Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels
Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-ac...
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| Language: | English |
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Elsevier
2017-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426917300265 |
| _version_ | 1818506986279403520 |
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| author | Bruna Donida Desirèe P. Marchetti Carlos Eduardo Diaz Jacques Graziela Ribas Marion Deon Paula Manini Helen Tais da Rosa Dinara Jaqueline Moura Jenifer Saffi Roberto Giugliani Carmen Regla Vargas |
| author_facet | Bruna Donida Desirèe P. Marchetti Carlos Eduardo Diaz Jacques Graziela Ribas Marion Deon Paula Manini Helen Tais da Rosa Dinara Jaqueline Moura Jenifer Saffi Roberto Giugliani Carmen Regla Vargas |
| author_sort | Bruna Donida |
| collection | DOAJ |
| description | Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder. |
| first_indexed | 2024-12-10T22:12:22Z |
| format | Article |
| id | doaj.art-fe0ec210696843fbbba3498aa68f3530 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-10T22:12:22Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-fe0ec210696843fbbba3498aa68f35302022-12-22T01:31:35ZengElsevierMolecular Genetics and Metabolism Reports2214-42692017-06-0111C465310.1016/j.ymgmr.2017.04.005Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levelsBruna Donida0Desirèe P. Marchetti1Carlos Eduardo Diaz Jacques2Graziela Ribas3Marion Deon4Paula Manini5Helen Tais da Rosa6Dinara Jaqueline Moura7Jenifer Saffi8Roberto Giugliani9Carmen Regla Vargas10Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Porto Alegre, RS, BrazilPrograma de Pós Graduação em Saúde da Criança e do Adolescente, UFRGS, Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Porto Alegre, RS, BrazilLaboratório de Genética Toxicológica, UFCSPA, Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Porto Alegre, RS, BrazilLaboratório de Genética Toxicológica, UFCSPA, Porto Alegre, RS, BrazilLaboratório de Genética Toxicológica, UFCSPA, Porto Alegre, RS, BrazilServiço de Genética Médica, HCPA, Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Porto Alegre, RS, BrazilMorquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.http://www.sciencedirect.com/science/article/pii/S2214426917300265Mucopolysaccharidosis type IVAMorquio A syndromeOxidative stressKeratan sulfateN-acetyl-galactosamine-6-sulfatase |
| spellingShingle | Bruna Donida Desirèe P. Marchetti Carlos Eduardo Diaz Jacques Graziela Ribas Marion Deon Paula Manini Helen Tais da Rosa Dinara Jaqueline Moura Jenifer Saffi Roberto Giugliani Carmen Regla Vargas Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels Molecular Genetics and Metabolism Reports Mucopolysaccharidosis type IVA Morquio A syndrome Oxidative stress Keratan sulfate N-acetyl-galactosamine-6-sulfatase |
| title | Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels |
| title_full | Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels |
| title_fullStr | Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels |
| title_full_unstemmed | Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels |
| title_short | Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels |
| title_sort | oxidative profile exhibited by mucopolysaccharidosis type iva patients at diagnosis increased keratan urinary levels |
| topic | Mucopolysaccharidosis type IVA Morquio A syndrome Oxidative stress Keratan sulfate N-acetyl-galactosamine-6-sulfatase |
| url | http://www.sciencedirect.com/science/article/pii/S2214426917300265 |
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