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Defective processing of keratan sulfate in Macular corneal dystrophy

Nakazawa, K.; Hassell, J. R.; Hascall, V. C.; Lohmander, Stefan LU ; Newsome, D. A. and Krachmer, J. (1984) In Journal of Biological Chemistry 259(22). p.13751-13757
Abstract

macular corneal dystrophy is a human genetic disorder characterized by corneal opacities that arise, in part, from a failure to synthesize mature keratan sulfate proteoglycans. The macromolecules in macular corneas and in keratoconus corneas, an abnormality not involving proteoglycans, were biosynthetically labeled with [3H]mannose and [14C]glucosamine in organ culture, and the keratan sulfate proteoglycans were immunoprecipitated with antibodies against the protein core of monkey keratan sulfate proteoglycan. The chondroitin sulfate proteoglycans, which did not react with the antibody, were oversulfated in corneas from patients with macular corneal dystrophy. Characterization of the immunoprecipitates showed that... (More)

macular corneal dystrophy is a human genetic disorder characterized by corneal opacities that arise, in part, from a failure to synthesize mature keratan sulfate proteoglycans. The macromolecules in macular corneas and in keratoconus corneas, an abnormality not involving proteoglycans, were biosynthetically labeled with [3H]mannose and [14C]glucosamine in organ culture, and the keratan sulfate proteoglycans were immunoprecipitated with antibodies against the protein core of monkey keratan sulfate proteoglycan. The chondroitin sulfate proteoglycans, which did not react with the antibody, were oversulfated in corneas from patients with macular corneal dystrophy. Characterization of the immunoprecipitates showed that macular corneas did not make keratan sulfate proteoglycan but did synthesize an immunoreactive glycoprotein in nearly equal amounts as keratan sulfate proteoglycan was synthesized by the keratoconus cornea. The oligosaccharides on the immunoprecipitated macular glycoprotein appeared to be normal. However, the macromolecules contained an unsulfated glycoconjugate that was nearly as large as the normal keratan sulfate chains isolated from the keratoconus keratan sulfate-proteoglycan and contained the same relative proportions of labeled glucosamine, mannose, and fucose. This glycoconjugate was resistant to digestion with keratanase. These observations indicate that macular corneal dystropy is caused by an error in the synthesis of keratan sulfate, possibly involving the specific sulfotransferases involved in sulfation of the lactosaminoglycan backbone of the chains.

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published
in
Journal of Biological Chemistry
volume
259
issue
22
pages
7 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • Scopus:0021685042
ISSN
0021-9258
language
English
LU publication?
yes
id
89447ea0-0143-4e41-97be-daac1280532b
date added to LUP
2016-05-04 12:56:37
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2016-08-02 16:11:51
@misc{89447ea0-0143-4e41-97be-daac1280532b,
  abstract     = {<p>macular corneal dystrophy is a human genetic disorder characterized by corneal opacities that arise, in part, from a failure to synthesize mature keratan sulfate proteoglycans. The macromolecules in macular corneas and in keratoconus corneas, an abnormality not involving proteoglycans, were biosynthetically labeled with [<sup>3</sup>H]mannose and [<sup>14</sup>C]glucosamine in organ culture, and the keratan sulfate proteoglycans were immunoprecipitated with antibodies against the protein core of monkey keratan sulfate proteoglycan. The chondroitin sulfate proteoglycans, which did not react with the antibody, were oversulfated in corneas from patients with macular corneal dystrophy. Characterization of the immunoprecipitates showed that macular corneas did not make keratan sulfate proteoglycan but did synthesize an immunoreactive glycoprotein in nearly equal amounts as keratan sulfate proteoglycan was synthesized by the keratoconus cornea. The oligosaccharides on the immunoprecipitated macular glycoprotein appeared to be normal. However, the macromolecules contained an unsulfated glycoconjugate that was nearly as large as the normal keratan sulfate chains isolated from the keratoconus keratan sulfate-proteoglycan and contained the same relative proportions of labeled glucosamine, mannose, and fucose. This glycoconjugate was resistant to digestion with keratanase. These observations indicate that macular corneal dystropy is caused by an error in the synthesis of keratan sulfate, possibly involving the specific sulfotransferases involved in sulfation of the lactosaminoglycan backbone of the chains.</p>},
  author       = {Nakazawa, K. and Hassell, J. R. and Hascall, V. C. and Lohmander, Stefan and Newsome, D. A. and Krachmer, J.},
  issn         = {0021-9258},
  language     = {eng},
  number       = {22},
  pages        = {13751--13757},
  publisher    = {ARRAY(0x975bdb8)},
  series       = {Journal of Biological Chemistry},
  title        = {Defective processing of keratan sulfate in Macular corneal dystrophy},
  volume       = {259},
  year         = {1984},
}