کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8326486 | 1539976 | 2007 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Lower expression of catalytic and structural subunits of the proteasome contributes to decreased proteolysis in peripheral blood T lymphocytes during aging
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کلمات کلیدی
ECLUbiquitin proteasome pathwayDNPHNELMP7LMP24-hydroxy-2-nonenal - 4-هیدروکسی-2 غیرنالNFκB - NFKBUpP - بالاenhanced chemiluminescence - بهبود شیمیایی لومنdinitrophenol - دینیتروفنلAging - سالخوردگیnuclear factor kappa B - فاکتور هسته ای کاپا BT lymphocytes - لنفوسیتهای TLipid-peroxidation - لیپید پراکسیداسیونProteasome - پروتئازومCarbonylation - کربناته شدن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Aging, in the immune system, is characterized by a decreased ability to respond to exogenous insults, resulting in increased susceptibility to infections and blunted response to vaccination. While significant age-associated deficits in immune function have been documented, the underlying molecular mechanisms are still being investigated. A consistent decline in the proteolytic activity of the proteasome has been demonstrated with advancing age, implicating an important role for the proteasome in immune senescence, by studies that largely employed proteasome-enriched preparations from cell lysates. With the availability of novel cell permeable active site probes designed specifically for assaying proteasomal activity in live cells, we now confirm our earlier data demonstrating lower catalytic activity of the proteasome in primary human T cells obtained from the elderly when compared to those from young donors. Loss in proteasomal catalytic activity translated into a loss in functional activity, as was observed in a degradation assay employing an ubiquitinated protein substrate, Ub-IκBα. Unlike fluorogenic peptide substrates, use of ubiquitinated protein substrates not only confer greater stringency in terms of proteasomal hydrolysis, but also involve the participation of the19S regulatory component. This age-associated loss in proteasomal activity is accompanied by alteration in the levels of catalytic, structural and regulatory subunits, with no change in that of the11S activator or the inhibitor PAAF1. Oxidative modification, such as carbonylation and lipid-peroxidation, of proteasomal subunits was also detected in T cells from the elderly. Thus, oxidative modification and lower levels of proteasomal subunits contribute to decreased proteolytic activity during immune-senescence.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 39, Issue 4, 2007, Pages 799-809
Journal: The International Journal of Biochemistry & Cell Biology - Volume 39, Issue 4, 2007, Pages 799-809
نویسندگان
Subramaniam Ponnappan, Huib Ovaa, Usha Ponnappan,