Alpha-crystallin acting as a molecular chaperone protects catalase against steroid-induced inactivation.
A link between corticosteroid therapy and the development of cataract has been known for many years. However, the precise underlying molecular mechanism of pathology has not been characterised, although a role for direct deleterious interactions between corticosteroids and lenticular proteins has been investigated. Alpha-crystallin is a major lens protein that has exhibited chaperone properties in vitro. Catalase is a ubiquitous enzyme that is an important scavenger of hydrogen peroxide in vivo. The corticosteroid prednisolone-21-hemisuccinate was found to inactivate bovine liver catalase, in vitro in a progressive manner. Coincubation of alpha-crystallin with catalase in a 1:2 molar ratio (one alpha-crystallin to two catalase molecules) fully protected against this inactivation. The protection was specific. Aspirin-like analgesics, putative anti-cataract drugs offered no such protection.
Hook
D W
DW
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.
Harding
J J
JJ
D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors*; D002417:Cattle; D003459:Crystallins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D018832:Molecular Chaperones / Q000494:pharmacology*; D009994:Osmolar Concentration; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology
D003459:Crystallins; D004791:Enzyme Inhibitors; D018832:Molecular Chaperones; D011239:Prednisolone; D002374:Catalase; C021322:prednisolone hemisuccinate