Increased O-GlcNAc causes disrupted lens fiber cell differentiation and cataracts

Kai Wang, Shiuh Rong Ho, Weiming Mao, Ping Huang, Fengxue Zhang, Erik M. Schwiebert, Jeffrey E. Kudlow, Andrew J. Paterson

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Diminished proteolytic functionality in the lens may cause cataracts. We have reported that O-GlcNAc is an endogenous inhibitor of the proteasome. We hypothesize that in the lens there is a cause-and-effect relationship between proteasome inhibition by O-GlcNAc, and cataract formation. To demonstrate this, we established novel transgenic mouse models to over-express a dominant-negative form of O-GlcNAcase, GK-NCOAT, in the lens. Expression of GK-NCOAT suppresses removal of O-GlcNAc from proteins, resulting in increased levels of O-GlcNAc in the lenses of our transgenic mice, along with decreased proteasome function. We observed that transgenic mice developed markedly larger cataracts than controls and lens fiber cell denucleation was inhibited. Our study suggests that increased O-GlcNAc in the lens could lead to cataract formation and attenuation of lens fiber cell denucleation by inhibition of proteasome function. These findings may explain why cataract formation is a common complication of diabetes since O-GlcNAc is derived from glucose.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume387
Issue number1
DOIs
StatePublished - Sep 11 2009
Externally publishedYes

Keywords

  • Diabetes
  • Glycosylation
  • NCOAT
  • Proteasome
  • Transgenic mice

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Wang, K., Ho, S. R., Mao, W., Huang, P., Zhang, F., Schwiebert, E. M., Kudlow, J. E., & Paterson, A. J. (2009). Increased O-GlcNAc causes disrupted lens fiber cell differentiation and cataracts. Biochemical and Biophysical Research Communications, 387(1), 70-76. https://doi.org/10.1016/j.bbrc.2009.06.132