Characterization and Distribution of Ferritin Binding Sites in the Adult Mouse Brain

Hulet, Stanley W.; Hess, Ellen J.; Debinski, Waldemar; Arosio, Paolo; Bruce, Kady S.; Powers, Stephen K.; Connor, James R.

doi:10.1046/j.1471-4159.1999.720868.x

Cited by 76 publications

(66 citation statements)

References 47 publications

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“…These ®ndings imply that there might be some other mechanisms involved in the regulation of maternal-fetal iron transport. Previous studies have demonstrated that FnR, in addition to TfR, is present on the membranes of many normal cells (Moss et al, 1992), including reticulocytes (Blight and Morgan, 1987a), lymphoblasts (Adams et al, 1992), liver (Moss et al, 1988) and brain cells (Adams et al, 1992;Ramm et al, 1994;Hulet et al 1999). This protein is also found to play a role in iron transport across the membrane of these cells (Blight and Morgan, 1987b;Moss et al, 1988;Osterloh & Aisen, 1989;Gelvan et al, 1996) and ferritin uptake by human erythroid precursors is a regulated iron The results are meansAE s.d.…”

Section: Discussionmentioning

confidence: 99%

Expression of ferritin receptor in placental microvilli membrane in pregnant women with different iron status at mid-term gestation

et al. 2001

Eur J Clin Nutr

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Objective: The effect of iron status in pregnant women on expression of ferritin receptor in placental microvilli membrane at mid-term gestation was investigated. Design: Ferritin receptor binding sites and dissociation constants (K d ) were determined in specimens of placental microvilli from 30 pregnant women at mid-term gestation and six women at term-delivery. Results: The ferritin receptor binding sites in the placental microvilli membrane in pregnant women with mild iron de®ciency and moderate iron de®ciency anemia were signi®cantly higher then those in pregnant women with normal iron status. However, no signi®cant difference was found between pregnant women with severe iron de®ciency anemia and with normal measurements. No signi®cant differences of K d values were detected between pregnant women with normal iron status and those with iron-de®ciency. Data also revealed that the ferritin receptor binding sites in placental microvilli membrane and K d values at mid-term gestation did not differ signi®cantly from those at term gestation. Conclusion: Lower iron status in pregnant women could lead to an increase in expression of ferritin receptor in placental microvilli membrane at mid-term gestation while the dissociation constant of ferritin receptor remains unchanged. This implies that the regulation of maternal ± fetal iron homeostasis via the ferritin receptor-mediated pathway is achieved by changes in the numbers of ferritin receptors rather then binding properties. Sponsorship: China Natural Science Foundation and The Hong Kong Polytechnic University. Descriptors: ferritin receptor; placental microvilli; iron status; pregnant women; maternal-fetal iron homeostasis

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Section: Discussionmentioning

confidence: 99%

Expression of ferritin receptor in placental microvilli membrane in pregnant women with different iron status at mid-term gestation

et al. 2001

Eur J Clin Nutr

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“…The homogenate was centrifuged at 29,000 g for 10 min at 4°C. The resulting supernatant was aspirated and the pellet (representing the membranes) was resuspended with the original volume of buffer and then placed in a 37°C incubator for 30 min to promote the release of endogenous ferritin from the tissue prepara- Hulet et al [1999a]. Each value was obtained from binding experiments on at least 3 brains (each in duplicate) and is expressed as the mean B standard error.…”

Section: Membrane Preparationmentioning

confidence: 99%

Ferritin Binding in the Developing Mouse Brain Follows a Pattern Similar to Myelination and Is Unaffected by the Jimpy Mutation

Hulet

Menzies

Connor³

2002

Dev Neurosci

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We have previously provided evidence that ferritin binds selectively to white matter tracts in adult mouse and human brains. In cell culture experiments, ferritin binding is specifically localized to oligodendrocytes. The goal of the present study is to test the hypothesis that the developmental pattern for ferritin binding will coincide with the onset and progression of myelination. The first evidence of ferritin binding in the mouse brain is at 12 days of age and occurs within the brainstem. Ferritin binding persisted in the brainstem and expanded to the corpus callosum by 15–16 days of age. By 23–24 days of age ferritin binding had further extended to the striatal white matter. By adulthood, ferritin binding was strongly and selectively expressed throughout all white matter tracts. To begin to identify which factors may be involved in the induction of ferritin-binding proteins on oligodendrocytes, brains from the myelin mutant jimpy mice and unaffected littermates were examined at postnatal days 16–18. Jimpy mice were chosen because their oligodendrocytes fail to produce myelin or accumulate iron. Thus, using jimpy mice would elucidate whether these factors are necessary for ferritin-binding protein expression. Both the jimpy mutants and their controls exhibited saturable ferritin binding with similar binding densities and dissociation constants. Dissociation constants for ferritin binding in the unaffected littermates and jimpy mutant mice were 0.38 ± 0.04 and 0.32 ± 0.06 nM, respectively and binding densities were similar (1.1 ± 0.09 and 0.96 ± 0.12 fmol/mg, respectively). Our results demonstrate that expression of ferritin binding is dependent on the age of the oligodendrocytes and not dependent upon iron accumulation by oligodendrocytes or myelin production. We propose that iron delivery to oligodendrocytes is predominantly via ferritin and this method of iron uptake is unique to oligodendrocytes in the brain.

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“…[18][19][20][21][22] Evidence for the presence of a ferritin-receptor has been derived initially from cellular ferritin-binding and -uptake assays and binding of ferritin in tissue sections where binding was specific mostly for H-subunit rich ferritin. 19,[23][24][25] 21,26 and was identified in embryonic kidney and adult testis epithelial cells. 28 Early characterizations of serum ferritin were performed mainly on human serum ferritin from iron-overloaded patients.…”

Section: Introductionmentioning

confidence: 99%

“…[18][19][20][21][22] Evidence for the presence of a ferritin-receptor has been derived initially from cellular ferritin-binding and -uptake assays and binding of ferritin in tissue sections where binding was specific mostly for H-subunit rich ferritin. 19,[23][24][25] Three distinct candidates for ferritin-receptors have been characterized and cloned recently. TIM-2 26 is a murine ferritin-receptor that specifically binds H-subunit and is primarily expressed on splenic B cells, epithelial cells of the bile duct, and kidney distal tubular cells.…”

Section: Introductionmentioning

confidence: 99%

Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway

Cohen

Gutiérrez

Weiss

et al. 2010

Blood

386

324

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The serum ferritin concentration is a clinical parameter measured widely for the differential diagnosis of anemia. Its levels increase with elevations of tissue iron stores and with inflammation, but studies on cellular sources of serum ferritin as well as its subunit composition, degree of iron loading and glycosylation have given rise to conflicting results. To gain further understanding of serum ferritin, we have used traditional and modern methodologies to characterize mouse serum ferritin. We find that both splenic macrophages and proximal tubule cells of the kidney are possible cellular sources for serum ferritin and that serum ferritin is secreted by cells rather than being the product of a cytosolic leak from damaged cells. Mouse serum ferritin is composed mostly of L-subunits, whereas it contains few H-subunits and iron content is low. L-subunits of serum ferritin are frequently truncated at the C-terminus, giving rise to a characteristic 17-kD band that has been previously observed in lysosomal ferritin. Taken together with the fact that mouse serum ferritin is not detectably glycosylated, we propose that mouse serum ferritin is secreted through the nonclassical lysosomal secretory pathway. (Blood. 2010;116(9):1574-1584) IntroductionFerritin in mammals is a mostly intracellular, cytosolic iron storage and detoxification protein. It consists of H-and L-subunits that assemble into a 24-subunit hollow sphere in which iron is sequestered. 1 However, ferritin can also be detected extracellularly, in cerebrospinal fluid and sinovial fluid. In serum it is an extracellular ferritin that has been used extensively in diagnostic tests. In the clinical setting, serum ferritin evaluation is most commonly used to estimate body iron stores as low serum ferritin correlates with iron depletion, whereas high serum ferritin correlates with elevated body iron stores or with inflammation in patients with normal body iron stores. 2,3 Characterization of serum ferritin has produced many controversial results regarding subunit composition, iron content and other features. It has been compared in some studies to the "natural apoferritin" fraction found in many tissues, which is essentially devoid of iron 4 while other studies have claimed that serum ferritin contains considerable amounts of iron. 5 In insects, ferritin is a secreted protein composed of 2 types of subunits and the heteropolymer functions most likely as an iron transporter in the hemolymph. Each of the subunits has a classical secretion signal and ferritin is secreted from the insect fat body. 6 In contrast, mammalian H-and L-ferritin subunits lack signals mediating endoplasmic reticulum (ER) targeting, but ferritin can traffic to the lysosomal compartment through autophagy. 7 Binding of human serum ferritin to the lectin Concanavalin A (ConA) has previously suggested that ferritin is glycosylated 8,9 and actively secreted through the ER-Golgi pathway. 10 Indeed, it was shown in hepatocyte cell-models that inhibition of ER-Golgi trafficking abolished secretion o...

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Characterization and Distribution of Ferritin Binding Sites in the Adult Mouse Brain

Cited by 76 publications

References 47 publications

Expression of ferritin receptor in placental microvilli membrane in pregnant women with different iron status at mid-term gestation

Expression of ferritin receptor in placental microvilli membrane in pregnant women with different iron status at mid-term gestation

Ferritin Binding in the Developing Mouse Brain Follows a Pattern Similar to Myelination and Is Unaffected by the Jimpy Mutation

Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway

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