Defective processing of keratan sulfate in Macular corneal dystrophy

Research output: Contribution to journalArticle

Standard

Defective processing of keratan sulfate in Macular corneal dystrophy. / Nakazawa, K.; Hassell, J. R.; Hascall, V. C.; Lohmander, Stefan; Newsome, D. A.; Krachmer, J.

In: Journal of Biological Chemistry, Vol. 259, No. 22, 1984, p. 13751-13757.

Research output: Contribution to journalArticle

Harvard

Nakazawa, K, Hassell, JR, Hascall, VC, Lohmander, S, Newsome, DA & Krachmer, J 1984, 'Defective processing of keratan sulfate in Macular corneal dystrophy', Journal of Biological Chemistry, vol. 259, no. 22, pp. 13751-13757.

APA

Nakazawa, K., Hassell, J. R., Hascall, V. C., Lohmander, S., Newsome, D. A., & Krachmer, J. (1984). Defective processing of keratan sulfate in Macular corneal dystrophy. Journal of Biological Chemistry, 259(22), 13751-13757.

CBE

Nakazawa K, Hassell JR, Hascall VC, Lohmander S, Newsome DA, Krachmer J. 1984. Defective processing of keratan sulfate in Macular corneal dystrophy. Journal of Biological Chemistry. 259(22):13751-13757.

MLA

Vancouver

Nakazawa K, Hassell JR, Hascall VC, Lohmander S, Newsome DA, Krachmer J. Defective processing of keratan sulfate in Macular corneal dystrophy. Journal of Biological Chemistry. 1984;259(22):13751-13757.

Author

Nakazawa, K. ; Hassell, J. R. ; Hascall, V. C. ; Lohmander, Stefan ; Newsome, D. A. ; Krachmer, J. / Defective processing of keratan sulfate in Macular corneal dystrophy. In: Journal of Biological Chemistry. 1984 ; Vol. 259, No. 22. pp. 13751-13757.

RIS

TY - JOUR

T1 - Defective processing of keratan sulfate in Macular corneal dystrophy

AU - Nakazawa, K.

AU - Hassell, J. R.

AU - Hascall, V. C.

AU - Lohmander, Stefan

AU - Newsome, D. A.

AU - Krachmer, J.

PY - 1984

Y1 - 1984

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0021685042&partnerID=8YFLogxK

M3 - Article

VL - 259

SP - 13751

EP - 13757

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 22

ER -