Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Brain Res. 2010 Oct 1;1354:172-8. doi: 10.1016/j.brainres.2010.07.041. Epub 2010 Jul 21.
Although the pathophysiological processes involved in dopamine (DA) neuron degeneration in Parkinson's disease (PD) are not completely known, apoptotic cell death has been suggested to be involved and can be modeled in DAergic cell lines using the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP(+)). Recently, it has been suggested that histone deacetylase inhibitors (HDACIs) may reduce apoptotic cell death in various model systems. However, their utility in interfering with DA cell death remains unclear. The HDACIs sodium butyrate (NaB), valproate (VPA) and suberoylanilide hydroxamic acid (SAHA) were tested for their ability to prevent MPP(+)-mediated cytotoxicity in human derived SK-N-SH and rat derived MES 23.5 cells. All three HDACIs at least partially prevented MPP(+)-mediated apoptotic cell death. The protective effects of these HDACIs coincided with significant increases in histone acetylation. These results suggest that HDACIs may be potentially neuroprotective against DA cell death and should be explored further in animal models of PD.
虽然帕金森病（PD）中涉及多巴胺（DA）神经元变性的病理生理过程尚不完全清楚，但已经提出细胞凋亡性死亡与之相关，并可以使用线粒体毒素 1-甲基-4-苯基吡啶鎓（MPP(+))在 DA 能细胞系中进行建模。最近，有人提出组蛋白去乙酰化酶抑制剂（HDACIs）可能会减少各种模型系统中的细胞凋亡性死亡。然而，它们在干扰 DA 细胞死亡方面的效用尚不清楚。测试了组蛋白去乙酰化酶抑制剂（HDACIs）——丁酸钠（NaB）、丙戊酸钠（VPA）和琥珀酰亚胺基羟肟酸（SAHA），以评估它们预防人源 SK-N-SH 和大鼠源性 MES 23.5 细胞中 MPP(+)介导的细胞毒性的能力。这三种 HDACIs 至少部分地预防了 MPP(+)介导的细胞凋亡性死亡。这些 HDACIs 的保护作用与组蛋白乙酰化水平的显著增加相吻合。这些结果表明，HDACIs 可能对 DA 细胞死亡具有潜在的神经保护作用，应在 PD 的动物模型中进一步探索。
