Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The depression of proteoglycan synthesis in ten-day-old high density chondrocyte cultures was shown to be dependent on both the concentration and time of exposure of the cells to hyaluronic acid. Hyaluronic acid had no effect on the overall protein synthesis by the cultured cells. Using benzyl-beta-D-xyloside an exogenous acceptor, it was shown that glycosaminoglycan biosynthesis by the chondrocytes was not affected by hyaluronic acid. It was concluded that hyaluronic acid was effecting glycosaminoglycan chain initiation, hence proteoglycan biosynthesis, either by specifically depressing the synthesis of the core protein or by repressing the activity of the xylosyltransferase.
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PMID:Inhibition of proteoglycan biosynthesis by hyaluronic acid in chondrocytes in cell culture. 13 29

Hydra are characterized by having their body wall organized as an epithelial bilayer with an intervening acellular layer termed the mesoglea. As an extension of the previous study which indicated that mesoglea is a primitive basement membrane which has retained some characteristics of interstitial extracellular matrix, the present study was undertaken to analyze the role of mesoglea components during head regeneration in Hydra vulgaris. Studies were conducted that utilized drugs that affect collagen processing or secondary collagen structure (beta-aminoproprionitrile; 2,2'-dipydridyl; and cis-4-hydroxy-L-proline) and a drug that inhibits addition of glycosaminoglycan chains to proteoglycan core proteins (p-nitrophenyl-beta-D-xylopyranoside). These studies indicated that alterations in the structure of collagens or proteoglycans caused blockage of head regeneration in Hydra as monitored over a 48-hr period. Blockage of head regeneration was reversible once the drugs were removed, indicating that the drugs were not having a general toxic effect on the organism. Radiotracer studies also indicated that blockage of head regeneration was not simply due to a general depression of protein synthesis by the drugs. Various controls indicated that each drug was affecting mesoglea components under the conditions utilized in these studies. These observations indicate that preservation of normal mesoglea structure is required for Hydra head regeneration to proceed.
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PMID:Extracellular matrix (mesoglea) of Hydra vulgaris. II. Influence of collagen and proteoglycan components on head regeneration. 174 97

Articular cartilage explants from 3 horses were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan on proteoglycan biosynthesis. Cultures were exposed to concentrations of 0, 50, or 200 micrograms of the drug/ml for either 2 days or 6 days, and labeled with 35S, before measuring the content of sulfated proteoglycan in the culture media and in extracts of cartilage. In a second experiment, the explants were incubated with the isotope and subsequently exposed to the same concentrations of the polysulfated glycosaminoglycan for 4 days. Subsequently, the amount of remaining labeled proteoglycan was determined. Gel filtration chromatography was used to compare the hydrodynamic size of proteoglycans from the cartilage explants in each experiment. Polysulfated glycosaminoglycan caused a dose-dependent depression of sulfated proteoglycan synthesis, which was statistically significant after 6 days of exposure. Radioactive proteoglycan content in explants was similar in the experiment involving isotopic labeling prior to exposure to the drug. Proteoglycan monomer size was similar in all treatment groups. It was concluded that polysulfated glycosaminoglycan caused a modest depression in proteoglycan synthesis, had little effect on endogenous proteoglycan degradation, and did not influence the size of sulfated proteoglycans synthesized by normal equine chondrocytes in explant culture.
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PMID:Influence of polysulfated glycosaminoglycan on equine articular cartilage in explant culture. 176 81

The effects of human recombinant interleukin-1 beta (IL-1 beta) were investigated on recently isolated (1 to 3 weeks) and on well-established (older than 3 weeks) monolayer cultured human articular chondrocytes. IL-1 beta was found to depress 35S-proteoglycan synthesis rates and to enhance prostaglandin E2 (PGE2) production in these monolayer cultured chondrocytes. Induction of 35S-proteoglycan-degradative activity by these cells also occurred in IL-1 beta treated cultures. These "catabolin" -IL-1 activities were observed in recently isolated as well as in well-established "old" cultures. IL-1 beta increased 3H-thymidine incorporation rates in the "old" cultures. However, in recently isolated chondrocytes a dose-dependent reduction of the 3H-thymidine incorporation occurred. The depression of mitotic activity in these cells was partially abolished by indomethacin, indicating that this depression was a PGE2 effect. However, supplementing IL-1 beta with indomethacin did not raise the 3H-thymidine incorporation rates above the control levels. It can be concluded that IL-1 beta in itself is unable to induce proliferation in recently isolated cartilage cells. Our results suggest the possible existence of two different receptors for the different IL-1 beta activities. Hence, human articular chondrocytes respond differently to in vitro IL-1 beta exposure at different stages of differentiation.
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PMID:Influence of human recombinant interleukin-1 beta on human articular cartilage. Mitotic activity and proteoglycan metabolism. 195 99

The effect of niflumic acid on hyaluronic acid and proteoglycan metabolism of human cartilage cells was investigated in vitro. Cartilage cells were obtained from five different donors. Niflumic acid levels used in the test systems ranged from 0 to 22 microgramsr/ml and were comparable to serum concentrations in humans after oral intake. Niflumic acid increased the synthesis rates of proteoglycan in some batches of isolated and monolayer-cultured chondrocytes. The effect on hyaluronate synthesis was less pronounced. The fact that this increase in the synthesis of proteoglycan was restricted to some of the donors whereas isolated cells or tissue samples from other individuals remained unaffected illustrates the heterogeneity of different human donors. Depression of proteoglycan synthesis in the presence of the drug was never observed.
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PMID:Proteoglycan metabolism in isolated chondrocytes from human cartilage. Influence of niflumic acid. 233 50

An apparatus was designed for mechanical compression of cultured articular cartilage explants with acylindrical plain-ended loading head (diameter 2-5 mm) driven by a stepping motor. A load cell under the culture dish was applied for feedback regulation utilizing a microprocessor-based control unit. The operating programs allowed either continuous or cyclic loading, the latter with adjustable loading/resting ratio. The improvements in the present design compared with previously described apparatuses for similar purposes include: (1) the accurately controlled compression by a load cell and a rapid feedback circuit; (2) the wide range of selectable stresses (25 kPa-12.5 MPa) with both continuous and cyclic loading modes; (3) the ability to handle cycles as short as 1 s with 15 ms peak loading phase. Using a 4 s cycle and 0.5 MPa load for 1.5 h resulted in a significantly enhanced incorporation of radiosulphate in cultured bovine articular cartilage explants, suggesting a stimulation of proteoglycan synthesis. Light and scanning electron microscopic examinations revealed a slight depression and superficial alterations in cartilage structure at the impact site following high pressures. We expect that this apparatus will help in revealing how articular cartilage tissue and chondrocytes respond to external mechanical stimuli.
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PMID:A mechanical apparatus with microprocessor controlled stress profile for cyclic compression of cultured articular cartilage explants. 262 30

Knees of mature dogs were immobilized for 6 weeks by long-leg casts allowing 8 degrees-15 degrees of motion, a model studied by others, or with external fixators, a new, more severe model that kept the joints rigid. Some animals were allowed to recover for 1 week after the immobilization period. Articular cartilage was examined histologically and biochemically. After 6 weeks of immobilization, water increased 7% in both casted and fixator-immobilized joints compared with normal knee cartilage, while hexuronic acid was 23 and 28% lower, respectively. The limited motion permitted by the casts resulted in a smaller depression of proteoglycan synthesis and less proteoglycan loss during immobilization than occurred in the rigid external fixator group. The protective effect of limited motion was shown clearly during the recovery period: as measured by hexuronic acid content, cartilage from the casted joints had almost recovered within 1 week, whereas the external fixator group experienced little or no recovery during the week after treatment. In contrast to previous studies by others with casted joints, both newly synthesized [35S]sulfate-labeled and accumulated unlabeled proteoglycans from both casted and fixator-immobilized cartilages were able to form complexes with exogenous hyaluronic acid to the same extent as those from control cartilage. Thus, in immobilized cartilage, failure of the newly synthesized proteoglycan to bind to hyaluronate is not a mechanism of accelerated proteoglycan loss. The accelerated proteoglycan turnover appears to be caused by a combination of decreased synthesis and increased proteolysis of the secreted proteoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical changes in articular cartilage after joint immobilization by casting or external fixation. 270 26

The effect of piroxicam on proteoglycan metabolism of human cartilage cells was investigated in two in vitro models. Cells or tissue samples were obtained from six different donors. Piroxicam levels used in the test systems ranged from 2 to 6 micrograms r/ml and were comparable with serum concentrations in humans after oral intake. Piroxicam increased the synthesis rates of proteoglycan in some batches of isolated and monolayer-cultured chondrocytes and in tissue-cultured articular cartilage. The fact that this increase in the synthesis of proteoglycan was restricted to some of the donors whereas isolated cells or tissue samples from other individuals remained unaffected illustrates the heterogeneity of different human donors. Depression of proteoglycan synthesis in the presence of the drug was not observed.
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PMID:Proteoglycan metabolism in isolated chondrocytes from human cartilage and in short-term tissue-cultured human articular cartilage. 270 16

The effect of lipopolysaccharide preparations from Salmonella enteritidis, Bacteroides gingivalis, and Actinobacillus actinomycetemcomitans on human gingival fibroblasts was studied. Lipopolysaccharide from all sources inhibited fibroblast proliferation in the concentration range of 0.5 to 50 micrograms/ml, with the lipopolysaccharide from A. actinomycetemcomitans having the strongest inhibitory effect. Assessment of the effect of lipopolysaccharide on gingival fibroblast metabolism indicated both total protein and proteoglycan synthesis to be inhibited with increasing concentrations of lipopolysaccharide. As for the antiproliferative effect, lipopolysaccharide from A. actinomycetemcomitans had the greatest inhibitory effect on cell synthetic activity. This inhibitory effect was determined by pulse-chase experiments to be a true depression in synthesis. Furthermore, the effect was independent of lipopolysaccharide-induced changes in cell proliferation and prostaglandin synthesis. This study confirmed the toxic effect of lipopolysaccharide on fibroblasts and, in particular, indicated that various lipopolysaccharide preparations vary in their potency to influence cell proliferation and extracellular matrix synthesis.
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PMID:Effect of lipopolysaccharide on proteoglycan synthesis by adult human gingival fibroblasts in vitro. 316 85

The effects of human recombinant interleukin-1 alpha (IL-1 alpha) on proteoglycan (PG) metabolism of rabbit intervertebral disc were investigated morphologically and biochemically using rabbit annulus fibrosus (AF) cells in culture. AF cells could maintain their differentiated phenotype well in our primary culturing condition. In this situation, IL-1 alpha stimulated the cells and induced marked increase of PG release. Dose dependency of IL-1 alpha on PG release was seen in the concentration range between 5-50 U/ml. Caseinolytic activity produced and secreted into the medium by AF cells was assayed and it was found that IL-1 alpha enhanced the enzyme activities in the medium. The effects of IL-1 alpha on PG and DNA synthesis were also studied. Slight depression was observed in PG synthesis but there was no effect on DNA synthesis. These data suggest that IL-1 alpha may play an important role in PG metabolism of intervertebral disc cells, especially in the catabolic pathway of PG.
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PMID:The role of interleukin-1 on proteoglycan metabolism of rabbit annulus fibrosus cells cultured in vitro. 326 23


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