Changes in 20S subunit composition are largely responsible for altered proteasomal activities in experimental autoimmune encephalomyelitis.
Changes in 20S subunit composition are largely responsible for altered proteasomal activities in experimental autoimmune encephalomyelitis.
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DOI：
10.1111/j.1471-4159.2012.07699.x
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发表时间：
2012-05
影响因子：
4.7
通讯作者：
Bizzozero OA
中科院分区：
文献类型：
--
作者：
Zheng J;Dasgupta A;Bizzozero OA
我们最近报道，MOG 肽诱导的实验性自身免疫性脑脊髓炎 (EAE) 小鼠小脑中的蛋白酶体肽酶活性发生改变。为了确定这些波动是否是由蛋白酶体激活/失活和/或单个β亚基水平的变化引起的，我们通过蛋白质印迹表征了蛋白酶体亚基的组成。结果表明，急性 EAE 中蛋白酶体肽酶活性的升高与诱导型 β 亚基表达的增加相关，而慢性 EAE 中蛋白酶体肽酶活性的下降与标准 β 亚基数量的减少相关。使用纯标准 (s) 和免疫 (i) 20S 颗粒进行校准，我们确定催化亚基水平的变化解释了 EAE 中肽酶活性的所有波动。研究发现 i-20S 和 s-20S 蛋白酶体以相似的效率降解羰基化 β-肌动蛋白，这表明 EAE 中蛋白质羰基的量可能由两个核心颗粒的活性控制。我们还发现急性 EAE 中蛋白酶体激活剂 PA28 水平增加，抑制剂 PI31 水平降低，反映了对炎症的反应。另一方面，慢性 EAE 中 PA700 和 PA28 水平升高可能是由于该阶段蛋白酶体活性降低所致。这些发现对于理解炎症性脱髓鞘疾病中蛋白酶体生理学的改变至关重要。
We recently reported that the proteasomal peptidase activities are altered in the cerebellum of mice with MOG peptide-induced experimental autoimmune encephalomyelitis (EAE). To determine whether these fluctuations are caused by proteasome activation/inactivation and/or changes in the levels of individual β subunits, we characterized the proteasome subunit composition by western blotting. The results show that the rise in proteasomal peptidase activity in acute EAE correlates with an augmented expression of inducible β subunits whereas the decline in activity in chronic EAE correlates with a reduction in the amount of standard β subunits. Using pure standard (s) and immuno (i) 20S particles for calibration, we determined that the changes in the levels of catalytic subunits account for all of the fluctuations in peptidase activities in EAE. The i-20S and s-20S proteasome were found to degrade carbonylated β-actin with similar efficiency, suggesting that the amount of protein carbonyls in EAE may be controlled by the activity of both core particles. We also found an increase in proteasome activator PA28 and a decrease in inhibitor PI31 levels in acute EAE, reflecting a response to inflammation. Elevated levels of PA700 and PA28 in chronic EAE, on the other hand, may occur in response to diminished proteasomal activity in this phase. These findings are central towards understanding the altered proteasomal physiology in inflammatory demyelinating disorders.
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影响因子：
5.6
作者：
Klare, Nicola;Seeger, Michael;Dahlmann, Burkhardt
通讯作者：
Dahlmann, Burkhardt
影响因子：
4.2
作者：
Bizzozero, OA;Ziegler, JL;Bolognani, F
通讯作者：
Bolognani, F
影响因子：
4.7
作者：
Kabashi, E.;Agar, J. N.;Durham, H. D.
通讯作者：
Durham, H. D.
影响因子：
4.4
作者：
Kremer, Marcel;Henn, Anja;Groettrup, Marcus
通讯作者：
Groettrup, Marcus
影响因子：
5.4
作者：
Fissolo, Nicolas;Kraus, Marianne;Weissert, Robert
通讯作者：
Weissert, Robert