Iron and its sensitive balance in the cell

Freitas, Jeane M. De; Meneghini, Rogério

doi:10.1016/s0027-5107(01)00066-5

Cited by 86 publications

(41 citation statements)

References 57 publications

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“…This is an important observation, given the toxic effects that can be mediated by high iron exposure (De Freitas and Meneghini, 2001;Kress et al, 2002;Patel et al, 2002). Clearly, if this were to occur, then the clinical applications of this technique would be limited, despite the advantages gained by being able to visualize transplanted cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

Superparamagnetic Iron Oxide-Labeled Schwann Cells and Olfactory Ensheathing Cells Can Be TracedIn Vivoby Magnetic Resonance Imaging and Retain Functional Properties after Transplantation into the CNS

Dunning¹,

Lakatos²,

Loizou³

et al. 2004

J. Neurosci.

121

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Schwann cell (SC) and olfactory ensheathing cell (OEC) transplantation has been shown experimentally to promote CNS axonal regeneration and remyelination. To advance this technique into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Previous studies, using complex modification processes to enable uptake of contrast agents, have shown that cells labeled in vitro with paramagnetic contrast agents transplanted into rodent CNS can be visualized using magnetic resonance imaging (MRI). Here we show that SCs and OECs efficiently internalize dextran-coated superparamagnetic iron oxide (SPIO) from the culture medium by fluid phase pinocytosis. After transplantation into focal areas of demyelination in adult rat spinal cord both transplanted SPIO-labeled SCs and OECs produce a signal reduction using T 2 -weighted MRI in anesthetized rats that persists for up to 4 weeks. Although signal reduction was discernable after transplantation of unlabelled cells, this is nevertheless distinguishable from that produced by transplanted labeled cells. The region of signal reduction in SPIO-labeled cell recipients correlates closely with areas of remyelination. Because the retention of functional integrity by labeled cells is paramount, we also show that SPIO-labeled SCs and OECs are able to myelinate normally after transplantation into focal areas of demyelination. These studies demonstrate the feasibility of noninvasive imaging of transplanted SCs and OECs and represent a significant step toward the clinical application of promising experimental approaches.

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Section: Discussionmentioning

confidence: 99%

Superparamagnetic Iron Oxide-Labeled Schwann Cells and Olfactory Ensheathing Cells Can Be TracedIn Vivoby Magnetic Resonance Imaging and Retain Functional Properties after Transplantation into the CNS

Dunning¹,

Lakatos²,

Loizou³

et al. 2004

J. Neurosci.

121

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“…As often noted (1)(2)(3)(4) iron is needed in organisms in relatively large amounts. A 70-kg adult human has Ϸ5 g of iron (Ϸ10 Ϫ3 M for body volume), whereas a bacterial cell of 10 Ϫ9 cm 3 requires 10 5 to 10 6 ferric ions per generation to maintain the required 10 Ϫ6 M internal concentration (5).…”

mentioning

confidence: 93%

Enterobactin: An archetype for microbial iron transport

Raymond

Dertz

Kim

2003

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

791

692

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Bacteria have aggressive acquisition processes for iron, an essential nutrient. Siderophores are small iron chelators that facilitate cellular iron transport. The siderophore enterobactin is a triscatechol derivative of a cyclic triserine lactone. Studies of the chemistry, regulation, synthesis, recognition, and transport of enterobactin make it perhaps the best understood of the siderophore-mediated iron uptake systems, displaying a lot of function packed into this small molecule. However, recent surprises include the isolation of corynebactin, a closely related trithreonine triscatechol derivative lactone first found in Gram-positive bacteria, and the crystal structure of a ferric enterobactin complex of a protein identified as an antibacterial component of the human innate immune system.

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“…Iron circulates in the blood bound to transferrin. The principal known effectors of iron uptake and transport into the cell are the transferrin receptor (TfR) (De Freitas and Meneghini, 2001) and divalent metal transporter 1 (Nramp2) . Nramp2 shares structural and functional homology to Nramp1 (Vidal et al, 1995), and plays a role in transport of Fe +2 out of the early endosome and into the cytosol (Andrews, 1999;Canonne-Hergaux et al, 2001;Gruenheid et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

Waes

Smith

Waes

et al. 2008

Experimental Eye Research

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Microphthalmia-associated Transcription Factor (Mitf) is expressed in neural crest cell-derived melanocytes, and in the retinal pigment epithelium (RPE) during ocular development. Mutations in Mitf are associated with auditory/visual/pigmentary syndromes in humans. Mitf mi/mi mouse mutants lack pigmentation, and are microphthalmic, while Mitf vit/vit mouse mutants display abnormal RPE pigmentation, and progressive retinal degeneration. Microarray analysis was used to identify novel downstream gene targets/pathways in the RPE that are altered by mutations in the transcription factor Mitf. Using the Affymetrix platform, gene expression profiles were generated using the eyes of E13.5 mouse fetuses that were wildtype, heterozygous, or homozygous for the Mitf mi mutation. In a separate experiment, eyes from E13.5 mouse fetuses homozygous for the Mitf vit mutation were compared to eyes from the C57BL/6 control background strain. Statistical analyses were performed using Robust Multiarray Average, mixed-effects ANOVA and random-variance t-tests. Altered expression of genes involved in pigment formation, melanosome biogenesis/transport, and redox homeostasis were observed. 12 genes were commonly mis-regulated in the eyes of both Mitf mutants: 10 of these genes were downregulated in both mutants relative to controls, while 2 of the genes (Nramp1 (Slc11a1) and epoxide hydrolase) were downregulated in Mitf mi/mi mutants, and conversely, upregulated in Mitf vit/vit mutants. Quantitative RT-PCR and immunohistochemistry were used to confirm altered gene/protein expression. RPE expression of the Fe +2 iron transporter Nramp1 (Slc11a1) has not previously been reported. Fe +2 is an important co-factor utilized by the iron-dependent isomerohydrolase RPE65 in the retinoid visual cycle. However, excess accumulation of Fe +2 in the RPE has recently been associated with oxidative damage and age-related macular degeneration. Abnormal pigmentation and increased activity of Slc11a1 in the RPE of Mitf vit mice may contribute to the pathology and progressive retinal degeneration observed in these mutants.

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Iron and its sensitive balance in the cell

Cited by 86 publications

References 57 publications

Superparamagnetic Iron Oxide-Labeled Schwann Cells and Olfactory Ensheathing Cells Can Be TracedIn Vivoby Magnetic Resonance Imaging and Retain Functional Properties after Transplantation into the CNS

Superparamagnetic Iron Oxide-Labeled Schwann Cells and Olfactory Ensheathing Cells Can Be TracedIn Vivoby Magnetic Resonance Imaging and Retain Functional Properties after Transplantation into the CNS

Enterobactin: An archetype for microbial iron transport

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

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