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EN
The mechanisms underlying cartilage matrix degradation in joint diseases is not fully understood but reactive oxygen species are implicated as main causative factors. Comparative studies of glutathione reductase (GR) activity in synovial fluid from patients with rheumatoid arthritis (RA), reactive arthritis (ReA) and osteoarthritis (OA) as well as correlations between GR activity and concentration of the major cartilage components in synovial fluid are presented in this study. We found significantly higher activity of GR in RA (about three-fold) and ReA (about two-fold) than in OA. In RA and ReA patients, GR activity in synovial fluid correlates negatively with the concentrations of collagen and degradation products of sulfated glycosaminoglycans. In OA patients the activity of GR was significantly lower than in RA and ReA, which positively correlated with the concentration of collagen and showed a tendency for positive correlation with the degradation products of sulfated glycosaminoglycans. Our results suggest that in RA and ReA patients increased activity of GR does not prevent the increased degradation of collagen and proteoglycans by ROS.
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2012
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vol. 59
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issue 4
693-696
EN
Mucopolysaccharidoses (MPS) are severe inherited metabolic disorders caused by storage of glycosaminoglycans (GAGs). The level of accumulated GAGs is an important parameter in assessment of the severity of the disease and the efficacy of treatment; unfortunately, biochemical methods are often unreliable and only semi-quantitative. Therefore, finding other methods for estimation of GAG levels and/or assessment of the efficacy of applied therapy is very important. Although monitoring of GAG levels during therapy is crucial, in this work it is proposed that analysis of the ultrastructure of MPS cells by electron microscopic techniques can be considered as an alternative and reliable method for assessment of lysosomal storage. The number of complex lysosomal structures was found to be significantly higher in MPS cells relative to controls, while it decreased significantly in response to either enzyme replacement therapy or substrate reduction therapy. Thus, this parameter, easily assessed by electron microscopy, appears to correspond to the physiological state of MPS cells.
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Proteoglycans of human umbilical cord arteries.

88%
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2000
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vol. 47
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issue 4
1081-1091
EN
Proteoglycans (PGs) were dissociatively extracted from human umbilical cord arteries (UCAs) with 4 M guanidine hydrochloride containing Triton X-100 and protease inhibitors, purified by Q-Sepharose anion exchange chromatography and lyophilized. They were analysed by gel filtration, SDS/PAGE and agarose gel electrophoresis before and after treatment with chondroitinase ABC. It was found that the PG preparation was especially enriched in chondroitin/dermatan sulphate PGs. The predominant PG fraction included small PGs that emerged from Sepharose CL-2B with Kav = 0.74. Their molecular mass, estimated by SDS/PAGE, was 160-200 kDa and 90-150 kDa, i.e. it was typical for biglycan and decorin, respectively. Treatment with chondroitinase ABC yielded the core proteins of 45 and 47 kDa, characteristic for both small PGs. Remarkable amounts of the 45 kDa protein were detected in non-treated PG samples, suggesting the presence of free core proteins of biglycan and decorin. Large PGs were present in lower amounts. In intact form they were eluted from Sepharose CL-2B with Kav = 0.17 and 0.43. Digestion with chondroitinase ABC yielded the core proteins with a molecular mass within the range of 180-360 kDa but predominant were the bands of 200, 250 and 360 kDa. The large PGs probably represent various forms of versican or perlecan bearing chondroitin sulphate chains.
4
88%
EN
Heparan sulfate (HS) is one of the most common glycosaminoglycan (GAG) in mammals. It is composed of relatively simple disaccharide subunits, which, by further modification, such as sulfation and epimerization, potentially offer huge diversity in biological function. GAG chains of different length, different patterns of sulfation, and other modifications, depending on location, generate unique forms. Due to polyanion charges, these compounds can interact with other molecules, such as proteins, cytokines, chemokines and growth factors, both on the cell surface and inside the extracellular matrix. These interactions serve protective and storage functions for the compounds, safeguarding them from proteolysis. In this way, HS is involved in numerous signaling pathways, and in growth and differentiation processes. Disrupted interactions between the HS and growth factors, cytokines or other proteins have been observed in various disorders, among these Alzheimer’s disease, epilepsy, atherosclerosis, diabetes, and cancer processes. Detailed knowledge of these relationships at the molecular level will allow researchers to understand the mechanisms underlying these disorders and enable the development of effective therapeutic strategies.
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2005
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vol. 52
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issue 2
501-507
EN
Proteoglycans of Wharton's jelly contain mainly chondroitin/dermatan sulphate chains. The predominant proteoglycan is decorin (core proteins of 45 and 47 kDa), although the core proteins of biglycan (45 kDa), versican (260 kDa) and of other proteoglycans (90, 110, 220 kDa) were also detected (Gogiel et al., 2003). The aim of the present study was to compare the proteoglycan composition of Wharton's jelly of newborns delivered by healthy mothers and those with pre-eclampsia. Proteoglycans from pre-eclamptic Wharton's jelly had a higher sulphated glycosaminoglycan/protein ratio than those of normal tissue. Pre-eclampsia is associated with a lower level of all proteoglycan core proteins, especially those of higher molecular mass (such as versican), although the same set of core proteins were found in normal and pre-eclamptic Wharton's jelly. The alterations in the proteoglycan composition of Wharton's jelly may affect the mechanical properties of the umbilical cord and, in the case of pre-eclampsia, disturb foetal blood circulation.
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2001
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vol. 48
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issue 2
563-572
EN
The effect of insulin, wheat germ agglutinin (WGA), peanut agglutinin (PNA) and concanavalin A (ConA) on [3H]glucosamine incorporation into pericellular glycosaminoglycans (GAGs) was investigated in two lines of cultured human dermal fibroblasts. Insulin and WGA stimulated [3H]glucosamine incorporation into hyaluronic acid (HA) and heparan sulphate (HS) without any alteration of chondroitin sulphate (CS) and dermatan sulphate (DS) contents. ConA increased [3H]glucosamine incorporation into HS, CS and DS, but had no effect on [3H]glucosamine incorporation into HA. PNA affected neither the content, nor the composition of GAGs. In contrast to PNA, ConA and WGA stimulated glycolysis and demonstrated an evident antiproliferative effect on dermal fibroblasts. Thus, both the insulin-like action of WGA and ConA on cultured dermal fibroblasts and the differences between the effects of lectins on modulation of GAGs synthesis appear to be determined by their chemical structure.
PL
Glikozoaminoglikany (glycosaminoglycans – GAGs) są grupą heteropolisacharydów, w której skład wchodzą: siarczany chondroityny, siarczany dermatanu, siarczany heparanu, heparyny, siarczany keratanu oraz kwas hialuronowy. GAGs zbudowane są z ujemnie naładowanych łańcuchów polisacharydowych, złożonych z powtarzających się jednostek disacharydowych, do których należą reszty N-acetylowanej heksozoaminy – D-glukozoaminy lub D-galaktozoaminy – albo N-siarczanowanej D-glukozoaminy oraz reszty kwasu heksuronowego – D-glukuronowego lub L-iduronowego – albo galaktozy. Wszystkie GAGs, z wyjątkiem kwasu hialuronowego, posiadają grupę siarczanową oraz tworzą, po przyłączeniu do białek rdzeniowych, proteoglikany (proteoglycans – PGs). GAGs pełnią wiele ważnych biologicznych funkcji, determinujących funkcje PGs. Te ostatnie są obecne we wszystkich rodzajach tkanek, uczestniczą w procesach migracji, proliferacji i różnicowania komórek. Występują głównie w macierzy pozakomórkowej (extracellular matrix – ECM), biorąc udział w organizacji ECM, kształtując jej strukturę i właściwości mechaniczne. Pełnią istotną rolę w utrzymaniu homeostazy, a także wywierają wpływ na szereg procesów metabolicznych, takich jak mineralizacja kości i krzepnięcie krwi. PGs (ze względu na silnie ujemny ładunek łańcuchów glikanowych) biorą udział w selektywnej przepuszczalności błon komórkowych. Składniki ECM, w tym GAGs, odgrywają rolę strukturalno-czynnościową podczas gojenia się uszkodzeń tkankowych. Regulują proces gojenia poprzez stanowienie rezerwuaru i modulatora dla cytokin i czynników wzrostu oraz pełnią funkcje strukturalne poprzez wypełnianie ubytków tkankowych podczas procesu naprawczego.
EN
Glycosaminoglycans (GAGs) are a group of heteropolysaccharides, which include: chondroitin sulfates, dermatan sulfates, heparan sulfates, heparin, keratan sulfates, and hyaluronic acid. GAGs are composed of negatively charged polysaccharide chains composed of repeating disaccharide units, which include N-acetylated hexosamine residues – D-glucosamine or D-galactosamine – or N-sulfated D-glucosamine and hexuronic acid residues – D-glucuronic or L-iduronic acid – or galactose. All GAGs, except for hyaluronic acid, have a sulfate group and form proteoglycans (PGs) when attached to the core proteins. GAGs have many important biological functions influencing PGs functions. PGs are present in all types of tissues and participate in cell migration, proliferation, and differentiation. They occur mainly in the extracellular matrix (ECM), where they participate in ECM organization, structure formation and mechanical properties. They play an important role in maintaining homeostasis and also influence metabolic processes, such as bone mineralization and blood coagulation. PGs (due to the strongly negative charge of the glycan chains) are involved in the selective permeability of cell membranes. Components of the ECM, including GAGs, play a structural and functional role during the healing of tissue damage. They regulate the healing process by acting as a reservoir and modulator for cytokines and growth factors and perform structural functions by filling tissue defects during the repair process.
EN
Glycosaminoglycans (GAGs) are a group of heteropolysaccharides, which include: chondroitin sulfates, dermatan sulfates, heparan sulfates, heparin, keratan sulfates, and hyaluronic acid. GAGs are composed of negatively charged polysaccharide chains composed of repeating disaccharide units, which include N-acetylated hexosamine residues – D-glucosamine or D-galactosamine – or N-sulfated D-glucosamine and hexuronic acid residues – D-glucuronic or L-iduronic acid – or galactose. All GAGs, except for hyaluronic acid, have a sulfate group and form proteoglycans (PGs) when attached to the core proteins. GAGs have many important biological functions influencing PGs functions. PGs are present in all types of tissues and participate in cell migration, proliferation, and differentiation. They occur mainly in the extracellular matrix (ECM), where they participate in ECM organization, structure formation and mechanical properties. They play an important role in maintaining homeostasis and also influence metabolic processes, such as bone mineralization and blood coagulation. PGs (due to the strongly negative charge of the glycan chains) are involved in the selective permeability of cell membranes. Components of the ECM, including GAGs, play a structural and functional role during the healing of tissue damage. They regulate the healing process by acting as a reservoir and modulator for cytokines and growth factors and perform structural functions by filling tissue defects during the repair process.
PL
Glikozoaminoglikany (glycosaminoglycans – GAGs) są grupą heteropolisacharydów, w której skład wchodzą: siarczany chondroityny, siarczany dermatanu, siarczany heparanu, heparyny, siarczany keratanu oraz kwas hialuronowy. GAGs zbudowane są z ujemnie naładowanych łańcuchów polisacharydowych, złożonych z powtarzających się jednostek disacharydowych, do których należą reszty N-acetylowanej heksozoaminy – D-glukozoaminy lub D-galaktozoaminy – albo N-siarczanowanej D-glukozoaminy oraz reszty kwasu heksuronowego – D-glukuronowego lub L-iduronowego – albo galaktozy. Wszystkie GAGs, z wyjątkiem kwasu hialuronowego, posiadają grupę siarczanową oraz tworzą, po przyłączeniu do białek rdzeniowych, proteoglikany (proteoglycans – PGs). GAGs pełnią wiele ważnych biologicznych funkcji, determinujących funkcje PGs. Te ostatnie są obecne we wszystkich rodzajach tkanek, uczestniczą w procesach migracji, proliferacji i różnicowania komórek. Występują głównie w macierzy pozakomórkowej (extracellular matrix – ECM), biorąc udział w organizacji ECM, kształtując jej strukturę i właściwości mechaniczne. Pełnią istotną rolę w utrzymaniu homeostazy, a także wywierają wpływ na szereg procesów metabolicznych, takich jak mineralizacja kości i krzepnięcie krwi. PGs (ze względu na silnie ujemny ładunek łańcuchów glikanowych) biorą udział w selektywnej przepuszczalności błon komórkowych. Składniki ECM, w tym GAGs, odgrywają rolę strukturalno-czynnościową podczas gojenia się uszkodzeń tkankowych. Regulują proces gojenia po-przez stanowienie rezerwuaru i modulatora dla cytokin i czynników wzrostu oraz pełnią funkcje strukturalne poprzez wypełnianie ubytków tkankowych podczas procesu naprawczego.
EN
Glycosaminoglycans (gag) performs a great role in atherosclerosis, diabetic nephropathy, venous insuffi ciency, crural ulceration, uric acid diathesis, mucopolysaccharidosis, arthritis, osteitis, neoplasms, thyroid and kidney diseases. Disorders of the gag level are connected with disorders of metabolism of proteoglycans and hepar disfunction. Gag are characterized by a considerable heterogeneity.
PL
Glikozaminoglikany (gag) odgrywają dużą rolę w patogenezie miażdżycy, nefropatii cukrzycowej, niewydolności żylnej, owrzodzeniach podudzi, skazie moczanowej, mukopolisacharydozie, zapaleniu stawów, zapaleniu kości, nowotworach, chorobach tarczycy i nerek. Zaburzenia dotyczące zmiany stężenia gag są prawdopodobnie wynikiem zaburzeń w metaboliźmie proteoglikanów, jak i związane są z dysfunkcją wątroby. Gag charakteryzuje znaczna heterogenność.
EN
Hyaluronic acid (HA) is a polysaccharide (glycosaminoglycan), which is normally present in all living organisms. Its chemical constitution is identical in mammals and bacteria. This mucopolisaccharide chain may consist of even several thousands of saccharide subunits. The unique, highly elastic nature of HA, together with its bio-compatibility and the lack of immunogenic potential in relation to the human body, have contributed to the widespread use of this substance in many clinical solutions including supplementation of the synovial fluid in patients with joint inflammation as an adjuvant agent in ophthalmic and dental surgery and the preparation accelerating postoperative wound healing. Recent studies assess the properties of HA, a potential drug carrier in various applications including eye drops, inhalations, parenteral and local application and as a carrier for oncological agents. The aim of the study based on the analysis of available literature was to explain the construction, metabolism and potential of HA application in the treatment of selected disease units, including orthopedic and oncological conditions.
PL
Kwas hialuronowy (HA) jest poliwęglowodanem, mukopolisacharydem (glikozoaminoglikanem), występującym naturalnie we wszystkich organizmach żywych. Ma identyczną budowę chemiczną zarówno u ssaków, jak i u bakterii. Łańcuch tego mukopolisacharydu może składać się nawet z kilku tysięcy podjednostek cukrowych. Unikalny wysokoelastyczny charakter HA, wraz z jego biozgodnością i brakiem potencjału immunogennego w stosunku do organizmu człowieka, przyczyniły się do zastosowania tej substancji w wielu rozwiązaniach klinicznych, w tym suplementacji płynu stawowego u pacjentów z zapaleniem stawów, jako środek pomocniczy w chirurgii okulistycznej i stomatologicznej oraz preparat przyspieszający gojenie ran pooperacyjnych. W ostatnich latach, w badaniach naukowych ocenia się właściwości HA jako potencjalnego nośnika leków w różnych drogach podania, w tym krople do oczu, do nosa, podane drogą wziewną, zastosowanie pozajelitowe i miejscowe oraz jako nośnika dla leków nowotworowych. Celem pracy, opartej na analizie dostępnej literatury, jest wyjaśnienie budowy, metabolizmu i możliwości wykorzystania HA w terapii wybranych jednostek chorobowych – w tym ortopedii i onkologii.
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