Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 42, Issue 4, Pages 541-551Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2006.11.020
Keywords
aging; proteasome; oxidative stress; GSH; ROS; T lymphocytes; immune dysregulation; immune senescence
Funding
- NCRR NIH HHS [M01 RR 1288] Funding Source: Medline
- NIA NIH HHS [R01 AG013081, R01 AG 13081] Funding Source: Medline
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Proteasome is a major cellular organelle responsible for the regulated turnover of both normal and misfolded proteins. Recent reports from our laboratory have implicated lowered proteasomal chymotryptic activity to be responsible for decreased induction of the transcription factor NF kappa B in T lymphocytes during aging. In this study, we have further analyzed the basis for this decline in proteasomal function, by focusing on the role of oxidative stress. On exposure to the prooxidant BSO, both ATP-stimulatable 26S and ATP-independent 20S proteasomal catalytic activity could be down-regulated in T cells from young donors, mimicking the decline observed in T cells from the elderly. Loss in these catalytic activities, following exposure to prooxidant stimulus, also resulted in a decline in both activation-induced proliferation and degradation of the inhibitor I kappa B alpha, with concomitant increase in the accumulation of carbonylated proteins, mimicking responses seen in T cells from the elderly. Pretreatment with an antioxidant, NAC, could override prooxidant-mediated, but not age-associated, decrease in both 20S and 26S proteasomal activities. These results suggest that the decrease in proteasomal activities observed during aging may be secondary to oxidative stress and underlie immune senescence. (c) 2006 Elsevier Inc. All rights reserved.
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