Premium
Proteasome activity declines in aged macrophages
Author(s) -
Cui Xuelin,
Shang Fu,
Wu Dayong,
Meydani Simin Nikbin
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a983-b
Subject(s) - proteasome , ubiquitin , proteolysis , chemistry , endocrinology , medicine , enzyme , trypsin , biology , biochemistry , gene
The ubiquitin‐proteasome pathway is involved in regulation of a variety of biologically important processes including antigen presentation by macrophages (Mφ). Age‐related decrease in proteasome activity has been reported in other tissues. However, the effect of aging on the ubiquitin‐proteasome pathway in Mφ has not been systematically studied. Thioglycollate‐elicited Mφ from young (4–6 mo) and Old (24–26 mo) male C57BL/6NIA mice were collected by lavage. Mφ from old mice exhibited significantly lower activity of all three proteasome peptidases [chymotrypsin‐like activity (young vs old, Mean ± SE): 100 ± 13 vs 62 ± 4, p<0.05; trypsin‐like activity: 100 ± 4 vs 56 ± 3, p<0.01; acidic activity: 100 ± 7 vs 58 ± 6, p<0.01]. The age‐related decrease in proteasome activity was not due to decreased expression of proteasome subunits, since levels of C2 and S1 subunits were higher in old Mφ than young (C2: 100 ± 20 vs 167 ± 13, p<0.05; S1: 100 ± 15 vs 183 ± 20, p<0.01) while there was no significant age‐related difference in levels of α5, LMP2 and LMP7. The decrease in proteasome activity was associated with an increase in the levels of ubiquitin conjugates. Furthermore, the levels of 2 ubiquitination‐related enzymes, E1 and E2 (Ubc7), were significantly higher in old Mφ than young. The age‐related decline in proteasome activity and the paralleled increase in levels of ubiquitin conjugates indicate that the function of the ubiquitin‐proteasome pathway is impaired in the aged Mφ. The decrease in proteasome activity in Mφ might contribute to the age‐related decline in the ability of Mφ to present antigens to T cells, a proteasome dependent process. Supported by USDA #58‐1950‐9‐001 and NIA #R01 AG009140 ‐10A1.