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Steroid adduct formation with lens crystallins
Andrew I Jobling1, Robert C Augusteyn
1National Vision Research Institute of Australia, 386 Cardigan Street, Carlton, Victoria, 3053, Australia.
Clinical & Experimental Optometry
|December 17, 2002
Summary
Glucocorticoids can form adducts with lens proteins, especially alpha-crystallin. However, this study suggests steroid-protein adducts are unlikely to cause steroid-induced cataracts.
Area of Science:
- Ophthalmology
- Biochemistry
- Molecular Biology
Background:
- Prolonged glucocorticoid use can lead to steroid-induced cataracts.
- Steroid-protein adduct formation is hypothesized to be a key mechanism in cataractogenesis.
Purpose of the Study:
- To investigate the reaction between bovine lens proteins and glucocorticoids.
- To determine the structural impact of steroid-protein adduct formation.
Main Methods:
- Bovine lens proteins incubated with dexamethasone or prednisolone at varying concentrations and temperatures.
- Analysis of protein structure, size, solubility, conformation, and oxidation using gel permeation chromatography, SDS-PAGE, and spectroscopy.
Main Results:
- Covalent glucocorticoid-protein adducts formed with alpha-, beta-, and gamma-crystallins, with alpha-crystallin showing highest reactivity.
- No significant changes in crystallin size, solubility, or conformation were observed.
- A slight decrease in protein sulphydryl content was noted, but no intermolecular disulphide bonds formed.
Conclusions:
- Steroids do bind to lens proteins, particularly alpha-crystallin.
- The formation of these steroid-protein adducts does not appear to be the primary cause of steroid-induced cataracts.