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Query: UNIPROT:P06889 (Mol)
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Lapine articular chondrocytes in vitro were used to study the effects of Fe3+, Fe2+, ferritin and haemoglobin on cell proliferation, synthesis of proteoglycans and morphological structure. Fe3+ (10, 100 and 500 micrograms/ml) reduced the DNA content of cultures by approximately 35% as well as inhibiting proteoglycan synthesis. Chondrocytes showed positive cytoplasmic staining for both ferric and ferrous ions at the 500 micrograms/ml concentration. Fe2+ (100 micrograms/ml) also decreased DNA content and proteoglycan synthesis, although no iron uptake by the chondrocytes could be detected. Ferritin (1.0, 0.5 and 0.1 micrograms/ml) elicited a significant inhibition of proteoglycan synthesis without affecting cellular DNA synthesis. 1 and 5 micrograms/ml of haemoglobin each reduced the DNA content of cultures by 60%, whilst markedly inhibiting proteoglycan synthesis (75 and 99% respectively). None of the substances tested caused chondrocyte toxicity. The ability of Fe3+, Fe2+, ferritin and, in particular, haemoglobin to inhibit chondrocyte proteoglycan synthesis may represent a pathway whereby cartilage is susceptible to destruction in the haemophilic joint.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Alterations in chondrocyte morphology, proliferation and binding of 35SO4 due to Fe(III), Fe(II), ferritin and haemoglobin in vitro. 612 12

Stage 21 to 22 chicken embryo limb bud cells were infected with a temperature-sensitive mutant of Rous sarcoma virus and were grown in culture. Although control, uninfected cells yielded definitive chondroblasts (by day 4) which initiated the synthesis of the cartilage-characteristic proteoglycan, the transformed cells grown at the permissive temperature failed to do so. These effects were fully reversible after a shift to the nonpermissive temperature. In addition, infected cells at the nonpermissive temperature expressed traits of terminal chondrogenic maturation 2 to 3 days earlier than parallel, uninfected cells. Thus, Rous sarcoma virus-induced transformation reversibly blocks terminal limb bud cell chondrogenesis in culture, at the nonpermissive temperature, viral infection may also induce intracellular or extracellular conditions which favor or accelerate the process of chondrogenic cell maturation.
Mol Cell Biol 1983 Aug
PMID:Infection of chick limb bud presumptive chondroblasts by a temperature-sensitive mutant of Rous sarcoma virus and the reversible inhibition of their terminal differentiation in culture. 631 95

Analysis of the X-ray diffraction pattern from an oriented, polycrystalline fiber of a potassium chondroitin 4-sulfate proteoglycan shows that the polysaccharide chains have a left-handed 3-fold helical secondary structure stabilized by intra- and intermolecular hydrogen bonds. Two antiparallel chains pass through each trigonal unit cell, which has dimensions a = b = 1.385 nm, c = 2.776 nm and space group symmetry P3(2)21. The cations and water molecules in the crystals are not all periodic and only one potassium ion and four water molecules per disaccharide were located by difference Fourier methods. Sodium chondroitin 4-sulfate forms an analogous structure with polyanions of similar geometry. However, the packing arrangements in the two salts are quite different, presumably because of the different co-ordination preference of K+ and Na+. Thus the relatively small differences between these two cations are greatly amplified by the idiosyncratic polymer networks they promote.
J Mol Biol 1983 Oct 05
PMID:Chondroitin 4-sulfate: comparison of the structures of the potassium and sodium salts. 641 88

We report here the existence of a crystalline molecular packing of type II collagen in the fibrils of the lamprey notochord sheath. This is the first finding of a crystalline structure in any collagen other than type I. The lamprey notochord sheath has a composition similar to that of cartilage, with type II collagen, a minor collagen component with 1 alpha, 2 alpha and 3 alpha chains, and cartilage-like proteoglycan. The high degree of orientation of fibrils in the notochord makes it possible to use X-ray diffraction to determine collagen fibril organization in this type II-containing tissue. The low angle equatorial scattering shows the fibrils are all about 17 nm in diameter and have an average center-to-center separation of 31 nm. These results are supported by electron microscope observations. A set of broad equatorial diffraction maxima at higher angles represents the sampling of the collagen molecular transform by a limited crystalline lattice, extending over a lateral dimension close to the diameter of one fibril. This indicates that each 17 nm fibril contains a crystalline array of molecules and, although a unit cell is difficult to determine because of the broad overlapping reflections, it is clear that the quasi-hexagonal triclinic unit cell of type I collagen in rat tail tendon is not consistent with the data. The meridional diffraction pattern showed 26 orders with the characteristic 67 nm periodicity found for tendon. However, the intensities of these reflections differ markedly from those found for tendon and cannot be explained by an unmodified gap/overlap model within each 67 nm period. Both X-ray diffraction and electron microscope data indicate a low degree of contrast along the fibril axis and are consistent with a periodic binding of a non-collagenous component in such a way as to obscure the gap region.
J Mol Biol 1984 Jun 25
PMID:Crystalline fibril structure of type II collagen in lamprey notochord sheath. 674 78

Perlecan is a modular heparan sulfate proteoglycan that harbors five domains with homology to the low density lipoprotein receptor, epidermal growth factor, laminin and neural cell adhesion molecule. Using a monoclonal antibody directed against the laminin-like domain of perlecan, we have recently shown that perlecan is widely expressed in all lymphoreticular systems. To investigate further this observation we have studied the expression of perlecan in two human leukemic cell lines. Using reverse transcriptase-PCR, ribonuclease protection assay, and metabolic labeling we detected significant perlecan expression in the multipotential cell line K562, originally derived from a patient with chronic myelogenous leukemia. In contrast, the promyelocytic cell line HL-60 expressed perlecan at barely detectable levels. These results were intriguing because the K562 cells do not assemble or produce a classical basement membrane. Following induction with either sodium butyrate or the phorbol diester 12-0-tetradecanoylphorbol-13-acetate (TPA), K562 and HL-60 differentiate into early progenitor cells with erythroid or megakaryocytic properties, respectively. Following treatment of K562 and HL-60 cells with either of these agents, perlecan expression was markedly increased in K562 cells. In contrast, we could detect perlecan protein synthesis in HL-60 cells only at very low levels, even after induction with TPA or sodium butyrate. Collectively, these results indicate that perlecan is actively synthesized by bone marrow derived cells and suggest that this proteoglycan may play a role in hematopoietic cell differentiation.
Mol Cell Biochem 1995 Apr 12
PMID:The proteoglycan perlecan is expressed in the erythroleukemia cell line K562 and is upregulated by sodium butyrate and phorbol ester. 754 67

Specific changes in composition and content of lung extracellular matrix (ECM) proteoglycans (PGs) and hyaluronan (HA) have been observed during the acute response to damage in several forms of injury including infant respiratory distress syndrome (IRDS). These ECM components are thought to modulate the healing response. Hyperoxia, a contributing factor to IRDS, is known to damage both adult and developing lung, however, the extent and pattern of impairment depends on lung maturity. We hypothesized that exposing neonatal rats to hyperoxia alone might result in changes in lung HA, as well as in age-specific changes in lung PGs, similar to those shown to occur in IRDS. In control rats, lung HA decreased over the first 10 days of life, whereas rats exposed to hyperoxia exhibited a time-dependent, time-limited increase in both lung HA and lung wet weight. Histochemistry showed the HA in hyperoxia-exposed lungs to be accumulated in perivascular cuffs of medium sized arteries, and in the alveolar walls. Rats were then exposed to normoxia or hyperoxia for 7 days beginning at either 3 days of life (neonatal) or 21 days (adolescent), and lung tissue was cultured in the presence of [35S]-sulfate to label newly synthesized PGs. Proteoglycans were extracted, and analyzed by isopycnic CsCl gradient centrifugation, sequential enzymatic deglycosylation, size chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). When controlled for total protein extracted, 63% more label was incorporated into large molecular weight material in the tissue exposed to hyperoxia, with a 95% increase in incorporation in the most dense fraction, D1. [35S]-Sulfate incorporation into chondroitin and dermatan sulfate in hyperoxic tissue specifically increased 116% (242% in the D1 fraction), while incorporation into heparan sulfate remained essentially unchanged. There was a nearly fivefold increase in [35S]-sulfate incorporation into chondroitin sulfate chains in the D1 fraction. When the D1 fractions of extracts of treated and control rat lungs were compared on SDS-PAGE, a large chondroitin sulfate proteoglycan (CSPG; core protein of 195 kDa) was upregulated in the D1 fraction from hyperoxic tissue of neonatal rats, but was not detected in the lungs of adolescent animals exposed to hyperoxia. This CSPG and four additional large CSPGs were noted to be upregulated on western blotting by a polyclonal antibody directed against the G1 domain of the aggrecan protein core. We conclude that hyperoxia alone causes an increase in lung HA and lung water, and speculate that this contributes significantly to the clinical syndrome of IRDS. In addition, several large CSPGs are upregulated by hyperoxic exposure in a developmentally specific manner. We speculate that this increase in CSPGs may interfere with the normal developmental sequence of events, contributing to hypoalveolarization.
Am J Respir Cell Mol Biol 1995 Dec
PMID:Hyperoxia alone causes changes in lung proteoglycans and hyaluronan in neonatal rat pups. 757

Eight syngeneic rat monoclonal antibodies that recognize structurally overlapping epitopes on the chondroitin proteoglycan NG2, a tumour-specific antigen on the chemically induced rat chondrosarcoma HSN, have been analysed for the sequence of their immunoglobulin heavy (H) and light (L) chain variable (V) regions. This analysis defined five groups of antibodies which are very similar for both the H and L chains and revealed that a wide range of different V regions are capable of binding to the same antigenic determinant. However, three mAbs, 11/160, ALN/12/17 and ALN/9/94, which recognize a sequential epitope, were found to use almost identical heavy (V-D-J) and light (V-J) chains in regions demonstrating an exclusivity in specific protein-protein interaction for this particular epitope. Two other mAbs, ALN/11/53 and AL/3/12, used similar V and J segments but totally different D regions. With the exception of the pair ALN/11/53 and AL/3/12, this grouping of antibodies matches that derived from the idiotypic specificity study we have reported previously. The reactivity pattern of Ab1 11/160, ALN/12/17 and ALN/9/94 with six anti-idiotopic mAbs raised against 11/160 demonstrated that the idiotope recognized by Ab2 HIM/3/41 was defined by a single amino acid, Asn, at position 52 within the CDR2 loop of the VH region; whereas the D region of Ab1 ALN/11/53 was implicated as the structural correlate of idiotypy. The substitution of AsnH52 influenced the Id recognition but Ag binding was not affected suggesting that Ab2 HIM/3/41 did not mimic the NG2 Ag.
Mol Immunol 1995 Jul
PMID:Primary structure of the variable regions encoding antibody to NG2, a tumour-specific antigen on the rat chondrosarcoma HSN. Correlation of idiotypic specificities with amino acid sequences. 765 96

Reproducible effects of growth hormone (GH) on primary isolated cells in monolayer are highly dependent on the culture conditions and/or the fraction of GH responsive cells. To study the effect of GH at the cellular level, a homogenous cell line with both GH responsiveness and chondrogenic properties was established. Primary isolated cells from 18-day-old fetal rat tibia were subcultured using a strict protocol for passages (every third day and a seeding density of 15,000/cm2). Of six established cell lines, one fetal tibia cell line No. 5 (FTC 5) expressed adipogenic and chondrogenic properties at a low frequency. Cells from FTC 5 were subcultured in soft agar suspension with the addition of bovine GH (100 ng/ml). After 14 days in culture eight monoclonal cell lines were established from individual large colonies. Two subclones, FTC 5:3 and FTC 5:6, expressed a chondrogenic phenotype as demonstrated by chondrocyte foci, alcian blue staining and production of type II collagen. Further characterization of FTC 5:3 revealed specific binding of bovine GH with an affinity of 1.7 x 10(9) M-1, and approximately 7300 receptors/cell. Northern blot analysis of FTC 5:3 with a 32P-labeled RNA probe complementary to an extracellular part of the rat GH receptor, revealed two major labeled bands (4.0 and 1.2 kilobases). Both GH and insulin-like growth factor-I (IGF-I) stimulated 3H-thymidine uptake in FTC 5:3 (194 +/- 28% and 405 +/- 127% over control, respectively), while proteoglycan synthesis, as measured by [35S]sulphate uptake, was stimulated by IGF-I only (101 +/- 18% over control).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Feb
PMID:Establishment of a growth hormone responsive chondrogenic cell line from fetal rat tibia. 768 19

Madin-Darby canine kidney (MDCK) cells and Chinese hamster ovary (CHO) cells were transfected with wild-type and cytoplasmic deletion mutants of mouse syndecan-1 to study the requirements for transport and polarized expression of this proteoglycan. Expression in MDCK cells revealed that wild-type syndecan-1 is directed to the basolateral surface via a brefeldin A-insensitive route. A deletion of the last 12 amino acids of the syndecan-1 cytoplasmic tail (CT22) was sufficient to result in the appearance of mutant proteoglycans at both the basolateral and apical cell surfaces. Treatment with brefeldin A was able to prevent apical transport of the mutants. We thus propose that the C-terminal part of the cytoplasmic tail is required for steady-state basolateral distribution of syndecan-1. In CHO cells a deletion of the last 25 or 33 amino acids of the 34-residue cytoplasmic domain (CT9 and CT1, respectively) resulted in partial retention of the mutants in the endoplasmic reticulum (ER). A deletion mutant lacking the last 12 amino acids (CT22) was not retained. Interestingly, the unglycosylated core proteins of the CT9 and CT1 mutants showed a significantly lower apparent molecular weight when analyzed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis than wild-type syndecan-1. However, when CHO transfectants expressing the CT1 mutant were incubated with brefeldin A, causing fusion of the ER and Golgi, CT1 ran with an almost equally high apparent molecular weight as the wild-type molecule. This would suggest that syndecan-1 undergoes extensive posttranslational modifications or forms an SDS-resistant dimer/complex after transit from the ER.
Mol Biol Cell 1994 Dec
PMID:Analysis of transport and targeting of syndecan-1: effect of cytoplasmic tail deletions. 769 13

Atrial myocardial cells store atrial natriuretic factor and secrete the peptide in response to extracellular stimulation. Ventricular myocardial cells also exhibit stimulated secretion of atrial natriuretic factor but with little or no intracellular storage. The stimulated secretion of other proteins from these cells is poorly characterized. In the present study the secretion of sulfated macromolecules from Na2(35)SO4 labeled atrial and ventricular myocardial cells was quantitated. Both cell types secreted a chondroitin sulfate proteoglycan, as evidenced by glycanase digestion. Endothelin-1, a known stimulator of ANF secretion, stimulated secretion from atrial cells about 70% but had no effect on ventricular cell secretion. The differential stimulation of atrial and ventricular cell secretion was not due to the absence of a regulated secretory pathway in the latter cell type since phorbol ester stimulated secretion from both cell types. This result indicates that differences exist in the early steps of signal transduction between atrial and ventricular cells. Pancreastatin, a regulatory peptide derived from chromogranin A, stimulated atrial cell secretion 90%. This result suggests that chromogranin A, which has been identified in atrial secretory granules, may play an autoregulatory role in atrial secretion.
J Mol Cell Cardiol 1995 Feb
PMID:Pancreastatin stimulates secretion from neonatal rat atrial cells. 777 82


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