Effects of modifications of alpha-crystallin on its chaperone and other properties.
The role of alpha-crystallin, a small heat-shock protein and chaperone, may explain how the lens stays transparent for so long. alpha-Crystallin prevents the aggregation of other lens crystallins and proteins that have become unfolded by 'trapping' the protein in a high-molecular-mass complex. However, during aging, the chaperone function of alpha-crystallin becomes compromised, allowing the formation of light-scattering aggregates that can proceed to form cataracts. Within the central part of the lens there is no turnover of damaged protein, and therefore post-translational modifications of alpha-crystallin accumulate that can reduce chaperone function; this is compounded in cataract lenses. Extensive in vitro glycation, carbamylation and oxidation all decrease chaperone ability. In the present study, we report the effect of the modifiers malondialdehyde, acetaldehyde and methylglyoxal, all of which are pertinent to cataract. Also modification by aspirin, which is known to delay cataract and other diseases, has been investigated. Recently, two point mutations of arginine residues were shown to cause congenital cataract. 1,2-Cyclohexanedione modifies arginine residues, and the extent of modification needed for a change in chaperone function was investigated. Only methylglyoxal and extensive modification by 1,2-cyclohexanedione caused a decrease in chaperone function. This highlights the robust nature of alpha-crystallin.
Derham
Barry K
BK
Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW, U.K.
Harding
John J
JJ
D000818:Animals; D003459:Crystallins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism; D008315:Malondialdehyde / Q000494:pharmacology; D018832:Molecular Chaperones / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology; D011817:Rabbits; D013050:Spectrometry, Fluorescence
D003459:Crystallins; D018832:Molecular Chaperones; D008315:Malondialdehyde; D011765:Pyruvaldehyde