Bai Baobao, Zeng Guangwei, Chen Ruirui, Ai Yongfei, Qiang Hua
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Cardiology, Second Affiliated Hospital, Military Medical University of The Air Force, Xi'an, China.
J Biochem Mol Toxicol. 2021 Mar;35(3):e22686. doi: 10.1002/jbt.22686. Epub 2020 Dec 17.
The inhibitor of apoptosis-stimulating protein of p53 (iASPP) acts as a key modulator of cellular protection against oxidative stress. In the present work, we assessed the role of iASPP in the regulation of cardiomyocyte injury induced by hypoxia/reoxygenation (H/R). We found that H/R-exposed cardiomyocytes expressed decreased levels of iASPP. The upregulation of iASPP repressed H/R-induced injury by decreasing levels of apoptosis and reactive oxygen species production. The upregulation of iASPP increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and enhanced Nrf2 activation. The overexpression of Kelch-like ECH-associated protein 1 reversed iASPP-mediated promotion of Nrf2 activation. Nrf2 inhibition abrogated iASPP-mediated cardioprotective effects in H/R-exposed cardiomyocytes. Our work demonstrates that the upregulation of iASPP ameliorates H/R-induced apoptosis and oxidative stress in cardiomyocytes via potentiating Nrf2 signaling via modulation of Keap1.
p53凋亡刺激蛋白抑制剂（iASPP）作为细胞抗氧化应激保护的关键调节因子。在本研究中，我们评估了iASPP在缺氧/复氧（H/R）诱导的心肌细胞损伤调节中的作用。我们发现，暴露于H/R的心肌细胞中iASPP表达水平降低。iASPP的上调通过降低凋亡水平和活性氧产生来抑制H/R诱导的损伤。iASPP的上调增加了核因子（红细胞衍生2）样2（Nrf2）的核转位并增强了Nrf2的激活。Kelch样ECH相关蛋白1的过表达逆转了iASPP介导的Nrf2激活促进作用。Nrf2抑制消除了iASPP在暴露于H/R的心肌细胞中介导的心脏保护作用。我们的研究表明，iASPP的上调通过调节Keap1增强Nrf2信号通路，改善H/R诱导的心肌细胞凋亡和氧化应激。
