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)

Protein-carbohydrate recognition has been found to play an important role in phagocytosis. Labelled (neo)glycoproteins were employed to comparatively analyze the histochemical pattern and ultrastructural localization of endogenous carbohydrate-binding proteins (lectins) of mononuclear macrophages and multinucleate giant cells involved in the granulomatous foreign body reaction. Sugar receptors having an affinity to simple alpha- and beta-galactoside-structures, to alpha-mannose residues, to N-acetylglucosamine, to N-acetylgalactosamine and to glucuronic acid, respectively, were detected in both cell types. However, alpha-fucoside- and beta-xyloside-specific receptors were present only in the mononuclear macrophages. Pronounced differences were seen with labelled, suitably modified glycoproteins, exposing different complex sugar parts with common beta-galactoside-termini. Among the population of multinucleate giant cells, a positive histochemical reaction was observed with mannose-6-phosphate-, galactose-6-phosphate- and glucuronic acid-(BSA-biotin), respectively, only in giant cells in which fusing mononuclear cells were recognizable. This transient expression indicates changes within the profile of endogenous sugar receptors in the stages from fusion to establishment of giant cells. Aside from the diffuse intracytoplasmic distribution of carbohydrate-binding proteins, a prominent accumulation of various types of glycosylated ferritin, used as a marker for electron microscopic evaluation, was ultrastructurally found in membranous subcellular structures and vesicles. This study is a basis for further investigation of the potential involvement of various sugar receptors in the process of macrophage fusion, resulting in multinucleate giant cells of foreign body type, and the process of phagocytosis.
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PMID:Are glycoconjugates and their endogenous receptors involved in the fusion of mononuclear macrophages resulting in multinucleate giant cells? Histochemical and electron microscopic determination of endogenous sugar-binding proteins (lectins) in mononuclear macrophages and multinucleate giant cells appearing in granulomatous foreign body reaction. 254 62

We have examined the distribution of mannose-6-phosphate (Man6P) receptors (215 kD) for lysosomal enzymes in cultured Clone 9 hepatocytes at various times after the addition or removal of lysosomotropic weak bases (chloroquine or NH4Cl). Our previous studies demonstrated that after treatment with these agents, Man6P receptors are depleted from their sorting site in the Golgi complex and accumulate in dilated vacuoles that could represent either endosomes or lysosomes (Brown, W. J., E. Constantinescu, and M. G. Farquhar, 1984, J. Cell Biol., 99:320-326). We have now investigated the nature of these vacuoles by labeling NH4Cl-treated cells simultaneously with anti-Man6P receptor IgG and lysosomal or endosomal markers. The structures in which the immunolabeled receptors are found were identified as endosomes based on the presence of endocytic tracers (lucifer yellow and cationized ferritin). The lysosomal membrane marker, lgp120, was associated with a separate population of swollen vacuoles that did not contain detectable Man6P receptors. When cells were allowed to recover from weak base treatment, the receptors reappeared in the Golgi cisternae of most cells (approximately 90%) within approximately 20 min, indicating that as the intra-endosomal pH drops and lysosomal enzymes dissociate, the entire population of receptors rapidly recycles to Golgi cisternae. When NH4Cl-treated cells were allowed to endocytose Man6P, a competitive inhibitor of lysosomal enzyme binding, the receptors also recycled to the Golgi cisternae, suggesting that lysosomal enzymes can dissociate from the receptors under these conditions (high pH + presence of competitive inhibitor). From these results it can be concluded that the intracellular itinerary of the 215-kD Man6P receptor involves its cycling via coated vesicles between the Golgi complex and endosomes, ligand dissociation is both necessary and sufficient to trigger the recycling of Man6P receptors to the Golgi complex, and endosomes rather than secondary lysosomes represent the junction where endocytosed material and primary lysosomes carrying receptor-bound lysosomal enzymes meet.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mannose-6-phosphate receptors for lysosomal enzymes cycle between the Golgi complex and endosomes. 294 25

The brain is the most compartmentalized organ. It is also highly aerobic. Because nerve cells grow but do not regenerate, the brain is the organ best suited for the accumulation of metabolic errors colocalized in specific areas of the brain over an extended period. Alzheimer's disease (AD) is primarily a neurological disorder of the elderly. It is suggested that this disorder results from the accumulation of such errors, and that AD onset aluminum and iron contribute to but do not necessarily initiate the onset of the disease. In vitro and in vivo evidence summarized here suggests that this is effected by interfering in the utilization of glucose and glucose-6-phosphate, and sequestration of iron by ferritin. beta-amyloid precusor proteins (beta-APPs) are normal components of the human brain and some other tissues. Proteolysis of these, presumably by serine proteases, generates a 39 to 42 amino acid long peptide, the alpha-amyloid (beta-AP). In AD brains, beta-AP aggregates into plaque, the hallmark of AD brains. Some of the alpha-APPs also contain a 56 amino acid long segment which inhibits serine proteases. We show that in vitro, at pH 6.5, aluminum activates beta-chymotrypsin 2-fold and makes it dramatically resistant to protease inhibitors such as bovine pancreatic trypsin inhibitor (bPTI) or its mimic present in the beta-amyloid precursor proteins (beta-APPs). Iron and oxygen are reported to favor cross-linking of beta-AP in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron and aluminum homeostasis in neural disorders. 784 99

We previously demonstrated both mannose 6-phosphate receptor (MPR) and cathepsin L in early autophagic vacuoles of cultured rat fibroblasts. This suggested that the enzyme may originate either from the receptor-enriched prelysosomal compartment (PLC) or from the trans-Golgi network (TGN). In the present ultrastructural study, we elucidated the roles of the PLC and TGN in lysosomal enzyme delivery to autophagic vacuoles. Firstly, we studied whether endocytic markers, cationized ferritin (CF), bovine serum albumin-gold or horseradish peroxidase (HRP), can be detected in autophagic vacuoles. Autophagy was induced by serum removal from the medium with or without leupeptin, an inhibitor of cysteine proteinases. Endocytic markers were not detected in autophagic vacuoles after short uptake which filled the early endosome, but only after longer labeling which filled the PLC. The markers were usually found in advanced autophagic vacuoles containing partially degraded cytoplasm and complex internal membranes which are the characteristic of the PLC. HRP-positive vesicles were also observed in continuity with early autophagic vacuoles containing intact cytoplasm. After uptake and transport of CF and HRP to the PLC, these markers were delivered to autophagic vacuoles even if microtubules were disrupted in vinblastine before the induction of autophagy. Secondly, we studied whether MPRs transport cathepsin L to autophagic vacuoles directly from the TGN. Two inhibitors of MPR-mediated enzyme transport, tunicamycin and chloroquine, were used. Quantitative immunocytochemistry showed that neither of these drugs prevented cathepsin L delivery to autophagic vacuoles. The results suggest that a large proportion of lysosomal enzymes is delivered to autophagic vacuoles from the PLC by a microtubule-independent manner. The first enzymes may be transported in small PLC-derived vesicles or tubules which are reached by HRP but not by CF and gold. Later, the autophaged cytoplasm is delivered to larger vacuolar parts of the PLC. Mannose 6-phosphate receptors transport no or only trace amounts of lysosomal enzymes to autophagic vacuoles directly from the TGN.
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PMID:Autophagic vacuoles fuse with the prelysosomal compartment in cultured rat fibroblasts. 822 8