LMP2 Knock-Out Mice Have Reduced Proteasome Activities and Increased Levels of Oxidatively Damaged Proteins

Abstract

The proteasome is a large intracellular protease, composed of multiple subunits, that is present in all eukaryotic cells. Proteasome inhibition is known to occur during normal aging, and is believed to contribute towards an age-related increase in oxidative stress, although at present the mechanisms responsible for mediating age-related changes in proteasome activity have not been elucidated. At present the relationship between proteasome subunit expression, proteasome activity, and protein oxidation during normal aging has not been elucidated. In the present study we observed that the absence of LMP2, a specific proteasome subunit, decreases proteasome activities in both the brain and liver, with increased levels of protein oxidation occurring in both tissues. Results from this study demonstrate for the first time that individual proteasome subunits are important for the regulation of age-related changes in both proteasome activity and protein oxidation.