National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
FEBS Lett. 2010 Jun 3;584(11):2291-7. doi: 10.1016/j.febslet.2010.03.040. Epub 2010 Mar 28.
Following our previous finding that sodium selenite induces apoptosis in human leukemia NB4 cells, we now show that the expression of the critical antioxidant enzyme manganese superoxide dismutase (MnSOD) is remarkably elevated during this process. We further reveal that reactive oxygen species (ROS), especially superoxide radicals, play a crucial role in selenite-induced MnSOD upregulation, with extracellular regulated kinase (ERK) and p53 closely implicated. Specifically, ERK2 translocates into the nucleus driven by ROS, where it directly phosphorylates p53, leading to dissociation of p53 from its inhibitory protein mouse double minute 2 (MDM2). Active p53 directly mediates the expression of MnSOD, serving as the link between ERK2 translocation and MnSOD upregulation.
继我们之前发现亚硒酸钠能诱导人白血病 NB4 细胞凋亡之后，我们现在表明在这个过程中关键的抗氧化酶锰超氧化物歧化酶 (MnSOD) 的表达显著升高。我们进一步揭示活性氧 (ROS)，特别是超氧自由基，在亚硒酸钠诱导的 MnSOD 上调中起着至关重要的作用，细胞外调节激酶 (ERK) 和 p53 密切相关。具体来说，ROS 驱动 ERK2 转位到细胞核，在那里它直接磷酸化 p53，导致 p53 与其抑制蛋白鼠双微体 2 (MDM2) 解离。活性 p53 直接介导 MnSOD 的表达，作为 ERK2 易位和 MnSOD 上调之间的联系。
