Non-tryptophan fluorescence and high molecular weight protein formation in lens crystallins of rats with chronic galactosemia: prevention by the aldose reductase inhibitor sorbinil.

Abstract:

:Crystallin-bound non-tryptophan fluorescence and protein cross-linking were studied in chronic galactosemia. Fluorescence (excitation/emission--370/440 nm) was significantly higher in galactosemic rats compared to controls (P less than 0.001). Accumulation of fluorescence was significantly reduced both in water soluble (P less than 0.001) and insoluble (P less than 0.005) lens fractions in galactosemic rats receiving the aldose reductase inhibitor sorbinil. High performance liquid chromatography of water soluble lens crystallins showed an increase in the content of high molecular weight proteins and the fluorescence associated with it. Sorbinil partly prevented the formation of such fluorescent high molecular weight proteins. Under reducing conditions, sodium dodecyl sulfate polyacrylamide gel electrophoresis of water soluble proteins revealed a distinct high molecular weight protein of 60 kDa in galactosemia. Sorbinil treatment completely abolished the formation of this protein. Western blotting using rabbit antiserum to bovine alpha-, beta- and gamma-crystallins revealed the presence of gamma, but not alpha- and beta-crystallins in the 60-kDa protein. Formation of this protein may result from trimerization of gamma-crystallins or from an association of gamma-crystallin with a non-crystallin cytosolic protein or mixed protein cross-linking of gamma-crystallins with membrane protein(s). The present study shows that polyol pathway in cataractogenesis also extends to protein cross-linking and formation of fluorescent compounds, the nature of which remains to be elucidated.

journal_name

Exp Eye Res

authors

Nagaraj RH,Monnier VM

doi

10.1016/0014-4835(90)90153-l

subject

Has Abstract

pub_date

1990-10-01 00:00:00

pages

411-8

issue

4

eissn

0014-4835

issn

1096-0007

pii

0014-4835(90)90153-L

journal_volume

51

pub_type

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