Lysosomal arylsulfatase deficiencies in humans: Chromosome assignments for arylsulfatase A and B

DeLuca, Chester; Brown, J. Anne; Shows, Thomas B.

doi:10.1073/pnas.76.4.1957

Cited by 41 publications

(10 citation statements)

References 29 publications

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“…The Chinese hamster lines used were CHW-1102 (hypoxanthine phosphoribosyltransferase deficient) maintained on Dulbecco's modified Eagle's medium with 10% fetal calf serum. Fresh human leukocytes used for fusion were prepared as described (8).…”

Section: Methodsmentioning

confidence: 99%

Chromosomal assignment of the gene for the human beta 2-adrenergic receptor.

Sheppard¹,

Wehner²,

McSwigan³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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Chinese hamster fibroblasts (CHW) fail to physiologically respond to the (-adrenergic agonist isoproterenol with an increase in cellular cAMP. This unresponsiveness is due to a lack of (3-adrenergic receptors as indicated by an absence of specific binding of '25I-labeled hydroxybenzylpindolol (125I-HYP) to CHW plasma membranes. Preparation of somatic cell hybrids between CHW and human peripheral blood leukocytes led to the selection of a panel of 15 human-Chinese hamster cell hybrid clones, some of which had P2-adrenergic receptors (specifically bound '25I-HYP) and responded to isoproterenol (accumulated cAMP). Biochemical analysis of independent cloned cell hybrids indicated that (32-adrenergic receptor density and the intensity of the associated physiological response were closely correlated (r = 0.98). Both of these parameters were concordant in all cell hybrids with the presence ofhuman chromosome 5. All other human chromosomes could be ruled out. These results suggest that the structural gene for the fi2-adrenergic receptor is found on human chromosome 5. (6,7). In an effort to examine pharmacogenetic aspects of ,3-adrenergic receptors, human-Chinese hamster cell hybrids were examined and it was observed that some of the hamster-human hybrid clones possessed 83-adrenergic receptors, were also sensitive to /3-adrenergic agonists, and exhibited characteristics ofthe ,B2 subtype. The random and preferential loss of human chromosomes from these hybrids allowed us to identify the human chromosome upon which the human P32-adrenergic gene was located. By examining the expression of specific human isozyme markers as an indication of specific human chromosomes, we demonstrate here that the structural gene for the human 82-adrenergic receptor is located on human chromosome 5. MATERIALS AND METHODSParental Cells and Hybrids. The Chinese hamster lines used were CHW-1102 (hypoxanthine phosphoribosyltransferase deficient) maintained on Dulbecco's modified Eagle's medium with 10% fetal calf serum. Fresh human leukocytes used for fusion were prepared as described (8).Human and Chinese hamster cells were fused, cloned, and maintained on hypoxanthine/aminopterin/thymidine (HAT) selection medium in Dulbecco's modified Eagle's medium with 10% fetal calf serum (8, 9). A total of 15 hybrids were examined for ,&adrenergic receptors and response. They were designated CDC as previously noted (8). ,B-Adrenergic Receptors. 3-Adrenergic receptors were measured in the hamster-human hybrids with the f3-adrenergic antagonist "2I-labeled hydroxybenzylpindolol ('25I-HYP) according to the methods of Sporn and Molinoff (10). Cells were washed twice with phosphate-buffered saline containing Ca2+ and Mg2' and scraped in phosphate-buffered saline. The preparation was swollen in 10 mM Tris HCl, pH 7.3, at 4°C for 20 min and homogenized with seven strokes ofa Teflon-glass Polyscience model RZR10 homogenizer at setting 10. The homogenate was centrifuged for 5 min at 900 X g and the supernatant was centrifuged for 20 min at 11,500 X g. ...

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Section: Methodsmentioning

confidence: 99%

Chromosomal assignment of the gene for the human beta 2-adrenergic receptor.

Sheppard¹,

Wehner²,

McSwigan³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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“…Of interest is that affected enzymes in this disorder are produced by both autosomal and X-linked chromosomes. Arylsulfatases A and B and heparin N-sulfatase are known to be localized in autosomal genes (arylsulfatase A in chromosome number 22 (6) and B in chromosome number 5) (6), whereas arylsulfatase C, cholesterol sulfatase, other steroid sulfatase and sulfoiduronate sulfatase are considered to be localized in X-chromosomes (steroid sulfatase in Xg locus) (17). Most recently, cell fusion studies in which MSD cells were fused with other sulfatase deficient disorder such as MLD, Maroteaux-Lamy syndrome, Sanfilippo A, steroid sulfatase deficient disorder and Hunter syndrome support the hypothesis than an enzyme deficiency in MSD is different from that causing specific sulfatase deficiencies (5,14).…”

Section: Discussionmentioning

confidence: 99%

Various Sulfatase Activities in Leukocytes and Cultured Skin Fibroblasts from Heterozygotes for the Multiple Sulfatase Deficiency (Mukosulfatidosis)

et al. 1983

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SummaryIn heterozygotes for multiple sulfatase deficiency (MSD), several sulfatase activities including arylsulfatases A, BI, B2, and C, and cholesterol sulfatase were 40-50% of normals in cultured skin fibroblasts and 70-80% of normals in leukocytes. In MSD patients, these enzyme activities were deficient or reduced. DEAE-Sepharose column chromatographic patterns of 4-methylumbelliferyl sulfatases A, B1, and B2 in leukocytes and cultured skin fibroblasts from MSD patients and heterozygotes were also consistent with the above data. These data indicate that several sulfatase activities in heterozygotes of MSD exhibited intermediate activities as observed in the heterozygote state of other autosomal recessive inherited diseases.MSD, and a MSD obligate heterozygote (mother). Three different cell cultures of MSD proband were kindly obtained from Prof. H. Kihara (University of California, Pomona USA). Two MSD probands (GM 3245 and GM 2407) and two MSD heterozygote cell cultures (GM 2644 and GM 2667) were shipped from the Human Genetic Cell Repository, Camden, NJ. The cultures were grown under conditions described previously (7). The leukocyte or fibroblast cells were suspended in 0.05 M Tris-HC1 buffer, pH 7.4 and dialyzed overnight against 0.02 M Tris-HC1 buffer (pH 7.4). The cells were disrupted by sonication for 60 sec at 40 "K" cycles in a Branson sonifier. The homogenates were used for enzyme assays of arylsulfatase C, cholesterol sulfatase, and heparin N-sulfatase. For the determination of other sulfatases (arylsulfatases A and B), the homogenate was centrifuged at 100,000 x g for 30 min and the clear supernatant was used for enzyme assays. AbbreviationsFor the fractionation with DEAE-Sepharose column chromatog-MDS, multiple sulfatase deficiency raphy, the soluble fraction was used. MLD, metachromatic leukodystrophy 4-MU, 4-methylumbelliferylMultiple sulfatase deficiency (MSD) is an autosomal recessive disorder, which is clinically characterized by gargoyl-like appearance, skeletal abnormality, hepatosplenomegaly, and ichthyosis (1, 2). Biochemically, the accumulation of sulfatide, acid mucopolysaccharides, and cholesterol sulfate accompanies deficiencies 300 of arylsulfatases A, B, and C , mucopolysaccharide sulfatases -200 (sulfoiduronate sulfatase, sulfamidase, galactosamine-4-sulfatase, galactosamine-6-sulfatase) and steroid sulfatases (cholesterol sulloo fatase, dehydroepiandrosterone sulfatase, estrone sulfatase, pregnenolone sulfatase) in patients' tissues and cultured skin fibroblasts (1, 2,.3, 7, 18).This disorder is of considerable theoretical interest in genetics, because there are deficient activities of several different enzymes. In terms of the genetic controlling mechanisms of sulfatases, it is important to determine whether sulfatase activities in the heterozygote exhibit intermediate activities.This report demonstrates that various sulfatase activities in heterozygotes were about one-half of controls in cultured skin fibroblasts and 70-80% of controls in leukocytes. In addition, the arylsulfata...

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“…Sandvig and Olsnes (26) reported that diphtheria toxin entry into cells is facilitated by low pH even in the presence m Ó Ó á too Diphtheria toxin warma FIGURE 4 Effect of diphtheria toxin on the rate of protein synthesis of cells after treatment with HVJ . The treatment with HVJ was carried out as described under Materials and Methods .…”

Section: Effect Of Ph On the Sensitivity To Crm 45mentioning

confidence: 99%

“…(27) and Deluca et al . (4) . Chromosomes in each hybrid were identified after 33258 Hoechst-quinacrine mustard staining (33).…”

Section: Association Of Iodinated Diphtheria Toxin With Cellsmentioning

confidence: 99%

Entry of diphtheria toxin into cells: possible existence of cellular factor(s) for entry of diphtheria toxin into cells was studied in somatic cell hybrids and hybrid toxins.

Kaneda¹,

Uchida²,

Mekada³

et al. 1984

The Journal of Cell Biology

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Ehrlich ascites tumor cells were found to be very insensitive to diphtheria toxin . We formed 37 hybrids from Ehrlich tumor cells and diphtheria toxin-sensitive human fibroblasts. The effects of diphtheria toxin on protein synthesis in those hybrids were examined . The hybrids were divided into three groups on the basis of toxin sensitivity . Group A hybrids were as sensitive to diphtheria toxin as human fibroblasts, Group C were as resistant as Ehrlich tumor cells, and Group B had intermediate sensitivity . Group A hybrids had diphtheria toxinbinding sites but Group B and C had no detectable binding sites. Elongation factor-2 of all the hybrids was susceptible to ADP-ribosylation by fragment A of diphtheria toxin . Cells of Group A and B became more sensitive to CRM 45 (cross-reacting material 45 of diphtheria toxin) after they were exposed to low pH (pH = 4.5) . The resistance of Group C to CRM 45 was not affected by the same treatment . Group A and B hybrids and human fibroblasts had similar sensitivities to a hybrid toxin composed of wheat germ agglutinin and fragment A of diphtheria toxin, but Group C and Ehrlich tumor cells were resistant to this hybrid toxin . All the hybrids and Ehrlich tumor cells were more sensitive to a hybrid toxin composed of wheat germ agglutinin and subunit A of ricin than were human fibroblasts . On subcloning of Group B hybrids, one Group C hybrid was obtained, but no Group A hybrid . These facts suggest that Ehrlich ascites tumor cells differ from human fibroblasts in the expression of a factor(s) that is involved in entry of fragment A of diphtheria toxin into the cytoplasm after the toxin binds to its surface receptors .

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Lysosomal arylsulfatase deficiencies in humans: Chromosome assignments for arylsulfatase A and B

Cited by 41 publications

References 29 publications

Chromosomal assignment of the gene for the human beta 2-adrenergic receptor.

Chromosomal assignment of the gene for the human beta 2-adrenergic receptor.

Various Sulfatase Activities in Leukocytes and Cultured Skin Fibroblasts from Heterozygotes for the Multiple Sulfatase Deficiency (Mukosulfatidosis)

Entry of diphtheria toxin into cells: possible existence of cellular factor(s) for entry of diphtheria toxin into cells was studied in somatic cell hybrids and hybrid toxins.

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