MICROPEROXIDASES CATALYTICALLY DEGRADE REACTIVE OXYGEN SPECIES AND MAY BE ANTICATARACT AGENTS

mu Px-11, a ferriheme undecapeptide proteolytic degradation product of cytochrome C is shown to be a peroxidase with broad specificity degra ding H2O2 and tertiary butyl hydroperoxide. It is also capable of effe ctively eliminating superoxide and hydroxyl radical. The peroxidase lo ses activity in the presence of peroxide unless it is stabilized by as corbate (Asc) or solutions such as aqueous humor or medium 199. While thiol but not disulfides inactivates the mu Px-11, it is not inhibited in the presence of the rat lens which has a high GSH content. mu Px-1 1 at concentrations 10 to 50 fold greater than are required to achieve good protective activity exhibits no toxicity based on cell viability , ATP levels and lens transparency after long-term incubations of alph a TN4-1 cells or cultured rat lens. The peroxidase is capable of prote cting cultured rat lenses from photochemical stress where H2O2, O-2(.- ) and OH. are generated based on transparency, choline transport, epit helial cell viability and protein integrity as indicated by SDS-PAGE o f the rat lens protein. In the absence of the peroxidase, extensive ep ithelial cell death and other degradative changes are observed. The DN A of alpha TN4-1 cells can also be protected from H2O2 induced single strand breaks by the mu Px-11. The overall results suggest that a numb er of cytochrome C proteolytic degradation products are peroxidases wh ich may be effective anti-cataract agents protecting the lens from oxi dative stress. (C) 1997 Academic Press Limited.