Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the avian viral oncogenes src and myc were compared for their ability to alter the differentiated phenotype and the proliferative capacity of definitive chondroblasts. As previously demonstrated, viruses carrying the src oncogene suppressed the synthesis of the chondroblast-specific products, type II collagen and cartilage-specific sulfated proteoglycan. In contrast, infection with MC29 and HB1 viruses, which carry the myc oncogene, did not suppress the synthesis of these normal differentiated cell products, but the infected cells exhibited an increased proliferative potential. The MH2 virus, which carries both the myc and mil oncogenes, both induced the suppression of these chondroblast-specific products and increased cell proliferation. The implications of these results for cooperation between oncogenes and the multi-oncogene models for neoplastic transformation are discussed.
Mol Cell Biol 1985 Mar
PMID:myc and src oncogenes have complementary effects on cell proliferation and expression of specific extracellular matrix components in definitive chondroblasts. 298 57

Both retinoids and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit expression of the differentiated phenotype by rabbit costal chondrocytes in culture, as judged by morphological changes and decreased sulfation of glycosaminoglycans (GAG). However, the inhibition of the differentiated phenotype of chondrocytes in TPA-treated cells is restored by parathyroid hormone (PTH), while the inhibition by retinoids is not [Takigawa et al. (1982) Mol. Cell. Biochem. 42, 145-153; Takigawa et al. (1983) Cell Differ. 13, 283-291]. In the present study, we examined the difference between TPA-treated chondrocytes and retinoic acid-treated chondrocytes to determine the mechanism of the restoration of the differentiated phenotype in de-differentiated cells treated with TPA. PTH increased the activity of ornithine decarboxylase [ODC; EC 4.1.1.17], a rate limiting enzyme of polyamine biosynthesis, and proteoglycan synthesis in chondrocytes pretreated with TPA as well as in normal chondrocytes. The maximal stimulations of ODC activity and GAG synthesis were observed 4 h and 24-36 h, respectively, after addition of PTH. The dose-response curve for ODC induction by PTH was parallel to that of PTH-stimulated proteoglycan synthesis both in TPA-treated chondrocytes and in normal chondrocytes. PTH also increased the intracellular cyclic AMP level after 2 min in TPA-treated cells as in normal cells. Addition of dibutyryl cyclic AMP (DBcAMP) induced ODC and restored proteoglycan synthesis in TPA-treated cells. The dose-response curve for induction of ODC by DBcAMP was parallel to that of DBcAMP-stimulated proteoglycan synthesis in both TPA-treated chondrocytes and normal chondrocytes. On the other hand, the increases by PTH in the intracellular cyclic AMP level, ODC activity, and proteoglycan synthesis were inhibited in chondrocytes pretreated with a combination of TPA and retinoic acid as well as in those pretreated with retinoic acid alone. TPA stimulated the syntheses of DNA and RNA in chondrocytes but did not increase the cyclic AMP level or ODC activity. PTH and DBcAMP inhibited the syntheses of DNA and RNA both in TPA-treated cells and in normal cells. These results suggest that ODC induction mediated by elevation of cyclic AMP plays an important role in re-differentiation of de-differentiated cells pretreated with these agents.
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PMID:Comparison of inhibition by a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) of expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture with inhibition by retinoic acid. 300 24

Newborn mice epiphyseal growth plates were preserved by slam freezing/freeze substitution and examined by conventional electron microscopy, stereopsis, high voltage electron microscopy, and electron spectroscopic imaging (ESI). To illustrate the improved ultrastructure of this cryogenic procedure, conventional, aqueously fixed growth plates were included showing collapsed hypertrophic chondrocytes surrounded by a depleted and condensed extracellular matrix. In contrast, the cryogenically prepared epiphyses contain chondrocytes and extracellular matrix vesicles both in direct contact with proteoglycan filaments retained in an expanded state. ESI is an electron microscopic technique which enables the direct localization of atomic elements superimposed over fine structural details. This technique was used to examine the colocalization of calcium and phosphorus within matrix vesicles and within their associated extracellular environments. Matrix vesicles appeared in three distinct diameter ranges. The integrity of the matrix vesicles was examined at various stages of mineralization and also within the mineralized zone of provisional calcification.
J Ultrastruct Mol Struct Res 1988 Jan
PMID:An electron microscopic and spectroscopic study of murine epiphyseal cartilage: analysis of fine structure and matrix vesicles preserved by slam freezing and freeze substitution. 335 53

In contrast to glutaraldehyde-fixed vascular tissue with or without staining with cationic dye, the nonfibrous extracellular matrix of fast-frozen, freeze-dried rabbit aorta and renal artery contained a continuous reticulum of fine filaments, closely associated with collagen, elastin, and smooth muscle cells. Three morphologically distinct types of filament were distinguished; one type was selectively sensitive to chondroitinase ABC degradation, and therefore contains chondroitin and/or dermatan sulfate. The remaining filaments of the reticulum may represent the protein core of the proteoglycan monomer, and the hyaluronic acid backbone of the aggregate. Filaments associated with the surface of smooth muscle cells were usually linked to a continuous filament parallel to the cell surface, which was degraded by heparitinase and therefore contains heparan sulfate. The filaments linked directly to the cell surface were not degraded by either enzyme. The preservation of PG in fast-frozen material provides a significant improvement over that obtained by any presently available technique.
J Ultrastruct Mol Struct Res 1988 Feb
PMID:Proteoglycan in fast-frozen, freeze-dried, plastic-embedded rabbit arteries. 337 71

Cartilage degradation is a characteristic feature of various types of human arthritis, notably rheumatoid arthritis and osteoarthritis. The influence of glucocorticoid and other steroid hormones on cartilage proteoglycan breakdown was examined in a model system in which breakdown is readily quantified by the release of proteoglycan from cultured bovine nasal cartilage discs. Endotoxin (bacterial lipopolysaccharides) treatment enhanced the depletion of cartilage proteoglycan by 2-3 fold. This was inhibited in a concentration-dependent manner by hydrocortisone (10(-9) to 10(-5) M) or other glucocorticoid hormones (dexamethasone, prednisolone, cortisone). Inhibition required the continued presence of the steroid. Removal of hydrocortisone (3 x 10(-7) M) after 4 days from endotoxin-treated cultures resulted in the rapid restoration of an endotoxin response, so that proteoglycan release approached maximum levels during a second 4-day culture period. Other C-21 steroid hormones (progesterone, aldosterone) were also inhibitory at 10(-5) M, but testosterone and beta-estradiol showed little influence on endotoxin action. Proteoglycan products of smaller average mol wt (Sepharose CL-2B chromatography), consistent with core protein cleavages, were released from endotoxin-treated cartilage. Cleavage was unaffected by beta-estradiol, partially blocked by aldosterone and largely prevented by hydrocortisone administration.
Mol Cell Biochem 1988 Jan
PMID:Effect of steroid hormones on endotoxin-mediated cartilage degradation. 337 77

A simple protocol is described that is suitable for the detection of distantly related members of a protein family. In this procedure, similarity to a consensus sequence is used to distinguish chance similarity from similarity due to common ancestry. The consensus sequence is constructed from the sequences of established members of a protein family and it incorporates features characteristic of the protein fold of this family: conserved residues, the pattern of variable and conserved segments, preferred location of gaps etc. The database is searched with the consensus sequence, using the unitary matrix or log odds matrix for scoring the alignments, with variable gap penalty. The advantage of the method is that it weights key residues, ignores sequence similarity in variable segments (thus partially eliminating "background noise" coming from chance similarity), distinguishes gaps disrupting conserved segments from those occurring in positions known to be tolerant of gap events. The utility of the method was demonstrated in the case of the protein family homologous with the internal repeats of complement B as well as the internal repeats identified in fibroblast proteoglycan PG40. The consensus sequence method succeeded in finding some new members of these protein families that could not be detected by earlier methods of sequence comparison.
J Mol Biol 1987 Dec 20
PMID:Detecting homology of distantly related proteins with consensus sequences. 343 Jun 22

We have examined genomic sequences and mRNA species hybridizing to a cDNA clone of a yolk sac carcinoma chondroitin sulfate proteoglycan designated PG19. Genomic blot hybridizations with cDNAs covering the majority of the PG19 mRNA sequence revealed 15 to 17 gene fragments. Similar analysis with probes representing either the propeptide or the combined core protein COOH-terminal domain and 3' untranslated sequences revealed single genomic fragments indicating that a single gene codes for the PG19 proteoglycan. Genomic blot analysis with cDNA sequences coding for the serine-glycine repeat of the core protein identified the same gene fragments observed with the entire PG19 cDNA, indicating that this coding region is homologous with sequences present in multiple genes. The same probes were also used to examine mRNA expression. In addition to the PG19 mRNA, several PG19-related mRNAs could be seen. These PG19-related mRNAs had homology with the serine-glycine coding sequence of the PG19 cDNA. These mRNAs may be coding for proteoglycans. The mRNA coding for PG19 appeared to be uniquely expressed in parietal yolk sac and mast cell lineages. The PG19 mRNA existed in different forms in parietal yolk sac and mast cell lines due to cell-type-specific differences in the length of the 5' untranslated sequences. These results indicate that expression of the PG19 proteoglycan gene is regulated both in terms of cell-type-specific transcription and selection of a transcriptional start site.
Mol Cell Biol 1987 Jan
PMID:Gene expression of the chondroitin sulfate proteoglycan core protein PG19. 356 92

Proteoglycans from human atherosclerotic lesions and from uninvolved aortic intima were isolated and their composition was studied. The tissues were sequentially extracted by guanidine hydrochloride followed by hydrolysis of the tissue by elastase. Chondroitin sulfate/dermatan sulfate proteoglycans were predominant in guanidine hydrochloride extracts of the tissue. Most of the heparan sulfate proteoglycans were released from the tissue by hydrolysis with elastase. The content of proteoglycan material, measured as uronate per unit weight of wet tissue, was lower in fatty streaks and fibrous plaques than in uninvolved tissue (0.58 and 0.48 mg vs. 0.7 mg/g wet tissue). The distribution of different glycosaminoglycans in guanidine hydrochloride-extracted proteoglycans was similar among the lesions and uninvolved tissue, but varied in the elastase-hydrolyzed extracts. Gel filtration studies suggested that the major proteoglycan material, chondroitin sulfate proteoglycans, from lesions had greater molecular weight than proteoglycans from uninvolved tissue. The studies indicate that alteration in intrinsic composition and molecular size of proteoglycans occurs in atherosclerotic lesions.
Exp Mol Pathol 1987 Dec
PMID:Composition of proteoglycans from human atherosclerotic lesions. 367 67

The effect of calcium on cell proliferation and connective tissue formation was studied in cultured vascular smooth muscle cells (SMC) and dermal fibroblasts. Calcium deficiency caused a modest decrease in proliferation of smooth muscle cells but this effect was small compared to that previously observed with fibroblasts. Synthesis of connective tissue components was affected differently in the two cell types. Biosynthesis of proteoglycans was assessed by metabolic labeling of their glycosaminoglycan side chains. Different levels of extracellular calcium did not affect proteoglycan production by fibroblasts, but it was significantly reduced in smooth muscle cells incubated in calcium-deficient medium. Both smooth muscle cells and fibroblasts were able to produce appreciable amounts of collagen in the complete absence of calcium and in both cell types collagen synthesis was increased when calcium was present. Fibroblasts, however, showed a much smaller response to calcium than did smooth muscle cells. In fibroblasts the maximum rate of collagen synthesis was achieved in a narrow range of calcium concentration which was slightly below that found commonly in the tissue culture medium. By contrast, in smooth muscle cells the rate of collagen synthesis increased greatly when calcium was present and this elevated rate persisted even when the cells were exposed to high levels of extracellular calcium. We conclude that these findings may be of significance to the development of atherosclerotic lesions.
Exp Mol Pathol 1986 Jun
PMID:Effect of calcium on cell proliferation and extracellular matrix synthesis in arterial smooth muscle cells and dermal fibroblasts. 372 Sep 19

The proteoglycans and glycosaminoglycans of four human chondrosarcomas with different degrees of malignancy (I-III) have been studied. The hydrodynamic size of proteoglycan subunits and the tissue concentration of total glycosaminoglycans decreased with increasing grade of malignancy. The glycosaminoglycan distribution pattern of all chondrosarcomas showed a similar ratio of chondroitin-4-sulfate:chondroitin-6-sulfate but an increasing portion of keratan sulfate from grade I (6.5%) to grade III (19.2%). Determinations of the molecular weight (Mr values) of glycosaminoglycans were made after 3H labeling by alkaline reduction of proteoglycans in the presence of NaB3H4. The Mr of [3H]chondroitin sulfate isomers decreased markedly from grade I (35,500) to grade III (15,100) while the chain length of [3H]keratan sulfate showed minor variations (Mr 5600-6200). The previously reported decrease in the molecular weight of keratan sulfate with increasing degree of malignancy (S. Pal, W. Strider, R. Margolis, G. Gallo, S. Lee-Huang, and L. Rosenberg, 1978, J. Biol. Chem. 253, 1279-1289) was not observed.
Exp Mol Pathol 1986 Oct
PMID:Isolation and characterization of proteoglycans and glycosaminoglycans from human chondrosarcoma. 377 Jan 41


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