PROTEIN CLEAVAGE SITES IN EXPERIMENTAL CATARACTOUS LENSE

Project: Research project

Project Details

Description

Cataracts are the third leading cause of blindness in the United
States. However, the underlying biochemical mechanisms of most
cataracts are unknown. One alteration in lenses that may
contribute to cataract formation is accumulation of partially
degraded protein fragments. Many experimental cataracts studied
to date contain significant amounts of partially degraded lens
proteins. The role these proteins play in cataract formation and
which lens proteases are responsible for protein degradation are
unknown. The two goals of this project are to better understand the
significance of proteolysis in cataractous lenses, and to determine
which endogenous lens proteases are activated during cataract
formation. Partially degraded lens proteins, from selenite and
galactose induced cataracts and rom hereditary mouse cataracts,
will be isolated by electrophoresis. These partially degraded
polypeptides will be analyzed using protein micro-sequencing
techniques to identify their origin, and to determine their N - and
C-terminal cleavage sites. Intact lens proteins will then be
incubated in vitro with three different major lens endopeptidases
(high molecular neutral protease complex, trypsin-like protease,
and calpain II). The cleavage sites occurring in vitro will be
compared to cleavage sites occurring in vivo during cataract
formation. Endopeptidase cleaved lens proteins will also be
incubated with two major lens exopeptidases (aminopeptidase III and
leucine aminopeptidase). This will determine if endopeptidase
cleavage makes lens proteins better substrates for exopeptidases. Proteolysis may contribute to cataract formation by significantly
altering the properties of lens proteins. Comparison of in vivo
cleavage sites found in cataractous lenses with cleavage sites
produced by proteases in vitro may identify the proteases that are
activated in the lens. Determining which lens proteases are active
during experimental cataract formation may suggest ways of treating
human cataract. For instance, inhibitors of proteases could be
used as therapeutic agents to slow the progression of cataract.
StatusFinished
Effective start/end date4/1/897/31/16

Funding

  • National Institutes of Health: $256,452.00
  • National Institutes of Health: $148,706.00
  • National Institutes of Health: $92,500.00
  • National Institutes of Health: $261,685.00
  • National Institutes of Health: $142,490.00
  • National Institutes of Health: $213,750.00
  • National Institutes of Health: $346,500.00
  • National Institutes of Health: $188,750.00
  • National Institutes of Health: $76,016.00
  • National Institutes of Health: $339,570.00
  • National Institutes of Health: $294,382.00
  • National Institutes of Health: $188,750.00
  • National Institutes of Health: $85,595.00
  • National Institutes of Health: $329,175.00
  • National Institutes of Health: $188,750.00
  • National Institutes of Health: $346,500.00
  • National Institutes of Health: $261,401.00
  • National Institutes of Health: $259,068.00

ASJC

  • Medicine(all)

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