Impaired degradation of keratan sulphate by Morquio A fibroblasts

Glössl, Josef; Kresse, Hans

doi:10.1042/bj2030335

Cited by 53 publications

(46 citation statements)

References 18 publications

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“…The data presented in the current study may indicate that galactosaminoglycans and/or glycosyltransferases participating in chondroitin chain biosynthesis perform a chaperone-like function. In the presence of tunicamycin, earlier studies show secretion of decorin by human fibroblast or chondrocytes (56,57). In addition, undersulfated proteoglycans were secreted by cultured chondrocytes in the presence of either monesin, an inhibitor of protein secretion, or brefeldin A, an inhibitor of vesicular transport and secretion of macromolecules (58,59).…”

Section: Discussionmentioning

confidence: 99%

Decorin Core Protein Secretion Is Regulated by N-Linked Oligosaccharide and Glycosaminoglycan Additions

Seo

Hocking

Höök

et al. 2005

Journal of Biological Chemistry

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Expression of decorin using the vaccinia virus/T7 expression system resulted in secretion of two distinct glycoforms: a proteoglycan substituted with a single chondroitin sulfate chain and N-linked oligosaccharides and a core protein glycoform substituted with N-linked glycans but without a glycosaminoglycan chain. In this report, we have addressed two distinct questions. What is the ratelimiting step in glycosaminoglycan synthesis? Is glycosylation with either N-linked oligosaccharides or glycosaminoglycan required for secretion of decorin? N-terminal sequencing of the core protein glycoform, the addition of benzyl-␤-D-xyloside, and a UDP-xylose: core protein ␤-D-xylosyltransferase activity assay show that xylosylation is a rate-limiting step in chondroitin sulfate biosynthesis. Decorin can be efficiently secreted with N-linked oligosaccharides alone or with a single chondroitin sulfate chain alone; however, there is severely impaired secretion of core protein devoid of any glycosylation. A decorin core protein mutant devoid of N-linked oligosaccharide attachment sites will not be secreted by Chinese hamster ovary cells deficient in xylosyltransferase or by parental Chinese hamster ovary wild type cells if the xylosyltransferase recognition sequence is disrupted. This finding suggests that quality control mechanisms sensitive to an absence of N-linked oligosaccharides can be abrogated by interaction of the core protein with the glycosaminoglycan synthetic machinery. We propose a model of regulation of decorin secretion that has several components, including appropriate substitution with N-linked oligosaccharides and factors involved in glycosaminoglycan synthesis.

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Section: Discussionmentioning

confidence: 99%

Decorin Core Protein Secretion Is Regulated by N-Linked Oligosaccharide and Glycosaminoglycan Additions

Seo

Hocking

Höök

et al. 2005

Journal of Biological Chemistry

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“…EA.hy 926 cells were cultured on plastic or on collagen as described and subsequently preincubated with IL-10 and IL-6 for 8 h. Interleukins were renewed, and cells were metabolically labeled with [ 3 H]leucine (20 Ci/ml of medium, ICN Biomedical, Eschwege, Germany) for 16 h. Immunoprecipitations were carried out as described previously with a monospecific rabbit anti-human decorin antiserum (16). When indicated, samples were digested with chondroitin ABC lyase and subjected to SDS-PAGE under reducing conditions.…”

Section: Methodsmentioning

confidence: 99%

Interleukin (IL)-6 and IL-10 Induce Decorin mRNA in Endothelial Cells, but Interaction with Fibrillar Collagen Is Essential for Its Translation

Strazynski

Eble

Kresse

et al. 2004

Journal of Biological Chemistry

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Decorin, a small multifunctional proteoglycan, is expressed by sprouting endothelial cells (ECs) during inflammation-induced angiogenesis in vivo and by human ECs co-cultured with fibroblasts in a collagen lattice. To investigate how decorin is induced, human EA.hy 926 ECs and/or human umbilical vein ECs were treated with interleukin (IL)-10 and IL-6. Both treatments induced decorin mRNA in human ECs. IL-6 and IL-10 led to a dose-dependent mRNA increase with a maximum at 10 and 50 ng/ml, respectively. The combination of both interleukins together had a stronger effect than one alone. Immunostaining demonstrated that both interleukins caused decorin synthesis in ECs and the formation of capillary-like structures in a collagen lattice. However, immunoprecipitations of interleukin-treated ECs cultured on plastic were negative. Only interleukin-stimulated ECs grown on a collagen type I matrix or growth factor-reduced Matrigel were able to synthesize the proteoglycan. Acid-soluble collagen type I did not support decorin protein synthesis. The addition of antibodies to ␣ 1 or ␣ 2 integrins or the ␣ 2 integrin inhibitor rhodocetin led to an inhibition of synthesis. These data show that IL-10 and IL-6 induce decorin mRNA transcription, but additional signals from the extracellular matrix are necessary for its translation.

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“…The absence of GALNS activity results in impaired catabolism of two glycosaminoglycans (GAGs), keratin sulphate and chondroitin-6-sulphate (Dorfman et al 1976;Gl€ ossl and Kresse 1982). The progressive accumulation of GAGs in various tissues means that the disease affects multiple body systems.…”

Section: Introductionmentioning

confidence: 99%

Mortality in Patients with Morquio Syndrome A

2014

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Background: Morquio syndrome A (mucopolysaccharidosis type IVA) is an autosomal recessive, lifelimiting lysosomal storage disease characterized by deficient activity of the enzyme galactosamine-6-sulfatase. The disease affects multiple body systems, and patients require multidisciplinary care from an early age.Methods: To better understand the natural progression of the disease, life expectancy and common causes of death, death certificates were evaluated for 27 patients (15 male, 12 female) with Morquio syndrome A in the UK, covering the years 1975-2010.Results: Mean age at death (AEstandard deviation) was 25.30 AE 17.43 years, with female patients living longer than male patients (26.55 AE 12.28 years versus 22.95 AE 17.63 years, respectively). Respiratory failure was the primary cause of death in nearly two-thirds of patients (63%). Other causes of death were cardiac failure (11%), post-traumatic organ failure (11%), complications of surgery (11%) and myocardial infarction (4%). Life expectancy increased gradually over time (R 2 ¼ 0.0963), and mean age at death due to respiratory failure improved from 17.42 AE 9.54 years in the 1980s to 30.74 AE 10.84 years in the 2000s. Conclusions:The current data suggest that survival of patients with Morquio syndrome A in the UK has improved in recent decades. It is possible that improvements in multidisciplinary care and referral of patients to specialist centres underlie this trend. It is hoped that novel diseasespecific treatments such as enzyme replacement therapy and haematopoietic stem cell therapy will help to extend the lifespan of patients with Morquio syndrome further still.

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Impaired degradation of keratan sulphate by Morquio A fibroblasts

Cited by 53 publications

References 18 publications

Decorin Core Protein Secretion Is Regulated by N-Linked Oligosaccharide and Glycosaminoglycan Additions

Decorin Core Protein Secretion Is Regulated by N-Linked Oligosaccharide and Glycosaminoglycan Additions

Interleukin (IL)-6 and IL-10 Induce Decorin mRNA in Endothelial Cells, but Interaction with Fibrillar Collagen Is Essential for Its Translation

Mortality in Patients with Morquio Syndrome A

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