Reaction of aspirin with cysteinyl residues of lens gamma-crystallins: a mechanism for the proposed anti-cataract effect of aspirin.

Incubation of lens crystallins with aspirin inhibits the development of opacities caused by cyanate. Cyanate-induced opacities are thought to be due to carbamylation of the lysyl residues which causes a decrease in the protein charge and subsequent conformational changes that permit disulfide bonding. Because aspirin can also react with lysyl residues, it has been proposed that the aspirin inhibition of cataractogenesis is due to acetylation of the lysyl residues which would block their reaction with cyanate. However, acetylation of lysyl residues also lowers the protein charge and would be expected to effect changes in protein conformation similar to those caused by carbamylation. Therefore, acetylation of the lysyl residues is not a satisfactory explanation for the inhibitory effect of aspirin on lens opacification. Our investigations of the reactions of cyanate and aspirin with bovine gamma II-crystallins show that the cysteinyl residues are also carbamylated and acetylated at pH 7.4. At this pH, the carbamylation at the cysteinyl residues is reversible, leading to regeneration of the thiol group and disulfide bonding. In contrast, the acetylation at cysteinyl residues is stable at pH 7.4 and can prevent disulfide bonding. This difference in stability explains how cyanate promotes, and aspirin inhibits, cataractogenesis.