Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.37 (CNPase)
 539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelination is an essential component of normal development in the brain. Thus, the factors which influence the onset of myelination need to be identified and monitored during development to insure adequate myelination. These factors may also play a role in remyelination attempts which occur as a result of demyelinating diseases. One factor known to be involved in myelination is iron. In this study, the cellular deposition of iron and the intracellular iron storage protein ferritin are examined in the brains of 1-month-old piglets. Ferritin consists of 2 subunits (H and L chains) which occur in different ratios in different organs. The subunits are functionally distinct so their pattern of expression at the cellular level reveals information about the iron requirement of the cell and utilization versus storage. The H subunit of ferritin is expressed in abundance in oligodendrocytes within white-matter tracts whereas the L subunit in this region is found only in endothelial cells of blood vessels. H-ferritin-positive cells occur in clearly defined patches which are scattered throughout the white-matter tracts. The cellular distribution of iron is identical to that of H ferritin. H-ferritin-positive cells are identified as oligodendrocytes on the basis of immunofluorescent colocalization with CNPase. Also, some of the H-ferritin-positive cells are positive for myelin basic protein. However, the distribution of CNPase-positive cells is more even in the white matter than the patches of H-ferritin/iron-positive cells. The relationship between H-ferritin- and CNPase-positive cells indicates that the former are oligodendrocytes, but also reveals a subset of oligodendrocytes in the white matter. The results of this study provide insight into how the intracellular iron is managed in oligodendrocytes. The factors which initiate iron uptake and ferritin expression in a select population of oligodendrocytes, and the relationship of this select population to myelinogenesis and myelin maintenance, have yet to be identified.
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PMID:The expression of ferritin subunits and iron in oligodendrocytes in neonatal porcine brains. 891 67

We previously demonstrated ferritin binding is specific to white matter in mouse and human brain tissue and is not found within Multiple Sclerotic plaques. These results suggest that ferritin receptors are selectively expressed on oligodendrocytes. The present studies were designed to test the hypothesis that oligodendrocyte progenitor cells selectively bind ferritin and internalize it by methods consistent with receptor-mediated endocytosis. Using a cell culture system enriched for oligodendrocyte progenitor cells, we determined, that oligodendrocyte progenitor cells bind ferritin in a saturable and competitive manner with a K(d) of 5 nM and a receptor density of 0.06 fmol bound/20,000 cells. FITC tagged ferritin is internalized by A2B5, O4 or CNPase expressing cells in the culture, but not by GFAP+ cells. The uptake of ferritin into the oligodendrocyte progenitors was inhibited by treating the cells with inhibitors of receptor mediated endocytosis (hypertonic medium, potassium deficient medium, ATP depletion, sulfhydryl reagents). In addition exogenous ferritin decreased iron responsive element/iron regulatory protein binding indicating that the iron within the internalized ferritin is released and contributes to the intracellular iron pool. Given the relatively high amount of iron that can be delivered via ferritin, and the selective distribution of ferritin receptors in the white matter tracts in vivo, we propose that ferritin is a major source of iron for oligodendrocytes.
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PMID:Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. 1086 99