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  1 / 1351 MEDLINE  
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[PMID]:29233882
[Au] Autor:Seranova E; Connolly KJ; Zatyka M; Rosenstock TR; Barrett T; Tuxworth RI; Sarkar S
[Ad] Endereço:Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
[Ti] Título:Dysregulation of autophagy as a common mechanism in lysosomal storage diseases.
[So] Source:Essays Biochem;61(6):733-749, 2017 12 12.
[Is] ISSN:1744-1358
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The lysosome plays a pivotal role between catabolic and anabolic processes as the nexus for signalling pathways responsive to a variety of factors, such as growth, nutrient availability, energetic status and cellular stressors. Lysosomes are also the terminal degradative organelles for autophagy through which macromolecules and damaged cellular components and organelles are degraded. Autophagy acts as a cellular homeostatic pathway that is essential for organismal physiology. Decline in autophagy during ageing or in many diseases, including late-onset forms of neurodegeneration is considered a major contributing factor to the pathology. Multiple lines of evidence indicate that impairment in autophagy is also a central mechanism underlying several lysosomal storage disorders (LSDs). LSDs are a class of rare, inherited disorders whose histopathological hallmark is the accumulation of undegraded materials in the lysosomes due to abnormal lysosomal function. Inefficient degradative capability of the lysosomes has negative impact on the flux through the autophagic pathway, and therefore dysregulated autophagy in LSDs is emerging as a relevant disease mechanism. Pathology in the LSDs is generally early-onset, severe and life-limiting but current therapies are limited or absent; recognizing common autophagy defects in the LSDs raises new possibilities for therapy. In this review, we describe the mechanisms by which LSDs occur, focusing on perturbations in the autophagy pathway and present the latest data supporting the development of novel therapeutic approaches related to the modulation of autophagy.
[Mh] Termos MeSH primário: Autofagia/fisiologia
Doenças por Armazenamento dos Lisossomos/metabolismo
[Mh] Termos MeSH secundário: Animais
Autofagia/genética
Seres Humanos
Doenças por Armazenamento dos Lisossomos/genética
Lisossomos/metabolismo
Esfingolipidoses/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1042/EBC20170055


  2 / 1351 MEDLINE  
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[PMID]:28456990
[Au] Autor:Verma J; Bijarnia-Mahay S; Verma IC
[Ad] Endereço:Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India.
[Ti] Título:Prenatal Diagnosis of Lysosomal Storage Disorders Using Chorionic Villi.
[So] Source:Methods Mol Biol;1594:265-291, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prenatal enzymatic diagnosis for an array of lysosomal storage disorders (LSDs) can be performed accurately, provided that a confirmed diagnosis by biochemical/molecular study in the index case is available and a strict defined protocol, specific to each individual disorder is followed. The present chapter describes the protocols for reliable and accurate prenatal enzymatic diagnoses by fluorometric and spectrophotometric methods of lysosomal storage disorders: Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandhoff, GM1, Mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy, and Batten diseases using uncultured chorionic villi samples. The biological reference intervals for enzyme levels in normal and affected fetuses are given for interpretation of prenatal results. It is imperative to establish normal reference interval in each laboratory to take into account the local environment, technical variations, and different ethnicities. Besides, enzyme activity in the fetus should be represented as percentage of the mean activity of enzyme of normal fetuses. The pitfalls and challenges in prenatal diagnosis as well as technical problems in performing enzyme assays are also discussed to help the reader in standardization and performing the assays for correct diagnosis.
[Mh] Termos MeSH primário: Vilosidades Coriônicas/enzimologia
Vilosidades Coriônicas/metabolismo
Doenças por Armazenamento dos Lisossomos/diagnóstico
Doenças por Armazenamento dos Lisossomos/enzimologia
Diagnóstico Pré-Natal/métodos
[Mh] Termos MeSH secundário: Feminino
Feto/enzimologia
Feto/metabolismo
Seres Humanos
Gravidez
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_18


  3 / 1351 MEDLINE  
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[PMID]:28456989
[Au] Autor:Sozmen EY; Sezer ED
[Ad] Endereço:Department of Medical Biochemistry and Metabolism Laboratory, Ege University Faculty of Medicine, Izmir, Turkey. eser.sozmen@ege.edu.tr.
[Ti] Título:Methods for Determination of α-Glycosidase, ß-Glycosidase, and α-Galactosidase Activities in Dried Blood Spot Samples.
[So] Source:Methods Mol Biol;1594:255-264, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The lysosomal storage diseases (LDSs) are a heterogeneous group of inherited genetic disorders caused by defects of lysosomal proteins. The accumulation of undigested substrates from different catabolic pathways leads to cellular dysfunction. LSDs generally presents during early childhood and have a devastating impact on the families and on public health. Over the years, approaches for treatment of some LSDs have been developed with different strategies. Increasing availability of treatments of these diseases has accelerated the development of new methods and techniques for rapid diagnosis in patients with clinical indication.The use of dried blood spot (DBS) test has been proposed as a first tier test to identify patients with Gaucher, Pompe, and Fabry diseases. DBS usage is advantageous for the purpose of screening as it is non-invasive, sensitive, has low-cost and fast turnaround time compared to measurements in leucocyte and/or fibroblast culture. This chapter focuses on the activity measurement of three lysosomal enzymes (α-glucosidase, ß-glucosidase, and α galactosidase) in DBS samples by using fluorescent substrates and by the LC-MS/MS (liquid chromatography-mass spectrometry) method. All steps of the methods, from preparation of the solutions to calculation of the enzyme activity, will be explained in detail.
[Mh] Termos MeSH primário: Teste em Amostras de Sangue Seco/métodos
Doenças por Armazenamento dos Lisossomos/enzimologia
alfa-Galactosidase/sangue
alfa-Glucosidases/sangue
[Mh] Termos MeSH secundário: Seres Humanos
Recém-Nascido
Isoenzimas/sangue
Doenças por Armazenamento dos Lisossomos/sangue
Doenças por Armazenamento dos Lisossomos/diagnóstico
Triagem Neonatal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 2HLC17MX9G (agalsidase alfa); EC 3.2.1.20 (alpha-Glucosidases); EC 3.2.1.22 (alpha-Galactosidase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_17


  4 / 1351 MEDLINE  
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[PMID]:28456981
[Au] Autor:Hamill KM; Wexselblatt E; Tong W; Esko JD; Tor Y
[Ad] Endereço:Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093-0358, USA.
[Ti] Título:Delivery of Cargo to Lysosomes Using GNeosomes.
[So] Source:Methods Mol Biol;1594:151-163, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Liposomes have been used to improve the intracellular delivery of a variety of cargos. Encapsulation of cargos in liposomes leads to improved plasma half-lives and minimized degradation. Here, we present a method for improving the selective delivery of liposomes to the lysosomes using a guanidinylated neomycin (GNeo) transporter. The method for synthesizing GNeo-lipids, incorporating them into liposomes, and the enhanced lysosomal delivery of encapsulated cargo are presented. GNeo-liposomes, termed GNeosomes, are capable of delivering a fluorescent dye to the lysosomes of Chinese hamster ovary cells as shown using confocal microscopy. GNeosomes can also be used to deliver therapeutic quantities of lysosomal enzymes to fibroblasts isolated from patients with a lysosomal storage disorder.
[Mh] Termos MeSH primário: Lisossomos/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Células CHO
Cricetinae
Cricetulus
Seres Humanos
Lipossomos/metabolismo
Doenças por Armazenamento dos Lisossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Liposomes)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_9


  5 / 1351 MEDLINE  
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[PMID]:28456978
[Au] Autor:Lund FW; Wüstner D
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230, Odense M, Denmark.
[Ti] Título:Quantitative Co-Localization and Pattern Analysis of Endo-Lysosomal Cargo in Subcellular Image Cytometry and Validation on Synthetic Image Sets.
[So] Source:Methods Mol Biol;1594:93-128, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Late endosomes and lysosomes (LE/LYSs) play a central role in trafficking of endocytic cargo, secretion of exosomes, and hydrolysis of ingested proteins and lipids. Failure in such processes can lead to lysosomal storage disorders in which a particular metabolite accumulates within LE/LYSs. Analysis of endocytic trafficking relies heavily on quantitative fluorescence microscopy, but evaluation of the huge image data sets is challenging and demands computer-assisted statistical tools. Here, we describe how to use SpatTrack ( www.sdu.dk/bmb/spattrack ), an imaging toolbox, which we developed for quantification of the distribution and dynamics of endo-lysosomal cargo from fluorescence images of living cells. First, we explain how to analyze experimental images of endocytic processes in Niemann Pick C2 disease fibroblasts using SpatTrack. We demonstrate how to quantify the location of the sterol-binding protein NPC2 in LE/LYSs relative to cholesterol -rich lysosomal storage organelles (LSOs) stained with filipin. Second, we show how to simulate realistic vesicle patterns in the cell geometry using Markov Chain Monte Carlo and suitable inter-vesicle and cell-vesicle interaction potentials. Finally, we use such synthetic vesicle patterns as "ground truth" for validation of two-channel analysis tools in SpatTrack, revealing their high reliability. An improved version of SpatTrack for microscopy-based quantification of cargo transport through the endo-lysosomal system accompanies this protocol.
[Mh] Termos MeSH primário: Endocitose/fisiologia
Endossomos/metabolismo
Lisossomos/metabolismo
[Mh] Termos MeSH secundário: Animais
Colesterol/metabolismo
Seres Humanos
Doenças por Armazenamento dos Lisossomos/metabolismo
Microscopia de Fluorescência
Método de Monte Carlo
Doenças de Niemann-Pick/metabolismo
Transporte Proteico/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_6


  6 / 1351 MEDLINE  
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[PMID]:29178638
[Au] Autor:von der Lippe C; Diesen PS; Feragen KB
[Ad] Endereço:Centre for Rare Disorders, Oslo University Hospital, Rikshospitalet, P.B. 4950 Nydalen, Oslo, 0424, Norway.
[Ti] Título:Living with a rare disorder: a systematic review of the qualitative literature.
[So] Source:Mol Genet Genomic Med;5(6):758-773, 2017 11.
[Is] ISSN:2324-9269
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Individuals with rare diseases may face challenges that are different from those experienced in more common medical conditions. A wide range of different rare conditions has resulted in a myriad of studies investigating the specificities of the diagnosis in focus. The shared psychological experiences of individuals with a rare condition, however, have not been reviewed systematically. METHODS: We performed a systematic review, including qualitative studies on adults, published between 2000 and 2016. Papers including more than one rare genetic or nongenetic diagnosis were included. Studies based on single diagnoses were excluded except for four specific conditions: hemophilia (bleeding disorder), phenylketonuria (metabolic disorder), Fabry disease (lysosomal storage disorder), and epidermolysis bullosa (skin disorder). RESULTS: The review identified 21 studies. Findings were synthesized and categorized according to three main themes: (1) Consequences of living with a rare disorder, (2) Social aspects of living with a rare disorder, and (3) Experiences with the health care system. Findings point to several unique challenges, such as the psychological, medical, and social consequences of a lack of knowledge about the condition in health care and social settings. CONCLUSION: The findings highlight the need for more research on the shared psychological and social impact of living with a rare diagnosis across conditions, in order to identify risk factors and inform clinical practice.
[Mh] Termos MeSH primário: Família/psicologia
Doenças Raras/patologia
[Mh] Termos MeSH secundário: Adaptação Psicológica
Assistência à Saúde
Hemofilia A/genética
Hemofilia A/patologia
Seres Humanos
Doenças por Armazenamento dos Lisossomos/genética
Doenças por Armazenamento dos Lisossomos/patologia
Doenças Metabólicas/genética
Doenças Metabólicas/patologia
Pesquisa Qualitativa
Doenças Raras/genética
Dermatopatias/genética
Dermatopatias/patologia
Apoio Social
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1002/mgg3.315


  7 / 1351 MEDLINE  
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[PMID]:29235819
[Au] Autor:Olkhovych NV; Gorovenko NG
[Ti] Título:Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.
[So] Source:Ukr Biochem J;88(5):96-106, 2016 Sep-Oct.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may lead to serious diagnostic errors.
[Mh] Termos MeSH primário: Cerebrosídeo Sulfatase/genética
Frequência do Gene
Iduronidase/genética
Doenças por Armazenamento dos Lisossomos/genética
alfa-Galactosidase/genética
alfa-Glucosidases/genética
Cadeia alfa da beta-Hexosaminidase/genética
[Mh] Termos MeSH secundário: Adulto
Alelos
Doenças Assintomáticas
Cerebrosídeo Sulfatase/deficiência
Criança
Diagnóstico Diferencial
Erros de Diagnóstico
Feminino
Expressão Gênica
Haplótipos
Seres Humanos
Iduronidase/deficiência
Doenças por Armazenamento dos Lisossomos/diagnóstico
Doenças por Armazenamento dos Lisossomos/enzimologia
Doenças por Armazenamento dos Lisossomos/epidemiologia
Lisossomos/enzimologia
Masculino
Mutação
Ucrânia/epidemiologia
alfa-Glucosidases/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.6.8 (Cerebroside-Sulfatase); EC 3.2.1.20 (GAA protein, human); EC 3.2.1.20 (alpha-Glucosidases); EC 3.2.1.22 (alpha-Galactosidase); EC 3.2.1.52 (HEXA protein, human); EC 3.2.1.52 (beta-Hexosaminidase alpha Chain); EC 3.2.1.76 (IDUA protein, human); EC 3.2.1.76 (Iduronidase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.05.096


  8 / 1351 MEDLINE  
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[PMID]:28872463
[Au] Autor:Bartolomeo R; Cinque L; De Leonibus C; Forrester A; Salzano AC; Monfregola J; De Gennaro E; Nusco E; Azario I; Lanzara C; Serafini M; Levine B; Ballabio A; Settembre C
[Ad] Endereço:Telethon Institute of Genetics and Medicine (TIGEM), and.
[Ti] Título:mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy.
[So] Source:J Clin Invest;127(10):3717-3729, 2017 Oct 02.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The mammalian target of rapamycin complex 1 (mTORC1) kinase promotes cell growth by activating biosynthetic pathways and suppressing catabolic pathways, particularly that of macroautophagy. A prerequisite for mTORC1 activation is its translocation to the lysosomal surface. Deregulation of mTORC1 has been associated with the pathogenesis of several diseases, but its role in skeletal disorders is largely unknown. Here, we show that enhanced mTORC1 signaling arrests bone growth in lysosomal storage disorders (LSDs). We found that lysosomal dysfunction induces a constitutive lysosomal association and consequent activation of mTORC1 in chondrocytes, the cells devoted to bone elongation. mTORC1 hyperphosphorylates the protein UV radiation resistance-associated gene (UVRAG), reducing the activity of the associated Beclin 1-Vps34 complex and thereby inhibiting phosphoinositide production. Limiting phosphoinositide production leads to a blockage of the autophagy flux in LSD chondrocytes. As a consequence, LSD chondrocytes fail to properly secrete collagens, the main components of the cartilage extracellular matrix. In mouse models of LSD, normalization of mTORC1 signaling or stimulation of the Beclin 1-Vps34-UVRAG complex rescued the autophagy flux, restored collagen levels in cartilage, and ameliorated the bone phenotype. Taken together, these data unveil a role for mTORC1 and autophagy in the pathogenesis of skeletal disorders and suggest potential therapeutic approaches for the treatment of LSDs.
[Mh] Termos MeSH primário: Autofagia
Desenvolvimento Ósseo
Doenças por Armazenamento dos Lisossomos/metabolismo
Complexos Multiproteicos/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Animais
Beclina-1/genética
Beclina-1/metabolismo
Condrócitos/metabolismo
Condrócitos/patologia
Doenças por Armazenamento dos Lisossomos/genética
Doenças por Armazenamento dos Lisossomos/patologia
Alvo Mecanístico do Complexo 1 de Rapamicina
Camundongos
Camundongos Knockout
Complexos Multiproteicos/genética
Fosfatidilinositóis/genética
Fosfatidilinositóis/metabolismo
Fosforilação/genética
Fosforilação/efeitos da radiação
Serina-Treonina Quinases TOR/genética
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Beclin-1); 0 (Becn1 protein, mouse); 0 (Multiprotein Complexes); 0 (Phosphatidylinositols); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171118
[Lr] Data última revisão:
171118
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE


  9 / 1351 MEDLINE  
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[PMID]:28734840
[Au] Autor:Fratz-Berilla EJ; Ketcham SA; Parhiz H; Ashraf M; Madhavarao CN
[Ad] Endereço:Division of Product Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
[Ti] Título:An improved purification method for the lysosomal storage disease protein ß-glucuronidase produced in CHO cells.
[So] Source:Protein Expr Purif;140:28-35, 2017 Dec.
[Is] ISSN:1096-0279
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human ß-glucuronidase (GUS; EC 3.2.1.31) is a lysosomal enzyme that catalyzes the hydrolysis of ß-d-glucuronic acid residues from the non-reducing termini of glycosaminoglycans. Impairment in GUS function leads to the metabolic disorder mucopolysaccharidosis type VII, also known as Sly syndrome. We produced GUS from a CHO cell line grown in suspension in a 15 L perfused bioreactor and developed a three step purification procedure that yields ∼99% pure enzyme with a recovery of more than 40%. The method can be completed in two days and has the potential to be integrated into a continuous manufacturing scheme.
[Mh] Termos MeSH primário: Glucuronidase/biossíntese
Glucuronidase/isolamento & purificação
Doenças por Armazenamento dos Lisossomos/enzimologia
[Mh] Termos MeSH secundário: Animais
Células CHO/enzimologia
Cricetulus
Glucuronidase/química
Seres Humanos
Doenças por Armazenamento dos Lisossomos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.2.1.31 (Glucuronidase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE


  10 / 1351 MEDLINE  
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[PMID]:28428354
[Au] Autor:Liu Y; Yi F; Kumar AB; Kumar Chennamaneni N; Hong X; Scott CR; Gelb MH; Turecek F
[Ad] Endereço:Departments of Chemistry.
[Ti] Título:Multiplex Tandem Mass Spectrometry Enzymatic Activity Assay for Newborn Screening of the Mucopolysaccharidoses and Type 2 Neuronal Ceroid Lipofuscinosis.
[So] Source:Clin Chem;63(6):1118-1126, 2017 Jun.
[Is] ISSN:1530-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We expanded the use of tandem mass spectrometry combined with liquid chromatography (LC-MS/MS) for multiplex newborn screening of seven lysosomal enzymes in dried blood spots (DBS). The new assays are for enzymes responsible for the mucopolysaccharidoses (MPS-I, -II, -IIIB, -IVA, -VI, and -VII) and type 2 neuronal ceroid lipofuscinosis (LINCL). METHODS: New substrates were prepared and characterized for tripeptidyl peptidase 1 (TPP1), α- -acetylglucosaminidase (NAGLU), and lysosomal ß-glucuronidase (GUSB). These assays were combined with previously developed assays to provide a multiplex LC-MS/MS assay of 7 lysosomal storage diseases. Multiple reaction monitoring of ion dissociations for enzyme products and deuterium-labeled internal standards was used to quantify the enzyme activities. RESULTS: Deidentified DBS samples from 62 nonaffected newborns were analyzed to simultaneously determine (run time 2 min per DBS) the activities of TPP1, NAGLU, and GUSB, along with those for α-iduronidase (IDUA), iduronate-2-sulfatase (I2S), -acetylgalactosamine-6-sulfatase (GALNS), and -acetylgalactosamine-4-sulfatase (ARSB). The activities measured in the 7-plex format showed assay response-to-blank-activity ratios (analytical ranges) of 102-909 that clearly separated healthy infants from affected children. CONCLUSIONS: The new multiplex assay provides a robust comprehensive newborn screening assay for the mucopolysaccharidoses. The method has been expanded to include additional lysosomal storage diseases.
[Mh] Termos MeSH primário: Teste em Amostras de Sangue Seco/métodos
Doenças por Armazenamento dos Lisossomos/enzimologia
Mucopolissacaridoses/metabolismo
Triagem Neonatal/métodos
Lipofuscinoses Ceroides Neuronais/enzimologia
[Mh] Termos MeSH secundário: Cromatografia Líquida
Seres Humanos
Recém-Nascido
Doenças por Armazenamento dos Lisossomos/sangue
Doenças por Armazenamento dos Lisossomos/diagnóstico
Mucopolissacaridoses/sangue
Lipofuscinoses Ceroides Neuronais/sangue
Lipofuscinoses Ceroides Neuronais/diagnóstico
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.1373/clinchem.2016.269167



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