The degradation of abnormal and post-translationally modified proteins, e.g., oxidatively damaged proteins, mediated by the proteasome, the major alkaline protease activity of the cell. It has been suggested that a decline in alkaline protease activity leads to the age-related cellular accumulation of oxidatively damaged proteins. We have found that proteasomal peptidase activities exhibit age-related alterations that are similar to the changes observed in response to interferon-γ (IFN-γ) (J. Gerontol. 51A: B316-B322, 1996). IFN-γ action is known to alter proteasome subunit composition (subunits δ and X are replaced by LMP2 and LMP7, respectively). Consistent with the IFN-γ analogy, LMP2 and LMP7 mRNA levels (Northern analysis) increase ∼1(X)% and ∼50%, respectively, between 6 and 24 months of age. FR suppresses these increases. Subunit protein levels (Western analysis) are increased proportionately with age and FR suppresses these increases. Subunit mRNA alterations are seen in liver and kidney but not in spleen or skeletal muscle. In conclusion, liver and kidney proteasome structure and function is altered with age and FR modulates these alterations. The physiological ramifications of these changes are currently unknown and are under investigation.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology