Inhibition of beta-crystallin cross-linking in the Ca2+-treated lens

beta-Crystallin dimers of approximately 55,000 weight are among the early products of protein cross-linking in Ca2+-treated rabbit lens, caused by the activation of intrinsic transglutaminase; formation of the cross-linked species can be blocked by 75 mM histamine (Lorand et al, Biochemistry, 24:1525-1531, 1985). As an extension of this work, we initiated a search for more specific inhibitors of cross-linking in this system. Of the compounds tested so far, hydroxylamine, methoxyamine, bisaminoxypropane and aminoacetonitrile were particularly effective, inhibiting the generation of the cross-linked dimer in the 5 to 10 mM concentration range during a 4 hr treatment of the lens with Ca2+-ions.