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Manganese Chloride Induces Histone Acetylation Changes in Neuronal Cells: Its Role in Manganese-Induced Damage

Manganese Chloride Induces Histone Acetylation Changes in Neuronal Cells: Its Role in Manganese-Induced Damage

Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu

Neurotoxicology. 2018 Mar;65:255-263.

PMID: 29155171

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP13446349-A	Manganese chloride		13446-34-9	Price

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