SIRT1 regulates dendritic development in hippocampal neurons.
SIRT1 regulates dendritic development in hippocampal neurons.
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SIRT1 调节海马神经元树突状发育。
DOI：
10.1371/journal.pone.0047073
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Inestrosa NC
中科院分区：
文献类型：
--
作者：
Codocedo JF;Allard C;Godoy JA;Varela-Nallar L;Inestrosa NC
正确的神经元连接需要树突的分枝。SIRT1是一种依赖NAD+的组蛋白脱乙酰酶，与衰老和长寿有关，在神经元中，SIRT1与神经元分化和神经保护有关。本研究探讨了SIRT1在体外培养的海马神经元树突状细胞发育中的作用。体外培养的海马神经元中，SIRT1编码SIRT1或缺乏催化活性的SIRT1H363Y。过度表达SIRT1的神经元树突分支增加，而过度表达SIRT1H363Y的神经元树突的复杂性降低。SIRT1的作用可以通过白藜芦醇来模拟，白藜芦醇是一种众所周知的SIRT1激活剂，它对过度表达SIRT1H363Y的神经元没有影响，表明白藜芦醇的作用是由SIRT1特异性介导的。此外，过度表达SIRT1的海马神经元对Aβ聚集体诱导的树突状营养不良具有抵抗力，这种作用依赖于SIRT1的脱乙酰酶活性。我们的发现表明SIRT1在海马神经元树突分支的发育和维持中起作用，并提示这些作用是由ROCK信号通路介导的。
Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway.
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影响因子：
48
作者：
Bonda, David J.;Lee, Hyoung-gon;Camins, Antoni;Pallas, Merce;Casadesus, Gemma;Smith, Mark A.;Zhu, Xiongwei
通讯作者：
Zhu, Xiongwei
影响因子：
11.4
作者：
Kim, Dohoon;Nguyen, Minh Dang;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei
影响因子：
2.9
作者：
BANKER, GA;COWAN, WM
通讯作者：
COWAN, WM
Rho-kinase in Vivo的肌球蛋白磷酸酶的肌球蛋白结合亚基（MB）的磷酸化。
DOI：
10.1083/jcb.147.5.1023
发表时间：
1999-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kawano Y;Fukata Y;Oshiro N;Amano M;Nakamura T;Ito M;Matsumura F;Inagaki M;Kaibuchi K
通讯作者：
Kaibuchi K
影响因子：
5.3
作者：
Charych, Erik I.;Akum, Barbara F.;Firestein, Bonnie L.
通讯作者：
Firestein, Bonnie L.