Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three to nine days after administration of suramin, 500 mg/kg intravenously in rats, a small amount of the drug (about 0.25 micromoles/g tissue) was retained by the liver and spleen, and a larger amount (about 1.2 micromoles/g tissue) was retained by the kidneys. The activities of the sphingolipid hydrolases beta-hexosaminidase and GM3-sialidase were strongly inhibited by suramin in vitro. The activity of beta-hexosaminidase was inhibited 70% by 10(-5M) and 85% by 10(-4M) suramin, and the activity of GM3-sialidase was inhibited 80% by 10(-4M) suramin. The activities of sphingomyelinase and beta-galactosidase were also inhibited by suramin but at higher concentrations of the drug. Suramin, in vitro is a weak inhibitor of glucocerebrosidase, galactocerebrosidase, alpha-galactosidase and arylsulfatase A (less than 50% inhibition at 10(-3M) concentration of the drug). The inhibition of beta-hexosaminidase by suramin was non-competitive. Inhibition of beta-hexosaminidase and GM3-sialidase may explain the accumulation of GM2 and GM3 gangliosides in the brains of rats treated intracerebrally with suramin (Constantopoulos et al, 1980).
 ...
PMID:Effect of suramin on the activities of degradative enzymes of sphingolipids in rats. 729 29

We have constructed two recombinant adeno-associated virus (AAV) vectors (pJJ-3GC and pJJ-3ASA) which contained either the human glucocerebrosidase (GC) or arylsulfatase A (ASA) cDNA under the control of an SV40 promoter. These plasmids were co-transfected to 293 cells with a helper plasmid containing trans-acting AAV genes required for packaging the vectors. The two recombinant vectors successfully infected murine and patient fibroblasts. The human glucocerebrosidase and arylsulfatase A genes were expressed at high levels in the cells as determined by Western blot analysis, enzyme assay and immunochemical staining. GC enzyme activity in Gaucher patient fibroblasts (GM-0877) infected by AAV-GC was 15-fold higher than in non-infected cells. ASA enzyme activity in MLD 557g cells infected by AAV-ASA was up to 500-fold higher than in the metachromatic leukodystrophy (MLD) control cells. Southern blotting results showed that the vector integrated 1-2 copies of pJJ-3GC and ASA in the targeted cell genome. These two vectors will be useful in studying AAV-mediated transfer of the GC and ASA genes in cells and animals.
 ...
PMID:Expression of the human glucocerebrosidase and arylsulfatase A genes in murine and patient primary fibroblasts transduced by an adeno-associated virus vector. 758 90

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of a patient affected with late infantile metachromatic leukodystrophy revealed that the patient is a compound heterozygote of two alleles carrying two deleterious mutation each. One allele bears a splice donor site mutation together with two polymorphisms and an additional missense mutation (Gly122 > Ser). The splice donor site mutation and the Gly122 > Ser substitution have been described recently but on different alleles. The other allele carries two missense mutations causing a Gly154 > Asp and a Pro167 > Arg substitution. When arylsulfatase A cDNAs carrying these mutations separately or in combination were transfected into baby hamster kidney cells expression of arylsulfatase A activity could not be detected. Linkage of mutations was verified by sequencing of the parental DNAs. Biosynthesis studies performed with the patients' fibroblasts show that the enzyme carrying both mutations is synthesized in almost normal amounts but is rapidly degraded in an early biosynthetic compartment. The occurence of two disease causing mutations on the same allele is a novel phenomenon in metachromatic leukodystrophy and as far as lysosomal storage diseases are concerned have so far only been described in Fabry disease and in the complex glucocerebrosidase alleles associated with Gaucher disease.
 ...
PMID:Complex arylsulfatase A alleles causing metachromatic leukodystrophy. 798 15

The characterization of mutations in Japanese patients with lipidosis, particularly in metachromatic leukodystrophy (MLD) and Gaucher disease has been studied in detail. Metachromatic leukodystrophy is characterized by an accumulation of sulfatide in nervous tissues and kidney due to a deficiency of arylsulfatase A (ASA). We analyzed the presence of three known mutant arylsulfatase A alleles in Japanese patients with MLD. Among 10 patients of Japanese patients with MLD, we found that allele 445A mutation has moderately high incidence and also homozygosity of this mutation results in the late infantile form. Allele 2381T was not found in Japanese patients. Furthermore, we found novel mutation which is G- to A mutation at the 1070 nucleotide of the ASA gene (designated 1070 A) in Japanese patients with juvenile onset. This mutation results in a amino acid substitution of Gly245 by Arg and found in heterozygote form. Our studies of molecular analysis in 10 Japanese patients with MLD indicate that Japanese MLD patients have unique characteristics of ASA mutations compared with those of Caucasian patients. On the other hand, Gaucher disease is the most prevalent sphingolipidosis, characterized by an accumulation of glucocerebroside in macrophage derived cells due to a deficiency of lysosomal hydrolase glucocerebrosidase. To study the molecular basis of Gaucher disease in Japanese patients, we analyzed the presence of the two known mutations (6433C and 3548A) in the glucocerebrosidase gene of 15 patients with Gaucher disease. We found that the 6433C and 3548A mutations occur in all subtypes of Japanese patients with Gaucher disease.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Molecular characteristics in Japanese patients with lipidosis: novel mutations in metachromatic leukodystrophy and Gaucher disease. 845 80

Human bone marrow contains mesenchymal stem cells (MSCs) that can differentiate into various cells of mesenchymal origin. We developed an efficient method of isolating and culture expanding a homogenous population of MSCs from bone marrow and determined that MSCs express alpha-L-iduronidase, arylsulfatase-A and B, glucocerebrosidase, and adrenoleukodystrophy protein. These findings raised the possibility that MSCs may be useful in the treatment of storage disorders. To determine if donor derived MSCs are transferred to the recipients with lysosomal or peroxisomal storage diseases by allogeneic hematopoietic stem cell (HSC) transplantation, we investigated bone marrow derived MSCs of 13 patients 1-14 years after allogeneic transplantation. Highly purified MSCs were genotyped either by fluorescence in situ hybridization using probes for X and Y-chromosomes in gender mis-matched recipients or by radiolabeled PCR amplification of polymorphic simple sequence repeats. Phenotype was determined by the measurement of disease specific protein/enzyme activity in purified MSCs. We found that MSCs isolated from recipients of allogeneic HSC transplantation are not of donor genotype and have persistent phenotypic defects despite successful donor type hematopoietic engraftment. Whether culture expanded normal MSCs can be successfully transplanted into patients with storage diseases and provide therapeutic benefit needs to be determined.
 ...
PMID:Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases. 1056 Sep 15