Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human eosinophils were cultured for up to 7 days in enriched medium in the absence or presence of recombinant human interleukin (IL) 3, mouse IL 5, or recombinant human granulocyte/macrophage colony stimulating factor (GM-CSF) and then were radiolabeled with [35S]sulfate to characterize their cell-associated proteoglycans. Freshly isolated eosinophils that were not exposed to any of these cytokines synthesized Mr approximately 80,000 Pronase-resistant 35S-labeled proteoglycans which contained Mr approximately 80,000 glycosaminoglycans. RNA blot analysis of total eosinophil RNA, probed with a cDNA that encodes a proteoglycan peptide core of the promyelocytic leukemia HL-60 cell, revealed that the mRNA which encodes the analogous molecule in eosinophils was approximately 1.3 kilobases, like that in HL-60 cells. When eosinophils were cultured for 1 day or longer in the presence of 10 pM IL 3, 1 pM IL 5, or 10 pM GM-CSF, the rates of [35S]sulfate incorporation were increased approximately 2-fold, and the cells synthesized Mr approximately 300,000 Pronase-resistant 35S-labeled proteoglycans which contained Mr approximately 30,000 35S-labeled glycosaminoglycans. Approximately 93% of the 35S-labeled glycosaminoglycans bound to the proteoglycans synthesized by noncytokine- and cytokine-treated eosinophils were susceptible to degradation by chondroitinase ABC. As assessed by high performance liquid chromatography, 6-16% of these chondroitinase ABC-generated 35S-labeled disaccharides were disulfated disaccharides derived from chondroitin sulfate E; the remainder were monosulfated disaccharides derived from chondroitin sulfate A. Utilizing GM-CSF as a model of the cytokines, it was demonstrated that the GM-CSF-treated cells synthesized larger glycosaminoglycans onto beta-D-xyloside than the noncytokine-treated cells. Thus, IL 3, IL 5, and GM-CSF induce human eosinophils to augment proteoglycan biosynthesis by increasing the size of the newly synthesized proteoglycans and their individual chondroitin sulfate chains.
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PMID:Characterization of a human eosinophil proteoglycan, and augmentation of its biosynthesis and size by interleukin 3, interleukin 5, and granulocyte/macrophage colony stimulating factor. 245 54

The extracellular pH is locally decreased in advanced atherosclerotic lesions, particularly in lipid-rich areas of the lesions. Since accumulation of LDL-derived cholesterol and formation of foam cells are key processes in atherogenesis, we tested here the effects of acidic pH on the uptake of native LDL. First, human monocytes were differentiated into macrophages in the presence of granulocyte-monocyte-colony stimulating factor (GM-CSF) after which native LDL was applied to the monocyte-derived macrophages at pH 5.5, 6.5, or 7.5 and the binding and uptake of LDL by macrophages were determined. The lower the pH was, the higher was the binding and uptake of LDL by macrophages. Also, acidic pH was found to increase the production of cell surface proteoglycans by macrophages and binding of LDL to the glycosaminoglycan chains of the proteoglycans. The acidity-induced increase in the uptake of LDL by macrophages could be inhibited by pretreating the cells with heparinase and chondroitinase as well as by inhibiting the production of proteoglycans with NaClO(3). Thus, the observed increase in the uptake of native LDL to macrophages appears to depend on the increased ability of LDL to bind to cell surface proteoglycans at acidic pH. Taken together, our present results indicate that acidity increases the effective concentration of LDL on macrophage surfaces by increasing the amount of cell surface proteoglycans and by enhancing the binding of LDL to them and so promotes LDL uptake with ensuing foam cell formation.
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PMID:Acidity increases the uptake of native LDL by human monocyte-derived macrophages. 2157 Dec 77