Abstract
Various post-translational lens crystallins modifications result in structural and functional insults, contributing to the development of lens opacity and cataract disorders. Lens crystallins are potential targets of homocysteinylation, particularly under hyperhomocysteinemia which has been indicated in various eye diseases. Since both homocysteinylation and acetylation primarily occur on protein free amino groups, we applied different spectroscopic methods and gel mobility shift analysis to examine the possible preventive role of acetylation against homocysteinylation. Lens crystallins were extensively acetylated in the presence of acetic anhydride and then subjected to homocysteinylation in the presence of homocysteine thiolactone (HCTL). Extensive acetylation of the lens crystallins results in partial structural alteration and enhancement of their stability, as well as improvement of α-crystallin chaperone-like activity. In addition, acetylation partially prevents HCTL-induced structural alteration and aggregation of lens crystallins. Also, acetylation protects against HCTL-induced loss of α-crystallin chaperone activity. Additionally, subsequent acetylation and homocysteinylation cause significant proteolytic degradation of crystallins. Therefore, further experimentation is required in order to judge effectively the preventative role of acetylation on the structural and functional insults induced by homocysteinylation of lens crystallins.
Highlights
The cytoplasm of fiber cells in the vertebrate eye lenses is enriched with long-lived and wellordered proteins known as crystallins [1]
Acetylation of lysine residues with acetic anhydride (Ac2O), prevents formation of advanced glycation end products (AGEs), improves chaperone-like activity and the anti-apoptotic properties of α-Cry [21]. Since both acetylation and homocysteinylation largely occur on lysine residues, the purpose of the current study was to take advantage of acetylation as a possible protective approach against structural and functional insults induced by homocysteinylation in lens crystallins
While the acetylated proteins are resistant to aggregation; the non-acetylated protein counterparts demonstrate a propensity for aggregation
Summary
The cytoplasm of fiber cells in the vertebrate eye lenses is enriched with long-lived and wellordered proteins known as crystallins [1]. Acetylation Protects Lens Crystallins against Homocysteinylation homology [4] These two protein subunits form oligomeric assemblies of various size ranges which are important in the terms of their ability to allow proper refraction of light in eye lenses. The chaperone function of this protein is highly important to maintain the transparency of the eye lens over decades Due to their limited turnover during lifespan, lens crystallins can accumulate numerous post-translational modifications lead to alterations in their structure and interactions which eventually disturb the proper refractive index of the lenticular tissues [1, 7, 8]. Various modifications of these proteins interrupt their fine interactions and induce conformational change and aggregation of these proteins which eventually culminate in lens opacification and cataract [1, 7]
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