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

A series of specific macromolecules (tetanus toxin, cholera toxin, nerve growth factor [NGF], and several lectins) have been shown to be transported retrogradely with high selectivity from terminals to cell bodies in various types of neurons. Under identical experimental conditions (low protein concentrations injected), most other macromolecules, e.g. horseradish peroxidase (HRP), albumin, ferritin, are not transported in detectable amounts. In the present EM study, we demonstrate selective binding of tetanus toxin to the surface membrane of nerve terminals, followed by uptake and subsequent retorgrade axonal transport. Tetanus toxin or albumin was adsorbed to colloidal gold particles (diam 200 A). The complex was shown to be stable and well suited as an EM tracer. 1-4 h after injection into the anterior eye chamber of adult rats, tetanus toxin-gold particles were found to be selectively associated with membranes of nerve terminals and preterminal axons. Inside terminals and axons, the tracer was localized mainly in smooth endoplasmic reticulum (SER)-like membrane compartments. In contrast, association of albumin-gold complexes with nervous structures was never observed, in spite of extensive uptake into fibroblasts. Electron microscope and biochemical experiments showed selective retrograde transport of tetanus toxin-gold complexes to the superior cervical ganglion. Specific binding to membrane components at nerve terminals and subsequent internalization and retrograde transport may represent an important pathway for macromolecules carrying information from target organs to the perikarya of their innervating neurons.
 ...
PMID:Selective binding, uptake, and retrograde transport of tetanus toxin by nerve terminals in the rat iris. An electron microscope study using colloidal gold as a tracer. 65 8

Distribution of alpha-D-mannose and alpha-D-glucose residues of glycoconjugates in axons of sciatic nerves of 24-month old rats of Wistar strains was studied by concanavalin-A-ferritin conjugate. In some of axons there were cumulations of ferritin molecules in agglomerates of various size with polarization of the phenomenon at preserved integrity of myelin sheath. In other cases the concentration of a large number of lectin binding sites was established in the region of the degenerating part of myelin sheath, engrossed in the axon cylinder. The changes in the distribution of carbohydrate residues in the axoplasm of some of the fibers are discussed in connection with the occurring axonal atrophy in fibers of peripheral nerves of old rats.
 ...
PMID:[Cytochemical localization of concanavalin A binding sites in the peripheral nerve axons of old rats]. 239 17

Endocytosis by rods of the rat retina was studied at the ultrastructural level with cationized ferritin. Endocytosed ferritin was found within all photoreceptor subdivisions except the outer segment. Within the cell, synaptic vesicles, lysosomes and a variety of other membrane-bound organelles including the axonal agranular reticulum contained ferritin. These findings indicate that surface membrane and materials bound to surface membrane are recycled to form synaptic vesicles, that a portion of the captured membrane and extracellular material enters a lysosomal pathway, and that endocytosed materials can be retrogradely transported to the myoid region of the photoreceptor.
 ...
PMID:Endocytosis of cationized ferritin by rat photoreceptors. 258 31

We have examined the effect of the trophic protein, nerve growth factor (NGF), on organotypic cultures of fetal rat striatum. Treatment of cultures with NGF for 10-11 days resulted in a 5- to 12-fold increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT; EC 2.3.1.6). in a dose-dependent fashion. This effect was not elicited by insulin, ferritin, or cytochrome c, proteins similar in structure or physicochemical properties to NGF. The effect of NGF on CAT activity was specifically blocked by anti-NGF antiserum, whereas treatment with the antiserum alone did not have a significant effect on the enzyme. Immunocytochemical studies of the treated cultures, using a monoclonal antibody directed against CAT, revealed positively stained neurons exhibiting dendritic and axonal processes. NGF did not have an effect on total protein content of the striatal cultures, suggesting a highly specific effect. Moreover, levels of substance P, a peptide localized to other, noncholinergic neurons, were not altered by NGF. Substance P remained unchanged after treatment with NGF for 12 days, whereas CAT activity increased 12-fold in sister cultures. Although the mechanisms of action of NGF on striatal cholinergic interneurons remain to be determined, the marked, specific response of CAT suggests that this well-defined trophic protein may play a critical role in normal brain development.
 ...
PMID:Nerve growth factor promotes cholinergic development in brain striatal cultures. 386 96

The distribution of polycationic and polyanionic binding sites in the electric organ of Torpedo marmorata was investigated by incubation of tissue with native (NF) ferritin. 1) Collagen fibrils from the electric organ carry rosettes of polyanionic sites on their surface with a periodicity of 60 nm, corresponding to the pattern of crossbanding in collagen fibrils. The CF-binding sites are abut 30 nm in size and project 20 nm beyond the surface of the fibril. 2) As revealed by incubation of tissue homogenates, CF heavily stains the intraperiod line of the axonal myelin and also tubular structures in the axonal cytoplasm. 3) Neither the extracellular aspects of the pre- nor the postsynaptic membrane became labeled with either NF or CF. After incubation of tissue homogenates. labeling of the electron-dense material of the cytoplasmic aspect of the postsynaptic membrane was observed with NF and, in particular, with CF. The ventral basal lamina of the electroplaque cell revealed uniform labeling with NF. In contrast, CF-binding sites were distributed in the lamina densa of the basal lamina as a lattice of discrete binding sites, approximately 45 nm in diameter. The presence of polyanionic sites in the basal lamina, which also proceeds through the synaptic cleft, suggests the existence of a diffusion barrier for the released neurotransmitter acetylcholine. It is proposed that this facilitates hydrolysis of acetylcholine in the synaptic cleft and recirculation of the products of hydrolysis to the axon terminal.
 ...
PMID:Binding of cationized and native ferritin to cellular structures of the electric organ of Torpedo marmorata. 685 Jul 61

To investigate further the selectivity of retrograde axonal transport of horseradish peroxidase (HRP) isoenzymes previously observed in the rat central visual pathways, cultured mouse neuroblastoma cells (clone N18) were examined for selectivity of endocytosis of peroxidases and cationized ferritin in vitro. Differentiating N18 cells were incubated with proteins in various timing and pulse-chase experiments, and examined for the ultrastructural localization of endocytosed protein using cytochemical techniques. Semi-quantitative morphometry was performed on some of the samples. Major findings were as follows. (1) The protein was internalized into vesicles (coated and uncoated), short tubules and occasional small cup-shaped bodies within the first few minutes, and transferred via tubules and uncoated vesicles to secondary lysosome-like organelles (vacuoles, multivesicular bodies and dense bodies) from 5 to 15 min, with dense bodies representing the final site of protein accumulation. All the proteins tested were endocytosed through the same pathways in the soma and neurite of the cell. (2) There was no indication of a net orthograde or retrograde neuritic transport proteins. (3) There were induced increases in both vesicle and tubule formation as a result of protein endocytosis, with HRP isoenzyme C showing the greatest effect. (4) The apparent rate of internalization of HRP isoenzyme C into vesicles during the initial 5 min was significantly greater than for other peroxidases amd cationized ferritim. (5) Relatively more tubules than vesicles were involved in the uptake of protein as endocytosis was prolonged from 5 min to 8 h, with HRP isoenzyme C showing the largest effect. (6) There were indications of preferential compartmentation of endocytosed protein into certain organelles.
 ...
PMID:Endocytosis and compartmentation of peroxidases and cationized ferritin in neuroblastoma cells. 744 Dec 98

The present study provides evidence for anterograde axonal transport of manganese (Mn) in the basal ganglia. Microinjections of 54Mn into rat substantia nigra or striatum revealed region-specific accumulation and retention of the isotope in globus pallidus, striatum, thalamus and substantia nigra for up to at least 48 or 72 h respectively. Within 4 h after intrastriatal injection of 54Mn, radioactivity accumulated in the substantia nigra, suggesting axonal transport of the metal. Subsequent studies using bilateral 54Mn injections into striatum or substantia nigra and unilateral colchicine injections into or transection of the medial forebrain bundle confirmed axonal transport of Mn through these fibres. Selective destruction of the striatonigral or nigrostriatal pathways using quinolinic acid or 6-hydroxydopamine 2 weeks before injection of the isotope, revealed uptake of 54Mn by cell bodies of both gamma-aminobutyric acidergic striatal and dopaminergic nigral neurons and subsequent anterograde transport through striatonigral or nigrostriatal fibres. In addition, the quinolinic acid-lesioned striatum retained three times more radioactivity than the intact striatum. In conclusion, the present data suggest that both glial cells and striatonigral and nigrostriatal neurons are potential targets for Mn toxicity. These results and the selective neurotoxicity of Mn are discussed with respect to the iron transport protein transferrin, transferrin receptors, the iron storage protein ferritin, and mitochondrial dysfunction.
 ...
PMID:Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia. 782 Jun 9

Transgenic mice, named GFAP-IL6, that express interleukin-6 in astrocytes in the central nervous system (CNS) have a constitutive blood-brain barrier (BBB) defect and develop a progressive neurodegenerative disease. Based on ultrastructural observations showing electron-dense pigment in the brain of the GFAP-IL6 mice, we hypothesized that iron metabolism was altered in the brains of these animals. Enhanced histochemical methods revealed abnormal iron deposition in the cerebellum from 1 month of age that worsened with progression of the disease. Immunohistochemical analysis of iron-binding proteins (IBP) showed increased ferritin immunoreactivity and a decreased signal from the transferrin receptor in symptomatic animals. Atomic absorption spectroscopy revealed a 40% increase of total iron concentration in the cerebellum at the symptomatic stage. In order to obtain evidence that accumulation of this oxidizing metal was toxic, we looked for the presence of oxidative damage. Using the MAL-2 antibody, extensive lipid peroxidation (LP) was detected in the neocortex and the cerebellum in symptomatic animals. Ultrastructural analysis indicated lipofuscin deposition at the sites of neuro-axonal degeneration and abnormal iron deposition. These results suggest that the IL6-induced BBB defect precipitates iron accumulation in the GFAP-IL6 mouse brain and that subsequent IBP regulation mediates protective responses. As these defenses become overwhelmed, the iron overload seems to promote LP, which may contribute to the neurodegeneration that ensues. This transgenic mouse model of IL6-mediated neurodegeneration provides a unique opportunity to examine several aspects of iron metabolism in the brain, including its entry at the site of the BBB, its distribution through the IBP, and its mechanisms of toxicity.
 ...
PMID:Abnormal iron deposition associated with lipid peroxidation in transgenic mice expressing interleukin-6 in the brain. 960 Feb 19

Although studies using magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients have focused on findings in the white matter because of its demyelination pathogenesis, Drayer et al. have reported a high incidence of low signal intensity on T2 weighted MR imaging (MRI) in gray matter such as the thalamus and putamen. In Japan there has been no investigation of MRI findings of the basal ganglia in MS patients. Therefore, we attempted to examine the incidence and clinical significance of the imaging phenomenon in 34 Japanese patients with MS (12 male, 22 female, ages 18-54 years). As it is well known that the spinal cord and optic nerves are more frequently involved in MS than the brain in Japanese patients, we divided the patients into two subgroups based on their clinical features and the major sites of demyelination on MRI. One group included the 17 patients whose demyelinations occurred in the brain (brain-type), and the other group included the 17 patients whose abnormalities were found in the spinal cord with or without optic nerve involvement (non-brain type). As a control, MRI studies were also performed in age-matched patients with headache without any neurological signs. On T2 weighted MRI, decreased signal intensity in the thalamus was found in only four patients with MS, 11.8% of the total number examined, and in the putamen in three patients with MS, 8.8% of the total examined. All of the patients who showed abnormal decreased signal intensity in the thalamus and/or putamen belonged to the brain-type group, and these incidences were 23.5% in the thalamus and 17.6% in the putamen among the brain-type patients. No patient belonging to the non-brain type showed this imaging sign. This imaging sign was well correlated with the degree of white matter abnormalities in the brain estimated as a score according to modified Callanan et al.'s method. In addition, this sign was also correlated with the expanded disability status scales (EDSS) in the brain-type patients. These observations suggest that the axonal damages due to severe demyelination may induce the impaired transport of iron resulting in an accumulation of ferritin in the thalamus and putamen, and would cause decreased signal intensity on T2 weighted MRI. The relatively low incidence of decreased signal intensity in the thalamus and putamen in this study may be associated with differences in the clinical phenotype of MS between Japan and the USA. In brain-type patients the evaluation of basal ganglia on T2 weighted MRI may be a useful tool for estimating patients' disabilities.
 ...
PMID:[Reduced signal intensity of T2 weighted MR imaging of thalamus and putamen in multiple sclerosis in Japan]. 1118 4

In order to study the changes in axons related to acute localized physical trauma, a 25 gauge needle was inserted into the somatosensory cortex of anaesthetized adult rats. Animals were examined over 11 time points, from 30 min to 14 days postinjury. Initially, the central needle tract was surrounded by 'reactive' abnormal axons characterized by their bulb- or ring-like immunoreactivity for neurofila ments. Quantification demonstrated that these structures reached a peak density at 24 h postinjury, followed by a gradual decrease over 2 weeks. By 5 days postinjury, long axons showing high levels of neurofilament labelling were localized to the lesion area, either aligned parallel to the tract edges or extending into the bridge of tissue forming between the tract edges. Double-labelling demonstrated a close association between sprouting axons and ferritin-labelled microglia. Immunolabelling for GAP43 also demonstrated the presence of sprouting axons within this tissue bridge. Ultrastuctural examination showed that sprouting axons contained a high density of neurofilaments, with a leading edge lacking these filaments. Injury to the adult neocortex is associated with reactive and sprouting changes within axons, coordinated with the proliferation of microglia and wound healing. These data also support a role for neurofilaments in axonal sprouting following brain injury.
 ...
PMID:Alterations in neurofilaments associated with reactive brain changes and axonal sprouting following acute physical injury to the rat neocortex. 1143 92


1 2 3 Next >>