Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serine residues, which are the sites of phosphorylation in proteoglycans, were demonstrated to be located on chondroitin sulfate-containing peptides. These peptides appeared to be derived primarily from the chondroitin sulfate-rich region of the proteoglycan core protein. The localization of phosphate moieties in the chondroitin sulfate-containing peptides was observed in all experiments. The phosphate moieties were retained on chondroitin sulfate-containing peptides after the protein core was treated with either papain or trypsin. Two phosphopeptide preparations, derived from chondroitin sulfate-containing peptides of proteoglycan subunits, were extensively purified. These 2 phosphopeptide preparations were shown by carbohydrate analysis to be free of keratan sulfate-containing peptides or peptides from the hyaluronic acid binding region of the core protein. One of the phosphopeptide preparations had a phosphate: serine molar ratio of 0.40. This indicated that nearly one-half of the serine residues were phosphorylated rather than glycosylated. Peptides derived from the core protein that contained keratan sulfate had no phosphate moieties.
Arthritis Rheum 1985 Jul
PMID:Phosphorylation of proteoglycans. Identification of phosphorylation sites in chondroitin sulfate-rich region of core protein. 392 58

Using enzyme-linked immunosorbent assays and radioimmunoassays employing chondroitinase ABC-treated rabbit cartilage proteoglycan, we have shown that approximately one-third of the outbred New Zealand white rabbits we have examined possess naturally occurring antibodies which react with oligosaccharides of hyaluronic acid (independently of chain length) bearing saturated and 4,5-unsaturated glucuronosyl residues at the nonreducing ends. Such antibodies were also found in a similar proportion of rabbits with an experimental inflammatory arthritis. There was a preferential reactions in the majority of sera with unsaturated oligosaccharides of hyaluronic acid. One serum (R64) reacted only with unsaturated oligosaccharides of hyaluronic acid. Sera reacted also with unsaturated (never saturated) oligosaccharides of chondroitin 4-sulfate and with chondroitin 6-sulfate, particularly when chondroitin sulfate oligosaccharides remained bound to a proteoglycan core protein. Reactions were also observed to both unsaturated and saturated oligosaccharides of chondroitin. Some of these sera also reacted with intact hyaluronic acid and chondroitin but never with intact chondroitin sulfate. The antibodies were present in the IgG fraction of four sera studied and in the IgM fraction of one of these sera: they bound through the F(ab')2 region of the molecule. These observations suggest that, in some rabbits, humoral immunity to hyaluronic acid and/or chondroitin sulfate bound to core protein can develop after these reactive glycosaminoglycans have been degraded by eliminases or hydrolases produced by naturally occurring bacteria and rabbit cells, respectively. Immunological studies of proteoglycans and hyaluronic acid treated with eliminases and hydrolases employing rabbit antisera, and possibly those from other species, should be evaluated in the light of these observations.
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PMID:Rabbit antibodies to degraded and intact glycosaminoglycans which are naturally occurring and present in arthritic rabbits. 399 11

Rabbits were immunized with purified caprine arthritis-encephalitis virus and examined for neutralizing activity. Analysis of virus-antiserum interaction at 37 degrees C demonstrated little loss of viral infectivity after incubation with heat-inactivated rabbit antiserum for 60 min. However, sensitization of virus (as assessed by the addition of complement) occurred almost immediately and was 95% complete after 10 min. The complement-dependent neutralizing activity was associated with the immunoglobulin G fraction of rabbit antiserum. Addition of goat anti-rabbit immunoglobulin G to the immune rabbit serum-caprine arthritis-encephalitis virus mixture also resulted in neutralization of infectivity when unbound antibody was removed before addition of the anti-immunoglobulin. Serum from most caprine arthritis-encephalitis virus-infected goats contains antibody activity to the core protein p28, as demonstrated by immunodiffusion and enzyme-linked immunosorbent assay. However, attempts to demonstrate neutralizing activity in the serum of goats up to 1.5 years post-inoculation or in serum of hyperimmunized goats were unsuccessful when the sera were examined alone or in combination with complement or rabbit anti-goat immunoglobulin or both.
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PMID:Neutralizing antibody response of rabbits and goats to caprine arthritis-encephalitis virus. 629 2

Purified proteoglycan subunits from human articular, bovine articular and nasal cartilages, and a rat chondrosarcoma were phosphorylated in vitro by beef heart cAMP-dependent protein kinase in the presence of gamma 32P-ATP. In these experiments, a maximum of 1.7 moles of 32P were incorporated per mole of proteoglycan from human cartilage. Phosphorylation was dependent on the presence of cAMP. Analysis by autoradiography revealed that serine residues in the core protein of the proteoglycan were the sites of phosphorylation. Treatment of proteoglycan subunits with chondroitinase ABC and alkaline phosphatase prior to reaction with cAMP-dependent protein kinase increased the incorporation of 32P by 12-30% when compared with untreated proteoglycans. These data indicate that proteoglycans in cartilage can be phosphorylated by cAMP-dependent protein kinase.
Arthritis Rheum 1984 Sep
PMID:Phosphorylation of proteoglycans from human articular cartilage by a cAMP-dependent protein kinase. 647 53

Four normal (NF) and 4 scleroderma skin fibroblast (SF) strains were compared with respect to 1) basal 14C-glucosamine and 35SO4-labeled glycosaminoglycan (GAG) synthesis, 2) responsiveness to autacoid mediators, and 3) performance following maximal stimulation. Under basal conditions, SF synthesized and secreted 2-3 times more radioactive hyaluronic acid than the NF (P less than 0.001); molecular volume by gel chromatography was similar and suggested a high molecular weight product. SF were essentially as responsive to normal lymphoid and platelet factors as were NF. No consistent qualitative or quantitative differences in sulfated GAG synthesis were noted between the 2 groups of cells. Incubation of NF and SF with a false "core protein" such as p-nitrophenyl-beta-D-xyloside suggested that synthesis of the core protein was rate limiting; SF and NF were equally facile in SO4-GAG chain synthesis in the presence of a beta-xyloside. SF appear to retain in vitro a partially activated state for many generations, at least with respect to hyaluronic acid synthesis.
Arthritis Rheum 1983 Nov
PMID:Connective tissue activation. XXVII. The behavior of skin fibroblasts from patients with scleroderma. 663 95

Previous studies have shown that sulfated proteoglycans from human articular and epiphyseal cartilage were phosphorylated. These macromolecules contribute to the stiffness and resiliency of this tissue. We demonstrate here that the phosphate moieties are an integral part of proteoglycan subunits. Specifically, evidence is presented which indicates that proteoglycan monomers contain 3 to 4 phosphate moieties per core protein and that these appear to exist as phosphoserine residues. Furthermore, the data illustrate that human articular cartilage also contains more than 20 different phosphoproteins, some of which are closely associated with proteoglycan aggregates. Proteoglycan subunits were purified from extracts of articular cartilage or from media fractions which had been used to label tissue specimens with 32P-orthophosphate. Chemical and radiographic analyses revealed that the phosphate concentration with respect to sulfate and uronic acid content remained constant when purified proteoglycan monomers were subjected to equilibrium ultracentrifugation and size-exclusion chromatography. That the phosphate moieties were bound to proteoglycan monomers via monoester linkages was indicated by the release of 32P-orthophosphate from proteoglycan subunits incubated under mild alkaline conditions or reacted with acid or alkaline phosphatases. Identification of serine residues in the core protein as the sites of phosphorylation was made by autoradiography of thin layer plates on which hydrolyzed samples of purified 32P-proteoglycan subunits had been subjected to 2-dimensional electrophoresis/chromatography. Quantification of 3 to 4 phosphate moieties per core protein of 200,000 daltons was made by chemical analysis of inorganic phosphate released from proteoglycans by acid hydrolysis.
Arthritis Rheum 1984 Jan
PMID:Phosphorylation of proteoglycans from human articular cartilage. 669 60

Proteoglycan alterations were studied in articular cartilage obtained from control and antigen induced arthritis of the rabbits. Agarose/polyacrylamide-gel electrophoretic patterns of proteoglycan revealed heterogeneity in each experiment. In the cartilage of the antigen induced arthritis the following changes were demonstrated at the early stage; 1) an increase in the non-aggregated proteoglycan content, 2) a decrease in the size of the proteoglycan, 3) a decrease in the ability to interact with hyaluronic acid, 4) a constancy in the length of the glycosaminoglycan chains, 5) a decrease in hexuronate/protein, galactosamine/glucosamine and galactosamine/amino acid ratio, and 6) a decrease in serine and threonine content of the core protein. At the late stage the following changes were most pronounced; 1) a recovery in the size of the proteoglycan, 2) a marked decrease in the ability to interact with hyaluronic acid, 3) an increase in galactosamine/glucosamine and a gradual decrease in glucosamine/amino acid ratio, and 4) an increase in serine and glycine and a decrease in half cysteine and methionine content of the core protein. The results indicate that the smaller size of the proteoglycan from articular cartilage was due to degradation of the core protein at the early stage. But there seems to be some changes of proteoglycan synthesis at the late stage.
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PMID:[Studies on the biochemical alterations of cartilage proteoglycan in antigen induced arthritis of rabbit (author's transl)]. 679 34

In this study, virtually all sulfated glycosaminoglycan (GAG) synthesized and secreted by human synovial cells, both normal and rheumatoid, was detected in the form of proteoglycans of monomeric size. Enzyme hydrolysis studies that were performed demonstrated dermatan sulfate to be the dominant GAG in the proteoglycan, with lesser amounts of chondroitin 4/6 sulfate. Exposure to beta-xyloside, used as a false "core protein," resulted in marked enhancement of GAG chain formation, suggesting that the synthesis of the sulfated carbohydrate chain itself was not rate limiting. Proteoglycan synthesis and secretion were stimulated by several types of connective tissue activating peptides (CTAP); CTAP-III stimulation of incremental core protein and glycosaminoglycan was shown to be of a similar magnitude. Since chain synthesis was not rate limiting, it is suggested that stimulated proteoglycan formation caused by the CTAP peptides may be primarily modulated through increased formation of core protein.
Arthritis Rheum 1983 Apr
PMID:Connective tissue activation. XXV. Regulation of proteoglycan synthesis in human synovial cells. 683 74

The effect of aspirin on the degeneration of knee cartilage caused by immobilization was examined. If dogs were fed aspirin daily (serum salicylate = 20-25 mg/dl) for 6 weeks while one hind limb was immobilized in a cast, the decreases in uronic acid content and net proteoglycan synthesis in cartilage from the immobilized knee were significantly greater than the decreases in cartilage from immobilized knees of dogs that had not received aspirin (P less than 0.01). Furthermore, neither aspirin administration nor immobilization alone affected the extractability of proteoglycans from the cartilage. However, in organ cultures of cartilage from the immobilized knee of dogs fed aspirin, the proportion of the total 35S-proteoglycans present in the culture medium was nearly twice that from cultures of cartilage of the contralateral knee. Also, more than twice as many of the total tissue proteoglycans (uronic acid) were extractable with 0.4 M guanidinium chloride, a nondissociating solvent (P less than 0.01). Regardless of whether the dogs received aspirin, the in vitro interaction of proteoglycans with hyaluronic acid from cartilage of the immobilized knee was diminished, apparently due to an abnormality in the hyaluronate-binding region of the core protein. Although these results indicate that aspirin had an adverse effect in vivo on articular cartilage of immobilized joint, aspirin administration did not preclude reversal of all of the above changes if the dog was allowed to walk about in a pen for 3 weeks after cast removal. If, however, the dog was run daily on a treadmill for 3 weeks after cast removal, the decrease in uronic acid content in cartilage from the immobilized knee persisted and was more profound if the animal had received aspirin than if it had not (P less than 0.01).
Arthritis Rheum 1982 Nov
PMID:Aspirin aggravates the degeneration of canine joint cartilage caused by immobilization. 713 4

Immunization of BALB/c mice with chondroitin sulfate-depleted proteoglycan (aggrecan) of fetal human cartilage produces progressive polyarthritis and ankylosing spondylitis. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immune responses against the host mouse cartilage proteoglycan (PG). Although cartilage PGs from various species have many biochemical and immunological similarities, only a select group of PGs from fetal and newborn human, fetal pig and canine articular cartilages, human osteophytes and human chondrosarcomas are able to induce arthritis in BALB/c mice. Arthritis develops only in mice that also develop autoantibodies to self-cartilage PGs, although autoantibodies occasionally are present in non-arthritic animals as well. The protease-sensitive auto/arthritogenic epitope(s) is located in, or close to, the chondroitin sulfate (CS) attachment region of the PG molecule. The primary structure of the core protein is responsible for the autoimmune/arthritogenic effect of this select group of PGs, whereas the core protein epitopes are masked by glycosaminoglycan (GAG)-side chains. The CS side chains seem to inhibit antigen recognition in all aggrecans with arthritogenic potential, whereas a similar effect with keratan sulfate (KS) appears only in PGs of aging cartilages.
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PMID:Mapping of arthritogenic/autoimmune epitopes of cartilage aggrecans in proteoglycan-induced arthritis. 753 28


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