Breakdown of oxidized proteins as a part of secondary antioxidant defenses in mammalian cells.

The degradation of oxidized proteins is an essential part of antioxidant defenses against free radical attack. Selective degradation of oxidatively damaged proteins allows proteolytic systems to function directly in the removal of useless cellular debris and therefore prevent the accumulation of potentially toxic fragments or large aggregates of cross-linked proteins. The degradation of oxidized proteins in dividing mammalian cells after hydrogen peroxide treatment has been demonstrated. Cells are able to increase proteolysis rates after treatment with moderate levels of oxidants. The role of proteasome in the removal of oxidized proteins has been demonstrated by treatment of cells with an anti-sense oligodesoxynucleotide to the proteasome C2 subunit gene. This treatment decreases the proteasome content of the cells and prevents increased proteolysis rates after hydrogen peroxide treatment. Thus proteasome clearly plays a role in the removal of oxidized proteins. As part of antioxidant defenses the proteasome provides a second line of defense against the numerous radicals and oxidants which contact cells during their lifetime. The degradation of oxidatively damaged proteins enables-cells to recover from a moderate oxidant attack.