Purification and some properties of arylsulphatases A and B from rabbit kidney cortex.
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Arylsulphatases A and B (EC 3.1.6.1) of rabbit kidney cortex were purified 5250- and 7720-fold respectively by a multiple-column-chromatography method. The specific activity toward 4-nitrocatechol sulphate was 42mumol/min per mg for arylsulphatase A and 62 mumol/min per mg for arylsulphatase B. Each enzyme migrated as a single band on polyacrylamide-gel electrophoresis, and the enzyme activity corresponded to the band of protein on the gel. The rate of hydrolysis of ascorbic acid 2-sulphate by arylsulphatase A was three times that for cerebroside 3-sulphate. Arylsulphatase B hydrolysed UDP-N--acetylgalactosamine 4-sulphate and glucosamine 4,6-disulphate, but not galactosamine 6-sulphate. (+info)
Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy.
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Insulin-like growth factors I and II stimulate endocytosis but do not affect sorting of lysosomal enzymes in human fibroblasts.
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The mannose 6-phosphate (Man-6-P)/insulin-like growth factor (IGF) II receptor has separate binding sites for Man-6-P and IGF II. It targets newly synthesized lysosomal enzymes from the Golgi to acidic pre-lysosomal organelles and mediates endocytosis of Man-6-P-containing ligands and IGF II. The two classes of ligands, Man-6-P and IGF II, as well as IGF I and the epidermal growth factor, induce in fibroblasts a transient redistribution of the receptor from internal membranes to the cell surface (Braulke, T., Tippmer, S., Neher, E., and von Figura, K. (1989) EMBO J. 8, 681-686). Here we show that the redistribution induced by IGF I and IGF II is accomplished without affecting the internalization rate of cell surface receptors. The redistribution results in an increased binding of ligands to the Man-6-P- and IGF II-binding sites of the receptor. Furthermore, the uptake of the lysosomal enzyme arylsulfatase A and of a Man-6-P neoglycoprotein is stimulated 2-3-fold by IGF I and IGF II, and this effect persists for at least 6 h. The IGF I- and IGF II-induced receptor redistribution does not affect the targeting of newly synthesized lysosomal enzymes. These results show that important functions of the Man-6-P/IGF II receptor such as binding and internalization of ligands can be up-regulated by the ligands of this receptor and other growth factors such as IGF I through redistribution of the receptor. (+info)
Compensatory expression of human N-acetylglucosaminyl-1-phosphotransferase subunits in mucolipidosis type III gamma.
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A 14-kb genomic clone containing the entire gene of human lysosomal arylsulfatase A was isolated. The arylsulfatase A gene is about 3.2 kb long and has eight exons (103-320 nucleotides in size). All intron-exon splice junctions conformed to the GT/AG consensus sequence. S1 nuclease mapping shows multiple transcription initiation sites between nucleotides -367 and -387. A fragment encompassing 360 nucleotides of the flanking sequence upstream of the transcription initiation site shows promoter activity when it was transiently expressed in COS cells using the gene for bacterial chloramphenicol acetyltransferase as a reporter gene. This putative promoter region shows four potential Sp1 binding sites but lacks typical TATA and CAAT box sequences. Three different mRNA species of 2.1, 3.7 and 4.8 kb are transcribed from the gene and arise probably from the use of different polyadenylation signals. (+info)
Adult metachromatic leukodystrophy without deficiency of arylsulphatase.
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An adult case of metachromatic leukodystrophy, proved by characteristic findings of the brain and superficial sural nerve biopsies, but with absence of deficiency of arylsulphatase A activity in the leucocytes, was reported. The long course of thirty years, the absence of deficiency of arylsulphatase A activity, the discrepancy between the normal conduction velocity of the peripheral nerves and the typical pathological findings of the superficial sural nerve under the light and electron microscopes and the significance of the diffuse hypodense areas and high intensity signals of the cerebral white matter on CT and MRI respectively, were discussed. (+info)
Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate.
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