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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteoglycan alterations in the carotid arteries of normolipemic rabbits during the first 14 days after injury were evaluated by morphometric analysis of ruthenium red-stained sections using transmission electron microscopy and by incorporation of 35S-sulfate. Two types of de-endothelializing injury were compared, air-drying and balloon catheter. Three days after either injury, a transient increase in concentration of 35S-labeled glycosaminoglycans, changes in distribution of 35S-sulfate among glycosaminoglycans, and a two- to threefold increase in 35S-sulfate content (measured as 35S/micrograms glycosaminoglycan) were observed. Morphometric analysis revealed an alteration in medial proteoglycan distribution and morphology at 3 days after injury, which was more evident after air-drying than balloon injury. In response to either injury, metabolically activated smooth muscle cells were associated with very large proteoglycan granules (diameter: > 60 nm) which possibly contained glycosaminoglycans with longer chains and/or altered charge densities. By 14 days after either injury, the distribution of medial proteoglycan returned to normal and a neointima formed. The neointima was thicker following balloon injury, but irrespective of the nature of the injury proteoglycan concentration was higher in the re-endothelialized than in non-reendothelialized areas. The alterations in extracellular proteoglycan of the intima-medial layers induced by these two forms of injury may influence the pattern of wound healing but are not associated with lipid deposition within the time frame examined.
Exp Mol Pathol 1993 Apr
PMID:Transient morphological and biochemical alterations of arterial proteoglycan during early wound healing. 849 18

Human serum proteoglycans were isolated from random serum samples from healthy blood donors by cetylpyridinium chloride precipitation technique. Their concentration (14 +/- 6 mg/l +/- S.D.) corresponded to that of other mammals. Electrophoretic separation on polyacrylamide gel with a subsequent staining for glycans revealed four major bands from 175 to 80 kDa. Incubation in vitro with 0.1, 0.2 or 0.5 mM NiCl2 for 1 h caused a loss of glycan chains according to the nickel concentration. In the electrophoretic analysis, all proteoglycan bands diminished due to the incubation with the nickel salt. It seems that this approach could be used as a model for effects of chemicals on the proteoglycan metabolism.
Res Commun Mol Pathol Pharmacol 1995 Jun
PMID:Isolation and electrophoretic analysis of human serum proteoglycans and their reaction with nickel in vitro. 856 91

In this study we examined the production of proteoglycans by fibroblasts cultured from the left ventricular myocardium of normal adult rats. Various molecular species of proteoglycan were detected, either by labeling glycosaminoglycan chains with 35SO4 or by labeling the proteoglycan core protein with [35S]methionine. The medium of the cell cultures, which contained quantitatively most of the proteoglycans, appeared to consist mainly of biglycan, lesser amounts of decorin and proteoglycans of higher molecular weight. Biglycan and decorin were identified not only by the characteristic mobility of the intact protein and the core protein but also by immunolocation on Western blots. TGF-beta upregulated the synthesis of all these proteoglycans, coincident with elongation of glycosaminoglycan side chains observed for biglycan and decorin. The apparent molecular weight of the core protein of the two proteoglycans remained unaffected by TGF-beta. The results of these experiments suggest that with regard to proteoglycan synthesis and its regulation by TGF-beta, cultured fibroblasts originating from the myocardium share to a large extent the properties of cultured fibroblasts of other organs.
J Mol Cell Cardiol 1995 Oct
PMID:TGF-beta modulates the synthesis of proteoglycans by myocardial fibroblasts in culture. 857 35

In this study, the multiple factors that govern the unidirectional path of intraretinal axons, as well as the cellular movements prior to and during early axonogenesis, were investigated using time-lapse videomicroscopy. For several hours prior to overt axon elongation, young retinal ganglion cells send out transient minor processes in all directions at the pial surface. Time-lapse analysis of the chondroitin sulfate (CS)-containing matrix that has been suggested to play an important role in regulating this early differentiative event revealed the dynamic, wavelike properties of this extracellular matrix component. As the CS matrix dissipates across the immature ganglion cells, only one minor process, away from the highest concentration of CS peripherally and in the direction of the optic fissure centrally, is retained and becomes the mature axon. Focal concentrations of L1 appear at points of neurite contact with previously established axons, suggesting that this growth-promoting molecule is also involved with establishing the precise, unidirectional outgrowth pattern of retinal ganglion cell axons. NCAM was diffusely distributed on neural elements and on the neuroepithelial endfeet in the central and peripheral retina and, thus, may not be an essential unidirectional axon growth cue. Growth cones mechanically deflected 180 degrees from the optic fissure after the CS wave had receded from the central retina had morphologies and rates of elongation similar to those oriented in the proper direction. Growth cones deflected obliquely toward the ventral retinal periphery entered a territory of increasing CS-containing proteoglycan matrix and neurons with minor processes. As these deflected axons entered more deeply into this region they slowed down and sent out long transient branchlike processes. These observations illustrate the complex organization of the changing cell surface and matrix components within the retina during axonogenesis and axon outgrowth. The results also elucidate the potential importance of a cell state where immature neurons probe their environment via minor processes. These specialized neurites may provide the neuron with a way to sample a full 360 degrees of terrain around them. This method of exploring the environment could afford the cell a mechanism with which to sample, summate, and respond to physical structures as well as simultaneously occurring negative and positive molecular influences that are distributed unequally on either side of the cell body.
Mol Cell Neurosci 1995 Oct
PMID:Multiple factors govern intraretinal axon guidance: a time-lapse study. 858 13

Large aggregating chondroitin sulfate proteoglycan (CSPG/aggrecan) is one of the major extracellular matrix components in cartilage. The core protein is also large, over 200 kDa, and modular with a distinct correspondence between protein structural domains and the encoding exons. Here we report the isolation, using chick CSPG cDNA probes and the ensuing sequencing, of genomic clones containing exons encoding the chick CSPG core protein. The 5' two globular domains, G1 and G2, are encoded by four and three exons, respectively, and the interglobular domain is encoded by a single exon. The chondroitin sulfate attachment domain is encoded by the largest exon, 3,216 bp, which is approximately 50% of the total coding sequence. Combined with the previous report (Tanaka, T., Har-el, R. Tanzer, M.L. 1988 J. Biol. Chem. 263, 15831-15835), these data reveal that the chick CSPG gene contains at least 18 exons spanning a genome which is greater than 30 kb. No evidence was obtained for multiple genes for aggrecan in the chick genome. Elucidation of the chick genomic structure allows comparison of the avian and mammalian link protein genes to the homologous portions of avian and mammalian core protein genes (hyaluronate binding domain) with respect to their origins and paths of duplication and divergence.
J Mol Evol 1995 Dec
PMID:Gene structure of chick cartilage chondroitin sulfate proteoglycan (aggrecan) core protein. 858 32

NG2 is a chondroitin sulfate proteoglycan that is expressed on dividing progenitor cells of several lineages including glia, muscle, and cartilage. It is an integral membrane proteoglycan with a core glycoprotein of 300 kDa. In the present study we have characterized three molecular forms of the NG2 core protein expressed by different cell lines. Many cell lines that express the full length 300-kDa NG2 core protein also release a 290-kDa form into the medium. This species lacks the cytoplasmic domain but contains almost the entire ectodomain. Two core protein species, the intact 300-kDa form and a truncated 275-kDa form, are expressed at the surface of an NG2-transfected cell line U251NG52. The 275-kDa species lacks the cytoplasmic domain and at least 64 amino acids of the ectodomain. Mild trypsinization of B49 cells also generates the 275-kDa species, suggesting that this component is produced by proteolysis of the 300-kDa form. Conversion of the 300-kDa species to the 275-kDa form in U251NG52 cells is stimulated by reagents such as phorbol esters, which activate protein kinase C. Phorbol esters are also known to induce expression of metalloproteinases such as collagenase and stromelysin, which could be responsible for cleavage of the 300-kDa core protein. Although B49 cells do not spontaneously produce the truncated 275-kDa species, use of monoclonal antibodies against NG2 to block the interaction between NG2 and type VI collagen results in the appearance of the 275-kDa component in these cells. Thus the interaction between NG2 and type VI collagen, which contains a Kunitz-type proteinase inhibitor sequence in the alpha 3 chain, may protect the proteoglycan against proteolysis. This is consistent with the observed deficiency of U251NG52 cells in anchoring type VI collagen at the surface.
Mol Biol Cell 1995 Dec
PMID:Generation of truncated forms of the NG2 proteoglycan by cell surface proteolysis. 859 Aug 8

Proteoglycans and glycosaminoglycans in the aortic intima of diabetic rabbits and age-matched controls were examined at 2 weeks and 3, 6, and 12 months after alloxan (or saline) treatment. Measurements were made by morphometric analysis of ruthenium red-stained large proteoglycan granules (LPG) in electron micrographs and by analysis of 35S-labeled glycosaminoglycans, extracted and purified from the intima-media of aortas of rabbits which had been injected with 35S-sulfate 18 hr before exsanguination. There was a progressive increase in the area of the aortic intima with time which was greater in diabetic than in control rabbits. The concentration of proteoglycan (LPG/microns 2) and the concentration of the 35S-glycosaminoglycans in diabetic intima-media were similar to respective values of control intima-media throughout the 12 months. However, the specific radioactivity of the [35S]glycosaminoglycan pool from intima-media of diabetic rabbits was significantly less than that from controls (P < 0.001) at 6 and 12 months. In addition, the staining intensity of LPG of the diabetic compared to control extracellular matrix was decreased at these times. The profile and electrophoretic mobility of the glycosaminoglycan types were similar in diabetic and control intima-media. We conclude that the onset of diabetes in the rabbit has altered the metabolic turnover but not the concentration, sulfate content or profile of aortic intima-media proteoglycan and glycosaminoglycans.
Exp Mol Pathol 1995 Jun
PMID:Proteoglycan alterations in the aortic intima-media of alloxan-diabetic rabbits: an ultrastructural and biochemical study. 861 18

Lysosomal enzymes and IGF-II both bind to the mannose 6-phosphate (M6P)/IGF-II receptor. This receptor targets newly synthesized lysosomal enzymes to lysosomes. The functional meaning of IGF-II binding to this receptor is not well known. We have postulated that IGF-II, the Ser29 IGF-II variant (vIGF-II) and IGF-I on lysosomal cathepsin B and L activities from post-natal rabbit chondrocytes in vitro. This effect was compared with the ability of each peptide to stimulate chondrocyte-sulfated proteoglycan synthesis. The sulfating dose-response relationship of the IGF peptides corresponded to their relative binding affinities for the type I-IGF receptor (IGF-I > IGF-II > vIGF-II). The intracellular cathepsin B and L activities were inhibited in a time- and dose-dependent manner by IGF-II or vIGF-II. Maximal inhibition of cathepsin B and L activities (40 and 30% below controls, respectively) was found after an 8 h treatment with 100 ng/ml IGF-II or vIGF-II. By contrast, IGF-I up to 1 micrograms/ml or insulin up to 2 micrograms/ml had no inhibitory effect. The relative potency pattern corresponded to the binding profile of each ligand for the M6P/IGF-II receptor. A treatment of chondrocytes with IGF-I or insulin transiently increased the binding of radiolabelled IGF-II at the cell surface to approximately 120% of controls, whereas IGF-II or vIGF-II had no effect. Thus, it is unlikely that the inhibition of lysosomal enzyme activities by IGF-II peptides could result from a redistribution of M6P/IGF-II receptors from intracellular compartments to the plasma membrane. We hypothesize that internalized IGF-II peptides could occupy the intracellular M6P/IGF-II binding sites required for targeting of cathepsins B and L to lysosomes.
Mol Cell Endocrinol 1995 Sep 22
PMID:Inhibition of chondrocyte cathepsin B and L activities by insulin-like growth factor-II (IGF-II) and its Ser29 variant in vitro: possible role of the mannose 6-phosphate/IGF-II receptor. 867 28

In anchorage-dependent (AD) cultures of the outer cell population (OCP) from neonatal rat calvaria, transforming growth factor-beta 1 (TGF-beta) specifically upregulated the synthesis of chondroitin sulfate (CS) proteoglycan (PG) and uncoupled the inhibitory effect of increasing cell density on CS PG synthesis (reference #30). Utilizing the same cell population, we have further examined the possibility that glycosaminoglycans (GAG) known to be synthesized and secreted by bone cells might exert feedback effects on GAG synthesis and/or its stimulation by TGF-beta. Although addition of TGF-beta alone stimulated net synthesis of HA and CS in both AD and anchorage-independent (AI) cultures, significant alterations of basal and TGF-beta-stimulated GAG synthesis by exogenous GAGs were observed only in AI cultures. In AI cultures exogenously added hyaluronic acid (HA) markedly enhanced the basal synthesis of HA and CS while heparin (H) suppressed the basal synthesis of HA, CS as well as dermatan sulfate (DS). Also, the addition of HA markedly potentiated the stimulation by TGF-beta of HA and CS synthesis as did heparan sulfate (HS) for CS and DS synthesis. H suppressed the stimulation of the synthesis of HA, CS and DS by TGF-beta. Overall, our results indicate specific effects of individual GAGs on basal and TGF-beta-stimulated GAG synthesis in OCP cultures. We suggest that some of the GAGs in the OCP microenvironment (which with the exception of HA are covalently linked to protein cores of secreted PGs), acting in concert with TGF-beta, may serve as an amplification system for upregulating GAG synthesis in the rapidly growing neonatal calvarium.
Mol Cell Biochem 1996 May 10
PMID:Exogenous glycosaminoglycans (GAG) differentially modulate GAG synthesis by anchorage-independent cultures of the outer cells from neonatal rat calvaria in the absence and presence of TGF-beta. 879 Dec 81

The receptor protein tyrosine phosphatase (RPTP) zeta/beta and a major isoform, phosphacan, a chondroitin sulfate proteoglycan that contains the RPTP zeta/beta extracellular domain but not the transmembrane and intracellular phosphatase domains, are expressed abundantly in the nervous system, primarily by astroglia. Because of similarities in the expression patterns of RPTP zeta/beta and the receptor tyrosine kinase TrkB, we investigated whether RNAs encoding these proteins were co-localized during development, which would suggest that these molecules might functionally interact in vivo. By in-situ hybridization, we noted extensive areas of overlap in the expression of trkB and RPTP zeta/beta mRNAs in the developing peripheral and central nervous systems. Analysis with a probe specific for the catalytic TrkB isoform suggested that RPTP zeta/beta and non-catalytic trkB mRNAs were co-expressed in particular regions of the nervous system while the catalytic trkB and RPTP zeta/beta transcripts were also, but to a lesser extent. RPTP zeta/beta and phosphacan expression were extremely similar, differing particularly in the level of expression in the ventricular and subventricular zones, hippocampus, and ependyma. Furthermore, both RPTP zeta/beta and phosphacan mRNAs were found in several subsets of neurons as well as astrocytes. Following CNS injury, we observed robust induction of RPTP zeta/beta mRNA in areas of axonal sprouting, and of both RPTP zeta/beta and phosphacan mRNAs in areas of glial scarring, implying that the encoded proteins and the cell adhesion molecules and extracellular matrix proteins to which they bind may contribute to recovery from injury and perhaps regulation of axonal regrowth in the nervous system.
Brain Res Mol Brain Res 1996 Aug
PMID:Comparison of RPTP zeta/beta, phosphacan, and trkB mRNA expression in the developing and adult rat nervous system and induction of RPTP zeta/beta and phosphacan mRNA following brain injury. 884 16


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