Abstract
AbstractThere is a critical relationship between oligodendrocyte development, myelin production, and iron bioavailability. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding molecular mechanisms of iron import into oligodendrocytes is necessary for devising effective strategies for iron supplementation. Although transferrin has been considered as an essential component of oligodendrocyte media in culture, oligodendrocytes in vivo lack transferrin receptors. We have established that receptors for H‐ferritin (HF) exist on cells of oligodendroglial lineage and that uptake of extracellular HF by oligodendrocyte progenitors is via receptor mediated endocytosis. These data strongly argue that ferritin is a major source of iron for oligodendrocytes. In this study, we demonstrate that media deficient in transferrin results in loss of viability of oligodendrocyte progenitors in culture. Cell loss could be prevented by supplementing the media with HF. Moreover, the addition of extracellular HF stimulates development of oligodendrocyte progenitor cells (OPCs) by increasing expression of myelin basic protein (MBP) and olig2 proteins without increasing their proliferation. The effect of HF on the OPCs could be mimicked by addition of membrane permeable 3,5,5‐trimethylhexanoyl ferrocene (TMH‐Fe) as an iron source to the media, but not membrane‐impermeable ferric ammonium citrate. Overall, therefore, our results demonstrate the importance of iron for OPCs viability and differentiation and identify extracellular HF as a critical source of iron for oligodendrocytes. Given that ferritin receptors, but not transferrin receptors can be demonstrated on oligodendrocytesin vivo, the delivery of iron to oligodendrocytes viaferritin may be the more biological relevant delivery system. © 2011 Wiley‐Liss, Inc.
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Dates
Type | When |
---|---|
Created | 14 years, 5 months ago (March 28, 2011, 6:43 p.m.) |
Deposited | 5 months, 3 weeks ago (March 4, 2025, 1:39 p.m.) |
Indexed | 2 months, 1 week ago (June 19, 2025, 12:09 a.m.) |
Issued | 14 years, 5 months ago (March 28, 2011) |
Published | 14 years, 5 months ago (March 28, 2011) |
Published Online | 14 years, 5 months ago (March 28, 2011) |
Published Print | 14 years, 2 months ago (June 1, 2011) |
@article{Todorich_2011, title={H‐ferritin is the major source of iron for oligodendrocytes}, volume={59}, ISSN={1098-1136}, url={http://dx.doi.org/10.1002/glia.21164}, DOI={10.1002/glia.21164}, number={6}, journal={Glia}, publisher={Wiley}, author={Todorich, Bozho and Zhang, Xuesheng and Connor, James R.}, year={2011}, month=mar, pages={927–935} }