α-突触核蛋白过表达抑制 14-3-3θ 的转录。
α-Synuclein overexpression represses 14-3-3θ transcription.
机构信息
Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Civitan International Research Center 560D, 1719 6th Avenue South, Birmingham, AL, 35294, USA.
出版信息
J Mol Neurosci. 2013 Nov;51(3):1000-9. doi: 10.1007/s12031-013-0086-5. Epub 2013 Aug 4.
Abstract
Previous gene microarray studies have shown that expression of 14-3-3θ is significantly decreased in an α-synuclein transgenic mouse model. In this study, we tested whether α-synuclein can regulate 14-3-3θ transcription. We demonstrate that the 14-3-3θ mRNA level is decreased in SH-SY5Y cells overexpressing α-synuclein. Luciferase activity under the control of the 14-3-3θ promoter is reduced both in stable SH-SY5Y cells constitutively overexpressing α-synuclein and in doxycycline-inducible SH-SY5Y cells upon α-synuclein induction, suggesting that the regulation of 14-3-3θ by α-synuclein occurs at the transcriptional level. Knockdown of α-synuclein by RNA interference does not increase the 14-3-3θ mRNA level. These findings suggest that α-synuclein represses 14-3-3θ transcription under pathologic conditions, but that regulation of 14-3-3θ expression is not a function of endogenous α-synuclein at baseline.
摘要
先前的基因微阵列研究表明，在α-突触核蛋白转基因小鼠模型中，14-3-3θ 的表达显著降低。在这项研究中，我们测试了α-突触核蛋白是否可以调节 14-3-3θ 的转录。我们证明，在过度表达α-突触核蛋白的 SH-SY5Y 细胞中，14-3-3θ mRNA 水平降低。在稳定表达α-突触核蛋白的 SH-SY5Y 细胞和在诱导α-突触核蛋白后可诱导的 SH-SY5Y 细胞中，受 14-3-3θ 启动子控制的荧光素酶活性降低，表明α-突触核蛋白对 14-3-3θ 的调节发生在转录水平。RNA 干扰下调α-突触核蛋白不会增加 14-3-3θ mRNA 水平。这些发现表明，在病理条件下，α-突触核蛋白抑制 14-3-3θ 的转录，但在基线时，14-3-3θ 的表达调节不是内源性α-突触核蛋白的功能。
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