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Aguirre, Pabla; Mena, Natalia; Tapia, Victoria; Arredondo, Miguel; Núñez, Marco T.

doi:10.1186/1471-2202-6-3

Cited by 64 publications

(23 citation statements)

References 21 publications

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“…Coimmunoprecipitation of Fpn with different epitope tags, as well as the detection of a complex much larger than the monomer by size-exclusion chromatography, indicated that the functional unit of Fpn is a multimer. This result is consistent with the observation by Aguirre et al (21), who suggested that Fpn was dimeric. Coimmunoprecipitation showed that Fpn mutants could also form multimeric complexes with WT Fpn.…”

Section: Discussionsupporting

confidence: 83%

The molecular basis of ferroportin-linked hemochromatosis

Domenico

Ward

Nemeth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

205

221

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Section: Discussionsupporting

confidence: 83%

The molecular basis of ferroportin-linked hemochromatosis

Domenico

Ward

Nemeth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

205

221

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“…12,25,26 As in the periphery, Fpn1 is the sole known cellular iron exporter and plays a key role in brain iron release. 22,46 The turnover of Fpn1 is controlled by hepcidin. Injection of hepcidin into the lateral cerebral ventricle resulted in decreased Fpn1 protein content in the cerebral cortex, the hippocampus, and the striatum.…”

Section: Figmentioning

confidence: 99%

“…Mammalian cellular iron efflux is mediated by the sole iron exporter ferroportin 1 (Fpn1), a transmembrane protein. 22 The abundance of Fpn1 on the plasma membrane can be modulated by interaction with its ligand hepcidin, an iron regulatory hormone produced in the liver in response to inflammatory stimuli, iron, and hypoxia. 23 Hepcidin binds to Fpn1 and induces its internalization and degradation, resulting in decreased cellular iron export and subsequent iron acuumulation.…”

Section: Introductionmentioning

confidence: 99%

Calorie Restriction Down-Regulates Expression of the Iron Regulatory Hormone Hepcidin in Normal and d-Galactose–Induced Aging Mouse Brain

Wei

Shi²,

Li³

et al. 2014

Rejuvenation Research

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It has been shown that iron progressively accumulates in the brain with age. Calorie restriction (CR) may allay many of the adverse effects of aging on the brain, yet the underlying mechanisms, in particular in relation to brain iron metabolism, remain unclear. This study aimed to investigate the role of CR in the regulation of cerebral cellular iron homeostasis. C57BL/6 mice were randomly divided into four groups of eight. The control group was fed a conventional diet ad libitum; the CR group received 70% of the calories of the control mouse intake per day; the d-galactose (d-gal) group received subcutaneous injection of d-gal at a dose of 100 mg/kg once daily to produce mouse model of aging; the d-gal plus CR group received both of the two interventions for 14 weeks. The Morris water maze (MWM) was employed to test the cognitive performance of all animals, and the expression of iron regulatory genes, ferroportin and hepcidin, in the cortex and hippocampus were detected by quantitative real-time PCR. Compared to the controls, the d-gal group mice showed significant spatial reference memory deficits in the MWM test, whereas the d-gal-CR group mice exhibited almost normal cognitive function, indicating that CR protects against d-gal-induced learning and memory impairment. Hepcidin mRNA expression was increased in the d-gal group, decreased in the CR group, and was basically unchanged in the d-gal-CR group. There was no statistical difference in the transmembrane iron exporter ferroportin expression between control and any of the experimental groups. The results suggest that the antiaging effects of CR might partially lie in its capacity to reduce or avoid age-related iron accumulation in the brain through down-regulating expression of brain hepcidin-the key negative regulator for intracellular iron efflux-and that facilitating the balance of brain iron metabolism may be a promising anti-aging measure.

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“…Western Blot Analysis-Cells extracts were prepared as described (30). Proteins were resolved in 10% Laemmli SDSpolyacrylamide gels, transferred to polyvinylidene fluoride membranes (Millipore Corp.), and incubated overnight with primary antibody.…”

Section: Methodsmentioning

confidence: 99%

Iron Mediates N-Methyl-d-aspartate Receptor-dependent Stimulation of Calcium-induced Pathways and Hippocampal Synaptic Plasticity

Muñoz

Humeres

Elgueta

et al. 2011

Journal of Biological Chemistry

111

119

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Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist Nmethyl-D-aspartate (NMDA), and the effects of iron addition/ chelation on hippocampal basal synaptic transmission and longterm potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodinereduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP.Iron deficiency during early life is associated with significantly lower cognitive and behavioral infant development (1-3), severe deterioration of hippocampal neuronal function (4 -6), and poor memory and spatial learning capabilities (7-9). Current understanding of the relationship between neuronal function and brain iron status is sparse, and the molecular mechanisms underlying the essential role of iron in neuronal function remain mostly unidentified. Nonetheless, a role for iron in synaptic plasticity and the associated generation of postsynaptic Ca 2ϩ signals has begun to emerge (10 -12). Neurons obtain iron via transferrin-dependent and -independent uptake pathways. The iron concentration in cerebrospinal fluid is sufficient to saturate the binding capacity of transferrin (13). This feature highlights the need for transferrin-independent iron uptake, which is likely to occur in neurons that express the iron transporter DMT1, such as hippocampal pyramidal and granule cells, cerebellar granule cells, pyramidal cells of the piriform cortex, substantia nigra, and the ventral ...

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Cited by 64 publications

References 21 publications

The molecular basis of ferroportin-linked hemochromatosis

The molecular basis of ferroportin-linked hemochromatosis

Calorie Restriction Down-Regulates Expression of the Iron Regulatory Hormone Hepcidin in Normal and d-Galactose–Induced Aging Mouse Brain

Iron Mediates N-Methyl-d-aspartate Receptor-dependent Stimulation of Calcium-induced Pathways and Hippocampal Synaptic Plasticity

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