Department of Anatomy, Brain Korea 21, Korea University College of Medicine, Seoul, Korea.
Brain Res. 2010 Feb 8;1313:1-8. doi: 10.1016/j.brainres.2009.11.078. Epub 2009 Dec 5.
Hes6 is a member of hairy/enhancer of split (Hes) family that plays a role in the cell proliferation and differentiation. Recently, we found that Hes6 is involved in the regulation of cell proliferation via p53-dependent pathway. In addition to the proliferating regions, brain regions where early post-mitotic neurons are enriched also exhibited Hes6 and p53 mRNA expression. Because p53 is involved in the post-mitotic neuronal apoptosis, here we investigated whether Hes6 can influence the neuronal survival/death. Overexpression of wild-type Hes6 and its mutants induced the apoptosis of primary cultured cortical neurons. In addition, neuronal apoptosis by Hes6 overexpression was markedly blunted in p53(-/-) or Bax(-/-) cortical neurons, suggesting that these pro-apoptotic effects are mediated by p53- and Bax-dependent pathway. However, transactivation-defective mutants of Hes6 also enhanced neuronal apoptosis, suggesting that apoptogenic activity of Hes6 is not directly related to its role in the transcriptional regulation. We propose that Hes6 may play a significant role in the neuronal cell death and/or pathological neurodegeneration via activation of p53 signaling.
Hes6 是 hairy/enhancer of split（Hes）家族的成员，在细胞增殖和分化中发挥作用。最近，我们发现 Hes6 通过 p53 依赖性途径参与细胞增殖的调节。除了增殖区域外，富含早期有丝后神经元的脑区也表现出 Hes6 和 p53 mRNA 的表达。由于 p53 参与有丝后神经元凋亡，因此我们研究了 Hes6 是否会影响神经元的存活/死亡。野生型 Hes6 及其突变体的过表达诱导原代皮质神经元凋亡。此外，在 p53(-/-)或 Bax(-/-)皮质神经元中，Hes6 过表达引起的神经元凋亡明显减弱，表明这些促凋亡作用是通过 p53 和 Bax 依赖性途径介导的。然而，Hes6 的转录激活缺陷突变体也增强了神经元凋亡，表明 Hes6 的促凋亡活性与其在转录调控中的作用没有直接关系。我们提出 Hes6 可能通过激活 p53 信号通路在神经元细胞死亡和/或病理性神经退行性变中发挥重要作用。
