Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In spontaneously hyperlipoproteinemic old Sprague-Dawley rats, endogenous lipoproteins (LP) in the size range of 15 to 40 nm were directly visualized within the blood vessels due to specimen mordanting with tannic acid. LP morphometric analysis at the level of the endothelium of diaphragm capillaries revealed that particles of the dimensions of low-density lipoproteins, high-density lipoproteins (HDL1), and very low density lipoproteins occur in endothelial structures involved in receptor-mediated endocytosis coated pits-vesicles, endosomes, lysosomes) and transcytosis (plasmalemmal vesicles and transendothelial channels). No such particles could be detected in the intercellular junctions. Intravenously injected cationized ferritin (CF) of pI 8.4 bound uniformly to LP forming an CF-LP complex. Examined at 5, 20, and 60 min after CF administration, the CF-LP complex was found to be taken up by endothelium only by endocytosis (adsorptive via coated pits-vesicles, and fluid phase through a fraction of plasmalemmal vesicles). CF-LP complexes are progressively accumulated within lysosomes. These findings reveal the importance of the net surface charge of macromolecular complexes for their intracellular sorting and fate.
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PMID:Interactions of endogenous lipoproteins with capillary endothelium in spontaneously hyperlipoproteinemic rats. 408 94

Prion diseases are characterized by the conversion of the normal cellular prion protein PrP(C) into a pathogenic isoform, PrP(Sc). The mechanisms involved in neuronal cell death in prion diseases are largely unknown, but accumulating evidence has demonstrated oxidative impairment along with metal imbalances in scrapie-infected brains. In this study, we report changes in cellular iron metabolism in scrapie-infected mouse neuroblastoma N2a cells (ScN2a). We detected twofold lower total cellular iron and calcein-chelatable cytosolic labile iron pool (LIP) in ScN2a cells as compared to the N2a cells. We also measured in ScN2a cells significantly lower activities of iron regulatory proteins 1 and 2 (IRP1 and IRP2, respectively), regulators of cellular iron by sensing cytosolic free iron levels and controlling posttranscriptionally the expression of the major iron transport protein transferrin receptor 1 (TfR1) and the iron sequestration protein ferritin. IRP1 and IRP2 protein levels were decreased by 40% and 50%, respectively, in ScN2a cells. TfR1 protein levels were fourfold reduced and ferritin levels were threefold reduced in ScN2a cells. TfR1 and ferritin mRNA levels were significantly reduced in ScN2a cells. ScN2a cells responded normally to iron and iron chelator treatment with respect to the activities of IRP1 and IRP2, and biosynthesis of TfR1 and ferritin. However, the activities of IRP1 and IRP2, and protein levels of TfR1 and ferritin, were still significantly lower in iron-depleted ScN2a cells as compared to the N2a cells, suggesting lower need for iron in ScN2a cells. Our results demonstrate that scrapie infection leads to changes in cellular iron metabolism, affecting both total cellular and cytosolic free iron, and the activities and expression of major regulators of cellular iron homeostasis.
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PMID:Changed iron regulation in scrapie-infected neuroblastoma cells. 1571 Feb 43

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders characterized by the accumulation in the CNS of a pathological conformer (PrP(TSE)) of the host-encoded cellular prion protein (PrP(C)). PrP(TSE) has a central role in the pathogenesis of the disease but other factors are likely involved in the pathological process. In this work we employed a multi-step proteomic approach for the identification of proteins that co-purify with the protease-resistant core of PrP(TSE) (PrP27-30) extracted from brains of hamsters with experimental scrapie. We identified ferritin, calcium/calmodulin-dependent protein kinase alpha type II, apolipoprotein E, and tubulin as the major components associated with PrP27-30 but also trace amounts of actin, cofilin, Hsp90alpha, the gamma subunit of the T-complex protein 1, glyceraldehyde 3-phosphate dehydrogenase, histones, and keratins. Whereas some of these proteins (tubulin and ferritin) are known to bind PrP, other proteins (calcium/calmodulin-dependent protein kinase alpha type II, Hsp90alpha) may associate with PrP(TSE) fibrils during disease. Apolipoprotein E and actin have been previously observed in association with PrP(TSE), whereas cofilin and actin were shown to form abnormal rods in the brain of patients with Alzheimer disease. The roles of these proteins in the development of brain lesions are still unclear and further work is needed to explain their involvement in the pathogenesis of TSEs.
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PMID:Proteomic profiling of PrP27-30-enriched preparations extracted from the brain of hamsters with experimental scrapie. 1963 40