Metabolism of Macromolecular Heparin in Murine Neoplastic Mast Cells

Ögren, S.O.; Lindahl, Ulf

doi:10.1007/978-1-4684-0946-8_6

Cited by 17 publications

(23 citation statements)

References 10 publications

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“…In the mouse mastocytoma, biosynthesis and degradation of the macromolecular heparin occur in rapid succession (Ogren & Lindahl, 1971; S. Ogren & U. Lindahl, unpublished work); it has been suggested by Homer (1972) that the degradation process may be required to convert the heparin into its physiologically active form. The enzyme responsible for the degradation ofmacromolecular heparin in mouse mastocytoma has been isolated and tentatively identified as an endoglucuronidase (Ogren & Lindahl, 1975). These findings, in conjunction with the results of the present study, suggest that formation and degradation of macromolecular heparin may occur also in mammals other than rodents (see also Homer, 1970).…”

Section: Macromolecular Properties Of Heparin and Dermatan Sulphate Fsupporting

confidence: 82%

“…Results of model experiments to be reported elsewhere Ogren & Lindahl, 1975) demonstrated that a glucuronic acid residue in the reducible terminal position of a polysaccharide chain was in fact recovered as [3H] gulonic acid by the procedure employed. Glucosamine residues in a similar position were largely converted into an uncharged, labelled deamination product; a smaller fraction appeared as a component instead having terminal, reducible uronic acid residues.…”

Section: Macromolecular Properties Of Heparin and Dermatan Sulphate Fmentioning

confidence: 83%

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Macromolecular properties and end-group analysis of heparin isolated from bovine liver capsule

Jansson¹,

Ogren²,

Lindahl³

1975

Biochemical Journal

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Glycosaminoglycans were extracted from bovine liver capsule with 4M-guanidinium chloride, resulting in solubilization of approx. 90% of the total uronic acid-containing polysaccharide of the tissue. The extracted polysaccharide was purified and fractionated by anion-exchange chromatography on DEAE-cellulose, density-gradient ultracentrifugation in CsCl and finally gel chromatography on Sepharose 4B. By using these procedures, the two major polysaccharide components, dermatan sulphate and heparin, which constituted 55 and 30 % respectively of the total glycosaminoglycan content of the tissue, were separated from each other. Analysis of the macromolecular properties of the two polysaccharides showed that heparin existed exclusively as single polysaccharide chains, whereas dermatan sulphate occurred largely as a proteoglycan (protein content, 74% dry wt.). The purified heparin preparation was subjected to sedimentationequilibrium ultracentrifugation, indicating a molecular weight of 8800. Analysis for neutral sugars (by g.l.c.) showed 0.1 residue of xylose and 0.2 residue of galactose/ polysaccharide chain; serine amounted to 0.3 residue/polysaccharide chain. Reduction of the heparin with NaB3H4 resulted in incorporation of 3H, approximately corresponding to one reducible group/polysaccharide chain. The 3H-labelled sugar residue was liberated by a combination of acid hydrolysis and deaminative cleavage of the polysaccharide with HNO2; it was subsequently identified as an aldonic acid by paper electrophoresis. Most of the heparin chains thus contained a uronic acid residue in reducing position. It is suggested that heparin isolated from bovine liver capsule is a degradation product released from larger molecules by an endo-glycuronidase.

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Section: Macromolecular Properties Of Heparin and Dermatan Sulphate Fsupporting

confidence: 82%

Section: Macromolecular Properties Of Heparin and Dermatan Sulphate Fmentioning

confidence: 83%

Macromolecular properties and end-group analysis of heparin isolated from bovine liver capsule

Jansson¹,

Ogren²,

Lindahl³

1975

Biochemical Journal

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“…The saccharides were reduced with NaB[3H]4 (New England Nu- Cell Culture. Fibroblasts from the skin of normal individuals or patients affected with mucopolysaccharidoses were maintained in culture as described (25 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) ,g of cell protein) and 220 pmol of substrate (11,000 cpm) in 50 mM NaOAc, pH 4.0/0.02% NaN3/0.0015% bovine serum albumin in a final volume of 10Ml. Incubation was for 3-6 hr at 370C.…”

Section: Methodsmentioning

confidence: 99%

“…The hydrolysis of p-NP-GlcNAc(6S) was followed by incubation of [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] ,B-glucuronidase (20), and ,B-N-acetylglucosaminidase (20)-were measured as described. Glucosamine, galactose, sulfate, and protein were determined as described (28).…”

Section: Methodsmentioning

confidence: 99%

Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

Kresse¹,

Paschke²,

Figura³

et al. 1980

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

102

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Skin fibroblasts from two patients who had symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated excessive amounts of hean sulfate and were unable to release sulfate from N-acety lucosamine)--sulfate linkages in heparan sulfate-derived oligosaccharides. Keratan sulfate-derived oligosaccharides bearing the same residue at the nonreducing end and p-nitrophenyl6sulfo-2-acetamido-2-deoxy-D-ucopyranoside were degraded normally. Kinetic differences between the sulfatase activities of normal fibroblasts were found. These observations suggest that N-acetylglucosamine4-6sulfate sulfatase activities degrading heparan sulfate and keratan sulfate, respectively, can be distinguished.

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“…Heparanases have been found in various cells and tissues, including human platelets (14,15), placenta (16), mouse mastocytoma (17,18), colon carcinoma (19), mouse melanoma (20), rat liver (21), hepatocytes (9), rat ovarian granulosa cells (10), and CHO 1 cells (6,7). As endo-␤-glucuronidases, the enzymes produce oligosaccharides with GlcUA at their reducing ends (6,14,22) and a glucosamine residue at their nonreducing ends.…”

mentioning

confidence: 99%

Turnover of Heparan Sulfate Depends on 2-O-Sulfation of Uronic Acids

Bai

Bame²,

Habuchi³

et al. 1997

Journal of Biological Chemistry

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To study how the pattern of sulfation along a heparan sulfate chain affects its turnover, we examined heparan sulfate catabolism in wild-type Chinese hamster ovary cells and mutant pgsF-17, defective in 2-O-sulfation of uronic acid residues (Bai, X., and Esko, J. D. (1996) J. Biol. Chem. 271, 17711-17717). Heparan sulfate from the mutant contains normal amounts of 6-O-sulfated glucosamine residues and iduronic acid and somewhat higher levels of N-sulfated glucosamine residues but lacks any 2-O-sulfated iduronic or glucuronic acid residues. Pulse-chase experiments showed that both mutant and wild-type cells transport newly synthesized heparan sulfate proteoglycans to the plasma membrane, where they shed into the medium or move into the cell through endocytosis. Internalization of the cell-associated molecules leads to sequential endoglycosidase (heparanase) fragmentation of the chains and eventual lysosomal degradation. In wild-type cells, the chains begin to degrade within 1 h, leading to the accumulation of intermediate (10 -20-kDa) and small (4 -7-kDa) oligosaccharides. Mutant cells did not generate these intermediates, although internalization and intracellular trafficking of the heparan sulfate chains appeared normal, and the chains degraded with normal kinetics. This difference was not due to defective heparanase activities in the mutant, since cytoplasmic extracts from mutant cells cleaved wild-type heparan sulfate chains in vitro. Instead, the heparan sulfate chains from the mutant were relatively resistant to degradation by cellular heparanases. These findings suggest that 2-O-sulfated iduronic acid residues in heparan sulfate are important for cleavage by endogenous heparanases but not for the overall catabolism of the chains.

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Metabolism of Macromolecular Heparin in Murine Neoplastic Mast Cells

Cited by 17 publications

References 10 publications

Macromolecular properties and end-group analysis of heparin isolated from bovine liver capsule

Macromolecular properties and end-group analysis of heparin isolated from bovine liver capsule

Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

Turnover of Heparan Sulfate Depends on 2-O-Sulfation of Uronic Acids

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