Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson’s disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl₂) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner. Then we tested the role of manganese chloride on histone acetyltransferase (HAT) and histone deacetylase (HDAC). The results showed that MnCl₂ increased the activity of HDAC but decreased that of HAT in PC12 cells. Further experiments showed that MnCl₂ selectively increased the expression levels of HDAC3 and HDAC4 rather than HDAC1 and HDAC2, but decreased that of HAT in PC12 cells and SHSY5Y cells. Pretreatment with the HAT inhibitor anacardic acid (AA) enhanced manganese-induced decrease in cell viability and apoptosis, but HDAC inhibition by TSA drug had an opposite effect in PC12 cells. Collectively, MnCl₂ inhibited the acetylation of core histones in cell culture models of PD, and that inhibition of HDAC activity by TSA protects against manganese-induced cell death, indicating that histone acetylation may represent key epigenetic changes in manganese-induced dopaminergic neurotoxicity.

锰的神经毒性表现为帕金森样症状，基底神经节中多巴胺能神经元的变性是其主要病理特征。锰神经毒性研究可能有助于更好地理解帕金森氏病的机制。在这里，我们检查了锰对组蛋白乙酰化的影响，组蛋白乙酰化是染色质的主要表观遗传变化，可以调节基因表达，染色质重塑，细胞周期进程，DNA修复和细胞凋亡。在这项研究中，我们发现氯化锰（MnCl ₂）可以以时间依赖性方式显着抑制PC12细胞和SHSY5Y细胞中组蛋白H3和H4的乙酰化。然后，我们测试了氯化锰对组蛋白乙酰转移酶（HAT）和组蛋白脱乙酰酶（HDAC）的作用。结果表明，MnCl₂在PC12细胞中增加了HDAC的活性，但降低了HAT的活性。进一步的实验表明，MnCl ₂在PC12细胞和SHSY5Y细胞中选择性地提高了HDAC3和HDAC4的表达水平，而不是HDAC1和HDAC2的表达水平，但降低了HAT的表达水平。用HAT抑制剂漆树酸（AA）预处理可增强锰诱导的细胞活力和凋亡的降低，但TSA药物对HDAC的抑制作用在PC12细胞中却有相反的作用。总体而言，MnCl ₂抑制PD细胞培养模型中核心组蛋白的乙酰化，TSA抑制HDAC活性可防止锰诱导的细胞死亡，这表明组蛋白乙酰化可能代表锰诱导的多巴胺能神经毒性的关键表观遗传学变化。