Curcumin protects against manganese-induced neurotoxicity in rat by regulating oxidative stress-related gene expression via H3K27 acetylation.
Curcumin protects against manganese-induced neurotoxicity in rat by regulating oxidative stress-related gene expression via H3K27 acetylation.
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DOI：
10.1016/j.ecoenv.2022.113469
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发表时间：
2022-03
影响因子：
6.8
通讯作者：
Yue Yang;Ying Liu;Anliu Zhang;Shunfang Tang;Q. Ming;Chunyan Ao;Yan Liu;Changzhe Li;Chun Yu;Hua Zhao;Li Chen;Jun Li
中科院分区：
文献类型：
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作者：
Yue Yang;Ying Liu;Anliu Zhang;Shunfang Tang;Q. Ming;Chunyan Ao;Yan Liu;Changzhe Li;Chun Yu;Hua Zhao;Li Chen;Jun Li
长期接触锰会导致神经退行性疾病，称为锰中毒，但其机制仍不清楚，也没有具体的治疗方法。氧化应激被广泛认为是锰引起的神经毒性的主要原因之一。近年来，组蛋白乙酰化在神经退行性疾病中的作用受到广泛关注。姜黄素是从姜黄根茎中提取的天然多酚化合物，具有抗氧化和神经保护特性。因此，我们的目的是基于组蛋白乙酰化修饰的可逆性，从组蛋白乙酰化的角度研究姜黄素是否以及如何预防锰诱导的神经毒性。在这项研究中，大鼠接受或不接受姜黄素治疗，并长期接触锰。结果表明，锰处理降低了氧化应激相关基因启动子区H3K18乙酰化和H3K27乙酰化蛋白的表达，并抑制了这些基因的表达。然而，姜黄素增加了锰超氧化物歧化酶（SOD2）基因启动子处的H3K27乙酰化水平，促进了SOD2基因的表达。姜黄素治疗后，大鼠纹状体的氧化损伤以及学习和记忆功能障碍得到改善。综上所述，我们的结果表明，组蛋白乙酰化对氧化应激的调节可能是锰诱导神经毒性的关键机制。此外，姜黄素改善锰诱导的神经毒性可能是由于SOD2基因启动子处H3K27乙酰化激活增加介导的氧化损伤的减轻。
Long-term manganese exposure causes a neurodegenerative disorder referred to as manganese poisoning, but the mechanism remains unclear and no specific treatment is available. Oxidative stress is widely recognised as one of the main causes of manganese-induced neurotoxicity. In recent years, the role of histone acetylation in neurodegenerative diseases has been widely concerned. curcumin is a natural polyphenol compound extracted from the rhizome of turmeric and exhibits both antioxidant and neuroprotective properties. Therefore, we aimed to investigate whether and how curcumin protects against manganese-induced neurotoxicity from the perspective of histone acetylation, based on the reversibility of histone acetylation modification. In this study, rats were treated with or without curcumin and subjected to long-term manganese exposure. Results that treatment of manganese decreased the protein expression of H3K18 acetylation and H3K27 acetylation at the promoters of oxidative stress-related genes and inhibited the expression of these genes. Nevertheless, curcumin increased the H3K27 acetylation level at the manganese superoxide dismutase (SOD2) gene promoter and promoted the expression of SOD2 gene. Oxidative damage in the rat striatum as well as learning and memory dysfunction were ameliorated after curcumin treatment. Taken together, our results suggest that the regulation of oxidative stress by histone acetylation may be a key mechanism of manganese-induced neurotoxicity. In addition, curcumin ameliorates Mn-induced neurotoxicity may be due to alleviation of oxidative damage mediated by increased activation of H3K27 acetylation at the SOD2 gene promoter.