Oxidative modifications to crystallins induced in calf lenses in vitro by hydrogen peroxide.

Calf lenses which are incubated in solutions of 1-150 mM H2O2 for 24 hr remain clear at 20 degrees C. While insoluble lens protein increases by at most 2-3%, we find extensive oxidation of exposed protein thiols, major shifts in the size distribution of crystallins, and progressive generation of more acidic polypeptides. Some of these oxidative modifications are reversible with reducing agent. beta H-Crystallins are particularly susceptible to oxidation: disulfide-bonded soluble aggregates form at low H2O2 levels, while irreversible dissociation to beta L-crystallins occurs at high H2O2 concentration. The gamma-crystallins are particularly prone to charge modification. In contrast, the size and charge distributions of alpha-crystallins appear to be virtually unaffected by H2O2.