Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of all-trans retinoic acid on glycosaminoglycan (GAG) accumulation were determined in cultured primary human skin fibroblasts. Confluent cultures treated with retinoic acid accumulated less [3H]GAG than those without the compound, an effect with an apparent threshold of 10 nM which was dose dependent in the concentration range tested (0-10 microM). At 10 microM, the inhibition was 54%. Greater than 80% of the labeled macromolecular material was streptomyces hyaluronidase digestible in cultures labeled with [3H]acetate. The incorporation of H2[35S]O4 into chondroitin sulfate and dermatan sulfate was unaffected, as was total protein synthesis. Retinol also inhibited accumulation of [3H]GAG, but was far less potent. T3 and dexamethasone can inhibit [3H]hyaluronate synthesis. When retinoic acid was added to cultures treated with either of these hormones at concentrations that maximally inhibit [3H] GAG accumulation, there was a further decrease in the rate of macromolecular accumulation. The retinoic acid effect evolved over 24-48 h after addition to the culture medium. A pulse-chase study failed to demonstrate any effect on [3H]GAG degradation.
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PMID:Retinoic acid inhibition of hyaluronate synthesis in cultured human skin fibroblasts. 230 23

The effect of beta-all-trans-retinoic acid (RA) on the synthesis of cellular, cell surface, and secreted glycoconjugates by human Hs705 chondrosarcoma and Hs791 osteosarcoma cells was investigated in vitro. Untreated and RA-treated cells were labeled either metabolically with radioactive precursors or by oxidation of externally exposed cell membrane glycoprotein(s) (GP) by treatment with NalO4 or neuraminidase and galactose oxidase followed by reduction with NaB[3H]4. The cells were solubilized and analyzed by polyacrylamide gel electrophoresis followed by fluorography. RA enhanced the labeling of sialic acid and galactose residues on the GP of relative molecular weight(s) (Mr) in the range 95,000-300,000 on the surfaces of both cell types. [3H]glycosamine incorporation into GP with Mr of 100,000, 150,000, and 190,000 in both cell lines was also stimulated. In the Hs705 cells there was also an increase in the labeling of a 290,000-Mr GP. In contrast, [3H]glucosamine incorporation into glycoconjugates greater than 400,000 Mr in both the cells and the conditioned medium of Hs705 cells decreased. The latter glycoconjugates were susceptible to hyaluronidase and chondroitinases. [3H]glucosamine incorporation into a secreted 230,000-Mr GP, identified as fibronectin, was also reduced. Analyses of conditioned media of cells labeled with [35S]methionine or [14C]proline demonstrated that RA decreased the secretion of procollagen chains and fibronectin. Immunofluorescence revealed that RA alters the distribution of cell-associated fibronectin. These results demonstrated that RA increases the glycosylation of specific cellular and cell surface GP and decreases the production of secreted GP and glycosaminoglycans by the sarcoma cells.
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PMID:Modulation by retinoic acid of cellular, surface-exposed, and secreted glycoconjugates in cultured human sarcoma cells. 658 9

To treat cancer cells overexpressing P-glycoprotein (P-gp), we propose a new concept using a nanodrug. The nanodrug was prepared from polyethyleneimine (PEI)/all-trans retinoic acid (ATRA) conjugates (PRA) and covered with hyaluronic acid (HA) to control the cytotoxicity of PRA (yielding PRA-H). The size distribution of PRA-H was narrow, with an average particle size of approximately 143 nm. Its superior stability in phosphate-buffered saline (PBS) was verified by monitoring changes in particle size and zeta potential for 24 h, which were negligible. In contrast, PEI-H (not conjugated with ATRA) exhibited a significant change in particle size and zeta potential. Although PRA was highly cytotoxic against HCT-8 and SNU-484 cancer cells, both of which overexpress P-gp, the cytotoxicity was significantly reduced by shielding with HA. The cytotoxicity of PRA-H was recovered by treatment with hyaluronidase (HAase), which degrades HA and is present in tumors at high concentrations. These results were confirmed by optical microscopy, fluorescence-activated cell sorting (FACs) analysis, and confocal microscopy. The cytotoxic mechanism of PRA was revealed as a type of necrotic lysis by FACs analysis with propidium iodide (PI) staining. Furthermore, PRA increased HCT-8 cell (colon cancer) permeability to doxorubicin (DOX). Therefore, we concluded that PRA-H is a promising new candidate for the treatment of cells with multidrug resistance (MDR) induced by overexpression of P-gp and cancer stem cells.
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PMID:Polycationic nanodrug covered with hyaluronic acid for treatment of P-glycoprotein overexpressing cancer cells. 2068 38