METHODS: Human peripheral blood mononuclear cells (PBMC) were treated with the Nrf2 activator tBHQ in combination with zinc to examine a possible correlation between zinc and redox homeostasis. Therefore, mRNA expression of Nrf2 and its downstream molecules NQO1 and HO-1 were investigated, as well as the protein synthesis of these. In addition, the effect of zinc on histone deacetylase 3 (HDAC3), which is a negative regulator for Nrf2 activity, was analyzed.
RESULTS: Either mRNA, protein expression or both of Nrf2, NQO1 and HO-1 are influenced by zinc. The analysis of HDAC3 shows a negative correlation between its activity and increasing zinc concentrations. By inhibiting HDAC3 zinc stabilizes Nrf2.
CONCLUSIONS: The results indicate that zinc emphasizes the induction of Nrf2 by its activator tBHQ through increasing gene and protein expression. Additionally, zinc supplementation inhibits HDAC3 activity resulting in reduced Keap1 mRNA expression and thereby stabilizing cytoplasmatic Nrf2. These findings suggests that zinc supplementation has beneficial effects on the redox balance in human cells.
方法:用Nrf2激活剂tBHQ联合锌处理人外周血单核细胞(PBMC),以检查锌与氧化还原稳态之间可能的相关性。因此,研究了Nrf2及其下游分子NQO1和HO-1的mRNA表达,以及这些蛋白质的合成。此外,锌对组蛋白去乙酰化酶3(HDAC3)的影响,它是Nrf2活性的负调节剂,被分析。
结果:无论是mRNA,Nrf2,NQO1和HO-1的蛋白质表达或两者都受锌的影响。HDAC3的分析显示其活性与增加的锌浓度之间呈负相关。通过抑制HDAC3锌稳定Nrf2。
结论:结果表明,锌通过增加基因和蛋白质表达来强调其激活剂tBHQ对Nrf2的诱导。此外,锌补充抑制HDAC3活性,导致Keap1mRNA表达降低,从而稳定细胞质Nrf2。这些发现表明锌补充对人细胞中的氧化还原平衡具有有益作用。