Pozzi, Cecilia; Ciambellotti, Silvia; Bernacchioni, Caterina; Di Pisa, Flavio; Mangani, Stefano; Turano, Paola

2017-03-07

X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (μ 3 -oxo)Tris[(μ 2 -peroxo)(μ 2 -glutamato-κ O :κ O ')](glutamato-κ O )(diaquo)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin.

Iron-induced nitric oxide leads to an increase in the expression of ferritin during the senescence of Lotus japonicus nodules.

PubMed

Chungopast, Sirinapa; Duangkhet, Mallika; Tajima, Shigeyuki; Ma, Jian Feng; Nomura, Mika

2017-01-01

Iron is an essential nutrient for legume-rhizobium symbiosis and accumulates abundantly in the nodules. However, the concentration of free iron in the cells is strictly controlled to avoid toxicity. It is known that ferritin accumulates in the cells as an iron storage protein. During nodule senescence, the expression of the ferritin gene, Ljfer1, was induced in Lotus japonicus. We investigated a signal transduction pathway leading to the increase of Ljfer1 in the nodule. The Ljfer1 promoter of L. japonicus contains a conserved Iron-Dependent Regulatory Sequence (IDRS). The expression of Ljfer1 was induced by the application of iron or sodium nitroprusside, which is a nitric oxide (NO) donor. The application of iron to the nodule increased the level of NO. These data strongly suggest that iron-induced NO leads to increased expression of Ljfer1 during the senescence of L. japonicus nodules. Copyright © 2016 Elsevier GmbH. All rights reserved.

Epigallocatechin Gallate (EGCG) Decorating Soybean Seed Ferritin as a Rutin Nanocarrier with Prolonged Release Property in the Gastrointestinal Tract.

PubMed

Yang, Rui; Sun, Guoyu; Zhang, Min; Zhou, Zhongkai; Li, Quanhong; Strappe, Padraig; Blanchard, Chris

2016-09-01

The instability and low bioavailability of polyphenols limit their applications in food industries. In this study, epigallocatechin gallate (EGCG) and soybean seed ferritin deprived of iron (apoSSF) were fabricated as a combined double shell material to encapsulate rutin flavonoid molecules. Firstly, due to the reversible assembly characteristics of phytoferritin, rutin was successfully encapsulated within apoSSF to form a ferritin-rutin complex (FR) with an average molar ratio of 28.2: 1 (rutin/ferritin). The encapsulation efficiency and loading capacity of rutin were 18.80 and 2.98 %, respectively. EGCG was then bound to FR to form FR-EGCG composites (FRE), and the binding number of EGCG was 27.30 ± 0.68 with a binding constant K of (2.65 ± 0.11) × 10(4) M(-1). Furthermore, FRE exhibited improved rutin stability, and displayed prolonged release of rutin in simulated gastrointestinal tract fluid, which may be attributed to the external attachment of EGCG to the ferritin cage potentially reducing enzymolysis in GI fluid. In summary, this work demonstrates a novel nanocarrier for stabilization and sustained release of bioactive polyphenols.

A High Serum Iron Level Causes Mouse Retinal Iron Accumulation Despite an Intact Blood-Retinal Barrier

PubMed Central

Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L.

2015-01-01

The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms. PMID:25174877

Neighborhood Screening in Communities Throughout the Nation for Children with Elevated Blood Lead Levels

PubMed Central

Anderson, Dudley G.; Clark, John L.

1974-01-01

From the spring of 1971 to September 1973, neighborhood surveys were conducted in 58 communities throughout the nation to determine whether children with confirmed elevated blood lead levels could be identified. Another purpose of these screenings was to assist communities in identifying children with elevated blood lead levels and thereby demonstrate to community officials that such children do exist in communities screened. The children screened were not a random sample. In those communities where the initial elevated blood levels were confirmed all but seven had one or more children requiring followup and/or treatment. Of those children screened, black children had an elevated rate about three times as great as nonblack children. With few exceptions, the homes in the neighborhoods had at least one interior surface with sufficient quantities of lead paint to be dangerous if the paint were ingested. PMID:4831146

Study of the rhizobacterium Azospirillum brasilense Sp245 using Mössbauer spectroscopy with a high velocity resolution: Implication for the analysis of ferritin-like iron cores

NASA Astrophysics Data System (ADS)

Alenkina, I. V.; Oshtrakh, M. I.; Tugarova, A. V.; Biró, B.; Semionkin, V. A.; Kamnev, A. A.

2014-09-01

The results of a comparative study of two samples of the rhizobacterium Azospirillum brasilense (strain Sp245) prepared in different conditions and of human liver ferritin using Mössbauer spectroscopy with a high velocity resolution demonstrated the presence of ferritin-like iron (i.e. iron similar to that found in ferritin-like proteins) in the bacterium. Mössbauer spectra of these samples were fitted in two ways: as a rough approximation using a one quadrupole doublet fit (the homogeneous iron core model) and using a superposition of quadrupole doublets (the heterogeneous iron core model). Both results demonstrated differences in the Mössbauer parameters for mammalian ferritin and for bacterial ferritin-like iron. Moreover, some differences in the Mössbauer parameters were observed between the two samples of A. brasilense Sp245 related to the differences in their preparation conditions.

Cardiac hypertrophy elevates serum levels of fibroblast growth factor 23.

PubMed

Matsui, Isao; Oka, Tatsufumi; Kusunoki, Yasuo; Mori, Daisuke; Hashimoto, Nobuhiro; Matsumoto, Ayumi; Shimada, Karin; Yamaguchi, Satoshi; Kubota, Keiichi; Yonemoto, Sayoko; Higo, Tomoaki; Sakaguchi, Yusuke; Takabatake, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka

2018-05-08

Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals. Moreover, transverse aortic constriction also upregulated myocardial FGF23 expression in wild type mice. The promoter region of the FGF23 gene contains two putative nuclear factors of activated T cells (NFAT)-binding sites, with NFAT1 activating the promoter in a proximal NFAT-binding site dependent manner. Neither serum, urinary, or fractional excretion values of calcium and phosphate nor serum levels of 1,25(OH) 2 vitamin D were different between wild type and transgenic mice. Moreover, the renal expression of FGF receptors and α-Klotho was comparable. However, plasma levels of antidiuretic hormone were significantly increased in the transgenic mice, and aquaporin-2 immunohistochemical staining was mainly positive in the apical membrane of the collecting duct, compared to a primarily cytoplasmic staining in wild type mice. Real-time PCR analyses of kidney CYP27B1 and CYP24A1 expression in wild type mice showed that exogenous antidiuretic hormone blocked FGF23's actions on these vitamin D activating or inactivating enzymes. Finally, the renal resistance of transgenic mice to FGF23 was partly overcome by tolvaptan. Thus, LVH in transgenic mice is associated with an increase in myocardial and serum intact FGF23, with the kidneys being protected against FGF23 excess by elevated antidiuretic hormone levels. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Band gap variations in ferritin-templated nanocrystals

NASA Astrophysics Data System (ADS)

Colton, John; Erickson, Stephen; Smith, Trevor; Watt, Richard

2014-03-01

Ferritin is a 12 nm diameter protein shell with an 8 nm ``cage'' inside that can be used as a template for nanoparticle formation. The native particle is an iron oxide, ferrihydrite, but can be altered or replaced. We have used optical absorption spectroscopy to study the band gap of the ferrihydrite nanoparticles as they age (and become more crystalline), and as they respond to surface interactions with ions in solution. We will also present results of particle composition variations due to incorporation of oxo-anions into the interior of the nanoparticles and substitution of iron with other metals such as cobalt and manganese.

Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea.

PubMed

Kheirandish-Gozal, Leila; Sans Capdevila, Oscar; Kheirandish, Ebrahim; Gozal, David

2008-01-01

Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. Prospective study. Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF ELEVATOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF ELEVATOR SHOWING THE DOUBLED COLUMN FOR THE BUILDING EXPANSION JOINT AT COLUMN LINE AA-18. - Offutt Air Force Base, Glenn L. Martin-Nebraska Bomber Plant, Building D, Peacekeeper Drive, Bellevue, Sarpy County, NE

Elevated IL-8 levels during sickle cell crisis.

PubMed

Duits, A J; Schnog, J B; Lard, L R; Saleh, A W; Rojer, R A

1998-11-01

The vaso-occlusive process (VOC) in sickle cell disease is of a complex nature. It involves intricate interactions between sickle red blood cells, endothelium and probably also leukocytes. As these interactions are regulated by cytokines, we analyzed the role of the potent neutrophil chemokine IL-8 by measuring serum levels in sickle cell patients during sickle cell crisis. These results were compared to nonsymptomatics and healthy controls. In patients having a vaso-occlusive crisis both HbSS and HbSC patients showed significantly enhanced serum IL-8 levels compared to healthy controls. Several of these patients showed extremely elevated serum IL-8 levels which were independent of the crisis inducing factor. Furthermore, a sickle cell patient with VOC as a complication of rhGM-CSF treatment similarly showed high IL-8 serum levels at crisis onset. Nonsymptomatic sickle cell patients serum IL-8 levels were comparable to healthy controls. These results implicate a role for IL-8 at or during (the initiation of) sickle cell crisis.

Alteration of serum concentrations of manganese, iron, ferritin, and transferrin receptor following exposure to welding fumes among career welders.

PubMed

Lu, Ling; Zhang, Long-Lian; Li, G Jane; Guo, Wenrui; Liang, Wannian; Zheng, Wei

2005-03-01

This study was performed to determine airborne manganese levels during welding practice and to establish the relationship between long-term, low-level exposure to manganese and altered serum concentrations of manganese, iron, and proteins associated with iron metabolism in career welders. Ninety-seven welders (average age of 36 years) who have engaged in electric arc weld in a vehicle manufacturer were recruited as the exposed group. Welders worked 7-8h per day with employment duration of 1-33 years. Control subjects consisted of 91 employees (average age of 35 years) in the same factory but not in the welding profession. Ambient manganese levels in welders' breathing zone were the highest inside the vehicle (1.5 +/- 0.7 mg/m3), and the lowest in the center of the workshop (0.2 +/- 0.05 mg/m3). Since the filter size was 0.8 microm, it is possible that these values may be likely an underestimation of the true manganese levels. Serum levels of manganese and iron in welders were about three-fold (p < 0.01) and 1.2-fold (p < 0.01), respectively, higher than those of controls. Serum concentrations of ferritin and transferrin were increased among welders, while serum transferrin receptor levels were significantly decreased in comparison to controls. Linear regression analyses revealed a lack of association between serum levels of manganese and iron. However, serum concentrations of iron and ferritin were positively associated with years of welder experience (p < 0.05). Moreover, serum transferrin receptor levels were inversely associated with serum manganese concentrations (p < 0.05). These findings suggest that exposure to welding fume among welders disturbs serum homeostasis of manganese, iron, and the proteins associated with iron metabolism. Serum manganese may serve as a reasonable biomarker for assessment of recent exposure to airborne manganese.

Amyotrophic lateral sclerosis (ALS), a novel rare cause of elevated plasma troponin T levels.

PubMed

Von Lueder, Thomas G; Melsom, Morten Nissen; Atar, Dan; Agewall, Stefan

2011-01-01

In this article, we report on a patient with chronic and modestly elevated plasma troponin T (TnT) levels and frequent hospitalizations following the first admission until his death one year later. The patient was initially admitted for dyspnea and discharged from hospital with a diagnosis of non-ST elevation acute myocardial infarction (AMI). Coronary angiography and echocardiography were normal, but the patient received the (false) diagnosis of AMI at two further admissions, based purely on elevated TnT. Shortly thereafter, severe respiratory failure with restrictive-type spirometry pattern became the predominant clinical symptom, with constantly elevated TnT levels at frequent re-admissions. Due to inconsistent follow-up by primarily junior and non-specialist staff at a number of different wards, pulmonary function tests and previous smoking history were mis-interpreted as typical of chronic obstructive pulmonary disease (COPD). The patient received standard COPD treatment without any improvement. After a year of gradually worsening respiratory failure and repeated hospitalizations, thorough assessment by a pulmonologist and neurologist established the final diagnosis of amyotrophic lateral sclerosis (ALS). The patient died shortly thereafter. While progressive respiratory failure is well-known to determine morbidity and mortality in patients with ALS, chronically elevated TnT levels in the absence of coronary artery disease have, to our best knowledge, not been described so far. We suggest that chronic myocardial hypoxia due to ALS-related hypoxic respiratory failure was the most likely underlying etiology for the elevated TnT levels seen here but other mechanism such as immune-mediated myocardial injury cannot be excluded.

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

Elevated serum RANTES chemokine levels in autoimmune Addison disease.

PubMed

Fichna, Marta; Żurawek, Magdalena; Budny, Bartłomiej; Komarowska, Hanna; Niechciał, Elżbieta; Fichna, Piotr; Ruchała, Marek

2018-04-30

INTRODUCTION    Regulated on activation, normal T‑cell expressed and secreted chemokine (RANTES), the product of the CCL5 gene, is involved in trafficking immune cells into the inflammation site. It acts as coactivator of T cells and promotes polarization of the immune response towards the Th1 profile. In autoimmune Addison disease (AAD), the adrenal cortex is gradually destroyed by adrenal‑specific immune cell infiltration. RANTES might be implicated in autoimmune adrenal failure through recruitment and activation of the immune cells. Furthermore, the promoter CCL5 variant, rs2107538, seems to be associated with autoimmune endocrine conditions: diabetes and thyroid disease. OBJECTIVES    Our analysis was designed to evaluate the prevalence of rs2107538 and serum RANTES levels in AAD. PATIENTS AND METHODS    rs2107538 was genotyped using TaqMan technology in 239 individuals with AAD and 542 controls, while serum RANTES levels were evaluated by an enzyme‑linked immunosorbent assay in 114 patients with AAD and 111 healthy age- and sex‑matched individuals. RESULTS    No differences were found in rs2107538 genotype or allele frequencies between patients and controls (P = 0.53 and P = 0.39, respectively), and no association was detected with age at AAD onset (P = 0.14). Serum RANTES levels were elevated in patients with AAD compared with controls (mean [SD], 59.2 [30.3] ng/ml vs 45.5 [20.4] ng/ml, P = 0.001). Healthy carriers of various rs2107538 genotypes demonstrated differences in serum RANTES levels (P = 0.02), whereas AAD patients did not (P = 0.26). No correlation was found between circulating RANTES levels and age, AAD duration, serum autoantibodies, hydrocortisone dose, and body mass (P >0.05). CONCLUSIONS    This study demonstrates for the first time elevated serum RANTES levels in AAD and confirms that rs2107538 may affect serum chemokine levels.

Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control

NASA Astrophysics Data System (ADS)

Guaraldo, Michela; Santambrogio, Paolo; Rovelli, Elisabetta; di Savino, Augusta; Saglio, Giuseppe; Cittaro, Davide; Roetto, Antonella; Levi, Sonia

2016-09-01

Mitochondrial ferritin (FtMt) is an iron storage protein belonging to the ferritin family but, unlike the cytosolic ferritin, it has an iron-unrelated restricted tissue expression. FtMt appears to be preferentially expressed in cell types characterized by high metabolic activity and oxygen consumption, suggesting a role in protecting mitochondria from iron-dependent oxidative damage. The human gene (FTMT) is intronless and its promoter region has not been described yet. To analyze the regulatory mechanisms controlling FTMT expression, we characterized the 5‧ flanking region upstream the transcriptional starting site of FTMT by in silico enquiry of sequences conservation, DNA deletion analysis, and ChIP assay. The data revealed a minimal promoter region and identified the presence of SP1, CREB and YY1 as positive regulators, and GATA2, FoxA1 and C/EBPβ as inhibitors of the transcriptional regulation. Furthermore, the FTMT transcription is increased by acetylating and de-methylating agent treatments in K562 and HeLa cells. These treatments up-regulate FtMt expression even in fibroblasts derived from a Friedreich ataxia patient, where it might exert a beneficial effect against mitochondrial oxidative damage. The expression of FTMT appears regulated by a complex mechanism involving epigenetic events and interplay between transcription factors.

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

PubMed

Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

2011-11-01

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

[Children with hyperthyroidism due to elevated hCG levels].

PubMed

Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

2014-01-01

We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

EPA Science Inventory

Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

Arsenic causes cancer in human skin, urinary bladder, lung, liver and kidney and is a significant world-wide public health problem. Although the metabolism of inorganic arsenic is ...

Elevated lipoprotein (a) levels are an independent risk factor for retinal vein occlusion.

PubMed

Kuhli-Hattenbach, Claudia; Miesbach, Wolfgang; Lüchtenberg, Marc; Kohnen, Thomas; Hattenbach, Lars-Olof

2017-03-01

To investigate the prevalence of lipoprotein (a) [Lp(a)] and other thrombophilic disorders among retinal vein occlusion (RVO) patients with regard to age and various risk factors. We retrospectively reviewed the medical records of 100 patients with central, hemicentral or branch RVO who had undergone routine thrombophilia screening. Data were compared with 100 controls. Both cohorts were divided into three subgroups (≤45 years, >45-≤60 years or >60 years), depending on the patients' age at the time of the RVO or a previous thromboembolic event. Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients than among controls (p < 0.0001; OR: 4.8). Moreover, we determined age ≤60 years by the time of the first thromboembolic event as a strong predictor of elevated Lp(a) (p = 0.0002). The coincidence of elevated Lp(a) with other coagulation disorders further increased the OR for RVO to 9.3 (95% CI 2.1-41.8). Multivariate analysis revealed the presence of cardiovascular risk factors (OR: 3.1, p = 0.0004), elevated lipoprotein (a) levels (OR: 5.2, p = 0.0001) and increased factor VIII activity (OR: 5.9, p = 0.001) as independent risk factors for the development of RVO among patients. Our results indicate that elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a). © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Tidal marsh plant responses to elevated CO2 , nitrogen fertilization, and sea level rise.

PubMed

Adam Langley, J; Mozdzer, Thomas J; Shepard, Katherine A; Hagerty, Shannon B; Patrick Megonigal, J

2013-05-01

Elevated CO2 and nitrogen (N) addition directly affect plant productivity and the mechanisms that allow tidal marshes to maintain a constant elevation relative to sea level, but it remains unknown how these global change drivers modify marsh plant response to sea level rise. Here we manipulated factorial combinations of CO2 concentration (two levels), N availability (two levels) and relative sea level (six levels) using in situ mesocosms containing a tidal marsh community composed of a sedge, Schoenoplectus americanus, and a grass, Spartina patens. Our objective is to determine, if elevated CO2 and N alter the growth and persistence of these plants in coastal ecosystems facing rising sea levels. After two growing seasons, we found that N addition enhanced plant growth particularly at sea levels where plants were most stressed by flooding (114% stimulation in the + 10 cm treatment), and N effects were generally larger in combination with elevated CO2 (288% stimulation). N fertilization shifted the optimal productivity of S. patens to a higher sea level, but did not confer S. patens an enhanced ability to tolerate sea level rise. S. americanus responded strongly to N only in the higher sea level treatments that excluded S. patens. Interestingly, addition of N, which has been suggested to accelerate marsh loss, may afford some marsh plants, such as the widespread sedge, S. americanus, the enhanced ability to tolerate inundation. However, if chronic N pollution reduces the availability of propagules of S. americanus or other flood-tolerant species on the landscape scale, this shift in species dominance could render tidal marshes more susceptible to marsh collapse. © 2013 Blackwell Publishing Ltd.

Concholepas concholepas Ferritin H-like subunit (CcFer): Molecular characterization and single nucleotide polymorphism associated to innate immune response.

PubMed

Chávez-Mardones, Jacqueline; Valenzuela-Muñoz, Valentina; Núñez-Acuña, Gustavo; Maldonado-Aguayo, Waleska; Gallardo-Escárate, Cristian

2013-09-01

Ferritin has been identified as the principal protein of iron storage and iron detoxification, playing a pivotal role for the cellular homeostasis in living organisms. However, recent studies in marine invertebrates have suggested its association with innate immune system. In the present study, one Ferritin subunit was identified from the gastropod Concholepas concholepas (CcFer), which was fully characterized by Rapid Amplification of cDNA Ends technique. Simultaneously, a challenge test was performed to evaluate the immune response against Vibrio anguillarum. The full length of cDNA Ccfer was 1030 bp, containing 513 bp of open reading frame that encodes to 170 amino acid peptide, which was similar to the Ferritin H subunit described in vertebrates. Untranslated Regions (UTRs) were identified with a 5'UTR of 244 bp that contains iron responsive element (IRE), and a 3'UTR of 273 bp. The predicted molecular mass of deduced amino acid of CcFer was 19.66 kDa and isoelectric point of 4.92. Gene transcription analysis revealed that CcFer increases against infections with V. anguillarum, showing a peak expression at 6 h post-infection. Moreover, a single nucleotide polymorphism was detected at -64 downstream 5'UTR sequence (SNP-64). Quantitative real time analysis showed that homozygous mutant allele (TT) was significantly associated with higher expression levels of the challenged group compared to wild (CC) and heterozygous (CT) variants. Our findings suggest that CcFer is associated to innate immune response in C. concholepas and that the presence of SNPs may involve differential transcriptional expression of CcFer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assembly of Modified Ferritin Proteins on Carbon Nanotubes and its Electrocatalytic Activity for Oxygen Reduction

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Lillehei, Peter T.; Park, Cheol

2012-01-01

Highly effective dispersions of carbon nanotubes (CNTs) can be made using a commercially available buffer solution. Buffer solutions of 3-(N-morpholino)-propanesulfonic acid (MOPS), which consists of a cyclic ring with nitrogen and oxygen heteroatoms, a charged group, and an alkyl chain greatly enhance the dispersibility and stability of CNTs in aqueous solutions. Additionally, the ability of biomolecules, especially cationized Pt-cored ferritins, to adhere onto the well-dispersed CNTs in the aqueous buffer solution is also improved. This was accomplished without the use of surfactant molecules, which are detrimental to the electrical, mechanical, and other physical properties of the resulting products. The assembled Pt-cored ferritin proteins on the CNTs were used as an electrocatalyst for oxygen reduction

Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eid, Rawan; Department of Biology, Queen's University, Kingston, Ontario; Boucher, Eric

Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomycesmore » cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in

Elevated ground-level O(3) changes the diversity of anoxygenic purple phototrophic bacteria in paddy field.

PubMed

Feng, Youzhi; Lin, Xiangui; Yu, Yongchang; Zhu, Jianguo

2011-11-01

The knowledge of the impact of elevated ground-level O(3) below ground the agro-ecosystem is limited. A field experiment in China Ozone Free-Air Concentration Enrichment (FACE-O(3)) facility on a rice-wheat rotation system was carried out to investigate responses of anoxygenic phototrophic purple bacteria (AnPPB) to elevated ground-level O(3). AnPPB community structures and sizes in paddy soil were monitored by molecular approaches including PCR-DGGE and real-time quantitative PCR based upon the pufM gene on three typical rice growth stages. Repetitive sequence-based PCR (rep-PCR) in combination with culture-reliant method was conducted to reveal changes in genotypic diversity. Elevated ground-level O(3) statistically reduce AnPPB abundance and percentage in total bacterial community in flooded rice soil via decreasing their genotypic diversity and metabolic versatility. Concomitantly, their community composition changed after rice anthesis stage under elevated ground-level O(3). Our results from AnPPB potential responses imply that continuously elevated ground-level O(3) in the future would eventually harm the health of paddy ecosystem through negative effect on soil microorganisms.

Impact of the serum ferritin concentration in liver transplantation.

PubMed

Wakiya, Taiichi; Sanada, Yukihiro; Urahashi, Taizen; Ihara, Yoshiyuki; Yamada, Naoya; Okada, Noriki; Hirata, Yuta; Hakamada, Kenichi; Yasuda, Yoshikazu; Mizuta, Koichi

2015-11-01

The serum ferritin (SF) concentration is a widely available and objective laboratory parameter. SF is also widely recognized as an acute-phase reactant. The purpose of the present study was to identify the chronological changes in the recipient's SF concentration during liver transplantation (LT) and to clarify factors having an effect on the recipient's intraoperative SF level. In addition, the study retrospectively evaluated the usefulness of measuring SF during LT. Ninety-eight pediatric recipients were retrospectively analyzed. The data were analyzed and compared according to the SF level in the recipient. Patients were classified into 2 groups based on the intraoperative peak SF levels of ≤ 1000 ng/mL (low-SF group) or >1000 ng/mL (high-SF group). The SF value increased dramatically after reperfusion and fell to normal levels within the early postoperative period. The warm ischemia time (WIT) was significantly longer in the high-SF group (47.0 versus 58.5 minutes; P = 0.003). In addition, a significant positive correlation was observed between the peak SF value and WIT (r = 0.35; P < 0.001). There were significant positive correlations between the peak SF value and the donors' preoperative laboratory data, including transaminases, cholinesterase, hemoglobin, transferrin saturation, and SF, of which SF showed the strongest positive correlation (r = 0.74; P < 0.001). The multivariate analysis revealed that WIT and donor's SF level were a significant risk factor for high SF level in the recipient (P = 0.007 and 0.02, respectively). In conclusion, the SF measurement can suggest the degree of ischemia/reperfusion injury (IRI). A high SF level in the donor is associated with the risk of further acute reactions, such as IRI, in the recipient. © 2015 American Association for the Study of Liver Diseases.

ARSENIC SPECIES THAT CAUSE RELEASE OF IRON FROM FERRITIN AND GENERATION OF ACTIVATED OXYGEN

EPA Science Inventory

ABSTRACT

The in vitro effects of four different species of arsenic { arsenate, arsenite, monomethylarsonic acid and dimethylarsinic acid) in mobilizing iron from horse spleen ferritin under aerobic and anaerobic conditions were investigated. Dimethylarsinicacid {DMA(V...

Hepatic iron content is independently associated with serum hepcidin levels in subjects with obesity.

PubMed

Moreno-Navarrete, José María; Moreno, María; Puig, Josep; Blasco, Gerard; Ortega, Francisco; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel

2017-10-01

Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed. Serum hepcidin, ferritin and hepatic iron content (HIC) were significantly increased in participants with obesity. Age- and gender-adjusted serum hepcidin was positively correlated with BMI, hsCRP, ferritin and HIC. In addition, age- and gender-adjusted serum hepcidin was positively correlated with ferritin and HIC in both non-obese and obese participants. In multivariate regression analysis, hepatic iron content (p < 0.01) and serum ferritin (p < 0.001) contributed independently to circulating hepcidin concentration variation after controlling for age, gender, BMI and hsCRP. Diet intervention-induced weight loss led to decreased serum hepcidin (p = 0.01), serum ferritin concentration (p = 0.01) and HIC (p = 0.002). Of note, the percent change of serum hepcidin strongly correlated with the percent change of serum ferritin (r = 0.69, p = 0.01) and HIC (r = 0.61, p = 0.03) even after controlling for age and gender. Serum hepcidin is a reliable marker of the hepatic iron content in subjects with obesity. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The role of nonconserved residues of Archaeoglobus fulgidus ferritin on its unique structure and biophysical properties.