MECHANISM OF SELENIUM INDUCED CATARACT

Project: Research project

Description

The overall goal of this project has been to provide a biochemical
mechanism for formation of selenite cataract in young rats. Our previous
work has shown that partial proteolysis of Beta-crystallins by calcium-
activated protease, calpain II, plays a central role in the mechanism of
selenite cataract. The current proposal is focused on providing a
biochemical mechanism on how partially truncated B-crystallin
polypeptides become insoluble in selenite cataract and other models of
cataract using older rat lenses. Aim #1 will use an in vitro model of crystallin insolubilization to
determine why removal of the N-termini on B-crystallin subunits by
calpain causes insolubilization. Aim #2 will directly compare results of the in vitro studies of
proteolytic insolubilization to insolubilization occurring in the in vivo
model of selenite cataract and in other models of cataract using older
rat lenses. Aim #3 will determine the role of a-crystallin chaperon activity in
proteolytic insolubilization of B-crystallins. Techniques to be used include: two dimensional electrophoresis followed
by N-terminal protein sequencing of spots, fast atom mass spectroscopy,
laser light scattering, UV circular dichroism, protein-protein cross-
linking, and turbidity measurements. The results will extend our on-
going studies concerning how crystallins become insoluble in cataracts
and how crystallins interact in normal lens. This knowledge may be used
in the future to develop drugs for prevention of cataract by maintaining
the solubility of lens proteins.
StatusFinished
Effective start/end date9/30/8112/31/04

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $273,771.00
  • National Institutes of Health: $263,979.00
  • National Institutes of Health
  • National Institutes of Health: $281,919.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Selenium
Cataract
Selenious Acid
Crystallins
Lenses
Epithelium
beta-Crystallins
Proteolysis
Calcium
Calpain
Peptides
Rodentia
Electrophoresis
Diamide
Light

ASJC

  • Medicine(all)