Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Biochim Biophys Acta Mol Basis Dis. 2019 Aug 1;1865(8):2068-2081. doi: 10.1016/j.bbadis.2018.10.024. Epub 2018 Oct 29.
Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.
由于汞(Hg)在环境中广泛分布,其暴露仍然是一个主要的公共卫生关注点。有机汞化合物,如甲基汞(MeHg),已被广泛研究,特别是因为它们的先天效应。在这方面,研究 MeHg 诱导的神经毒性的分子机制对于理解其毒性作用和开发预防措施至关重要。蛋白质的翻译后修饰(PTMs),如磷酸化、泛素化和乙酰化,对于蛋白质的正常功能至关重要,并在细胞内稳态的调节中发挥重要作用。许多 PTMs 的快速和瞬时性质允许有效地进行应激响应信号转导。本综述总结了 MeHg 诱导的神经毒性中 PTMs 的最新知识,包括最常见的 PTMs,以及氧化应激诱导的 PTMs 和抗氧化蛋白的 PTMs。虽然 PTMs 代表维持细胞内稳态的重要分子机制,并参与 MeHg 的神经毒性作用,但我们远未完全了解它们的作用,需要进一步研究以增加我们对 MeHg 诱导的神经毒性中 PTMs 的了解。