Plk2是响应氧化应激而诱导的细胞应激响应因子。然而,Plk2在急性肾损伤(AKI)中的作用尚未明确.我们以前发现Plk2是Nrf2响应细胞应激的相互作用因子,因为Plk2在Nrf2依赖的网络中被上调。这里,我们显示,p53,Plk2,p21cip1和染色质结合的Nrf2的水平在小鼠肾组织或用顺铂或甲氨蝶呤处理的NRK52E细胞中均上调.p53上调Plk2导致顺铂处理的NRK52E细胞中可溶性和染色质部分中Nrf2的增加。始终如一,Plk2的耗尽抑制了Nrf2的水平。值得注意的是,Plk2在Ser40处直接磷酸化Nrf2,这促进了其与p21cip1的相互作用并易位到细胞核中,以激活对AKI的抗氧化和抗炎因子。一起,这些研究结果表明,Plk2可能通过磷酸化和激活Nrf2作为抗氧化和抗炎调节因子,从而保护肾细胞免受肾脏毒性物质的侵害,因此Plk2和Nrf2协同作用,保护肾细胞免受有害应激的侵害并使其存活.
The
Plk2 is a cellular stress-responsive factor that is induced in response to oxidative stress. However, the roles of
Plk2 in acute kidney injury (AKI) have not been clarified. We previously found that
Plk2 is an interacting factor of Nrf2 in response to cellular stress, since
Plk2 is upregulated in the Nrf2-dependent network. Here, we show that the levels of p53, Plk2, p21cip1, and chromatin-bound Nrf2 were all upregulated in kidney tissues of mice or NRK52E cells treated with either cisplatin or methotrexate. Upregulation of Plk2 by p53 led to an increase of Nrf2 in both soluble and chromatin fractions in cisplatin-treated NRK52E cells. Consistently, depletion of
Plk2 suppressed the levels of Nrf2. Of note, Plk2 directly phosphorylated Nrf2 at Ser40, which facilitated its interaction with p21cip1 and translocation into the nuclei for the activation of anti-oxidative and anti-inflammatory factors in response to AKI. Together, these findings suggest that Plk2 may serve as an anti-oxidative and anti-inflammatory regulator through the phosphorylation and activation of Nrf2 to protect kidney cells from kidney toxicants and that Plk2 and Nrf2 therefore work cooperatively for the protection and survival of kidney cells from harmful stresses.