Activation of proteasome by insulin-like growth factor-I may enhance clearance of oxidized proteins in the brain.
Activation of proteasome by insulin-like growth factor-I may enhance clearance of oxidized proteins in the brain.
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DOI：
10.1016/j.mad.2009.10.005
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发表时间：
2009-11
影响因子：
5.3
通讯作者：
Torres C
中科院分区：
文献类型：
--
作者：
Crowe E;Sell C;Thomas JD;Johannes GJ;Torres C
胰岛素样生长因子1（IGF-I）在神经生理学中起着重要作用。IGF-I水平在衰老过程中降低，这种降低可能对大脑中与年龄相关的变化很重要。我们研究了IGF-I对脑组织和细胞培养物中总蛋白氧化的影响。我们的研究结果表明，在额叶皮质的氧化蛋白的水平显着降低，在转基因小鼠设计过度产生IGF-I与野生型动物相比。IGF-I过度产生小鼠的额叶皮质表现出20 S和26 S蛋白酶体的高糜蛋白酶样活性。蛋白酶体也可以在细胞培养物中响应IGF-I而被激活。动力学研究表明，峰值激活的蛋白酶体在15分钟内IGF-I刺激。在缺乏IGF-I受体的R细胞中未观察到IGF-I对蛋白酶体的影响。使用特异性激酶抑制剂的实验表明，IGF-I对蛋白酶体的激活涉及磷脂酰肌醇3-激酶和哺乳动物雷帕霉素信号传导的靶点。IGF-I还减弱了蛋白酶体抑制引起的蛋白质羰基含量的增加。因此，适当水平的IGF-I可能是重要的氧化蛋白在大脑中的蛋白酶体的激活介导的过程中的消除。
The insulin-like growth factor type 1 (IGF-I) plays an important role in neuronal physiology. Reduced IGF-I levels are observed during aging and this decrease may be important to age-related changes in the brain. We studied the effects of IGF-I on total protein oxidation in brain tissues and in cell cultures. Our results indicate that in frontal cortex the level of oxidized proteins is significantly reduced in transgenic mice designed to overproduce IGF-I compared with wild-type animals. The frontal cortex of IGF-I-overproducing mice exhibited high chymotrypsin-like activity of the 20S and 26S proteasomes. The proteasome can also be activated in response to IGF-I in cell cultures. Kinetic studies revealed peak activation of the proteasome within 15 min following IGF-I stimulation. The effects of IGF-I on proteasome were not observed in R- cells lacking the IGF-I receptor. Experiments using specific kinase inhibitors suggested that activation of proteasome by IGF-I involves phosphatidyl inositol 3-kinase and mammalian target of rapamycin signaling. IGF-I also attenuated the increase in protein carbonyl content induced by proteasome inhibition. Thus, appropriate levels of IGF-I may be important for the elimination of oxidized proteins in the brain in a process mediated by activation of the proteasome.
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影响因子：
--
作者：
Davies JE;Sarkar S;Rubinsztein DC
通讯作者：
Rubinsztein DC
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
3.9
作者：
Husom, AD;Peters, EA;Ferrington, DA
通讯作者：
Ferrington, DA
影响因子：
56.9
作者：
Herbig, U;Ferreira, M;Sedivy, JM
通讯作者：
Sedivy, JM
影响因子：
4.1
作者：
Bose, S;Stratford, FLL;Rivett, AJ
通讯作者：
Rivett, AJ