Proteasome inhibition modulates kinase activation in neural cells: relevance to ubiquitination, ribosomes, and survival.
Proteasome inhibition modulates kinase activation in neural cells: relevance to ubiquitination, ribosomes, and survival.
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DOI：
10.1002/jnr.22147
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发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Keller, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Zhang, Le;Ebenezer, Philip J.;Dasuri, Kalavathi;Bruce-Keller, Annadora J.;Liu, Ying;Keller, Jeffrey N.
在这项研究中，我们检查了 N2a 神经细胞中已建立的信号转导级联、p44/42 丝裂原激活蛋白激酶 (ERK1/2) 和 Jun N 末端激酶 (JNK) 通路是否因蛋白酶体抑制而发生改变。此外，我们试图阐明这些信号转导途径对蛋白酶体抑制的多种下游效应的相对贡献。我们的数据表明 ERK1/2 和 JNK 因蛋白酶体抑制而被激活。蛋白酶体抑制剂 (MG132) 的清除会增强 ERK1/2 的激活并改善 JNK 的激活。使用已确定的 MAPK 抑制剂进行治疗会导致蛋白酶体抑制剂毒性增加，而与 JNK 抑制剂一起孵育可显着减弱蛋白酶体抑制剂的毒性。随后的研究表明，抑制 ERK1/2 和 JNK 活性不会改变施用蛋白酶体抑制剂后泛素化蛋白的总体增加。类似地，在神经细胞中施用蛋白酶体抑制剂后，ERK1/2 和 JNK 活性似乎在多核糖体的破坏中没有发挥作用。总之，这些数据表明 ERK1/2 和 JNK 激活可能在调节蛋白酶体抑制引起的神经化学紊乱和神经毒性中发挥不同的作用。
In this study we examined whether established signal transduction cascades, p44/42 mitogen activated protein kinase (ERK1/2) and Jun N-terminal kinases (JNK) pathways, are altered in N2a neural cells in response to proteasome inhibition. Additionally, we sought to elucidate the relative contribution of these signal transduction pathways to the multiple downstream effects of proteasome inhibition. Our data indicate that ERK1/2 and JNK are activated in response to proteasome inhibition. Washout of proteasome inhibitor (MG132) results in an enhancement of ERK1/2 activation and amelioration of JNK activation. Treatment with an established MAPK inhibitor resulted in an increase in proteasome inhibitor toxicity, while incubation with JNK inhibitor was observed to significantly attenuate proteasome inhibitor toxicity. Subsequent studies demonstrate that inhibition of ERK1/2 and JNK activity does not alter the gross increase in ubiquitinated protein following proteasome inhibitor administration. Similarly, ERK1/2 and JNK activity do not appear to play a role in the disruption of polysomes following proteasome inhibitor administration in neural cells. Together, these data indicate that ERK1/2 and JNK activation may play differential roles in modulating neurochemical disturbances and neurotoxicity induced by proteasome inhibition.
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影响因子：
4.7
作者：
Keller, JN;Hanni, KB;Markesbery, WR
通讯作者：
Markesbery, WR
影响因子：
4.8
作者：
Jiang, HY;Wek, RC
通讯作者：
Wek, RC
影响因子：
4.8
作者：
Chondrogianni, N;Stratford, FLL;Gonos, ES
通讯作者：
Gonos, ES
DOI：
10.1523/jneurosci.2139-08.2008
发表时间：
2008-10-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fioravante D;Liu RY;Byrne JH
通讯作者：
Byrne JH
影响因子：
4.8
作者：
Chondrogianni, N;Tzavelas, C;Gonos, ES
通讯作者：
Gonos, ES