Aging and dietary restriction alter proteasome biogenesis and composition in the brain and liver.

Aging and dietary restriction alter proteasome biogenesis and composition in the brain and liver.
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DOI:
10.1016/j.mad.2009.10.003
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发表时间:
2009-11
影响因子:
5.3
通讯作者:
Keller JN
Keller JN
中科院分区:
医学3区
文献类型:
--
作者:
Dasuri K;Zhang L;Ebenezer P;Liu Y;Fernandez-Kim SO;Keller JN

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据报道,饮食限制(DR)等干预措施可改善某些组织中与年龄相关的蛋白酶体抑制,这表明蛋白酶体蛋白水解途径可能具有可塑性,有助于蛋白酶体功能的保护。目前尚不清楚衰老和DR对肝脏和大脑中蛋白酶体可塑性和蛋白酶体生物发生的影响,以前的研究也没有确定蛋白酶体可塑性,生物发生和衰老大脑和肝脏活性变化之间的联系。在本研究中,我们证明,大脑和肝脏表现出26 S和20 S蛋白酶体活性的年龄依赖性下降。此外,我们的研究表明,大脑和肝脏经历蛋白酶体可塑性的选择性变化,以及蛋白酶体生物合成响应于衰老和DR的增加,与大脑相比,肝脏表现出更强大的可塑性。最后,研究表明,衰老和DR改变了热休克蛋白90与大脑和肝脏中的20 S蛋白酶体复合物的相互作用。这些研究证实了衰老和DR后肝脏和大脑中蛋白酶体复合物的动态性质,并表明组织中蛋白酶体可塑性/生物发生与蛋白酶体活性之间的关系极其复杂。
Interventions such as dietary restriction (DR) have been reported to ameliorate age-related proteasome inhibition in some tissues, suggesting that there may be plasticity in the proteasome proteolytic pathway which contributes to the preservation of proteasome function. Currently it is not known what effects aging and DR have on proteasome plasticity and proteasome biogenesis in the liver and brain, nor have previous studies identified the links between changes in proteasome plasticity, biogenesis, and activity in the aging brain and liver. In the present study we demonstrate that the brain and liver exhibit age-dependent decreases in 26S and 20S proteasome activity. Additionally, our studies demonstrate that the brain and liver undergo selective changes in proteasome plasticity, and increases in proteasome biogenesis in response to aging and DR, with the liver exhibit more robust plasticity as compared to the brain. Lastly, studies demonstrated that aging and DR alter the interaction of Hsp90 with the 20S proteasome complex in the brain and liver. These studies affirm the dynamic nature of the proteasome complexes in both the liver and brain following aging and DR, and indicate that the relationship between proteasome plasticity/biogenesis and proteasome activity in tissues is extremely complex.
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