p21 protects cardiomyocytes against ischemia-reperfusion injury by inhibiting oxidative stress
p21 protects cardiomyocytes against ischemia-reperfusion injury by inhibiting oxidative stress
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DOI：
10.3892/mmr.2018.8382
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发表时间：
2018-03-01
影响因子：
3.4
通讯作者：
Yang, Jie-Fu
中科院分区：
文献类型：
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作者：
Li, Hong;Zou, Tong;Yang, Jie-Fu
缺血性心脏病是一个主要的健康威胁，每年在世界范围内造成大量死亡。氧化应激是缺血再灌注（IR）损伤中细胞死亡的主要原因之一。细胞周期蛋白依赖性激酶抑制剂1A（称为p21）在保护组织免受IR损伤方面很重要，但其机制尚不清楚。本研究以H9c2心源性心肌细胞为模型，体外研究心肌IR损伤。分别用逆转录-定量聚合酶链反应和western blotting检测mRNA和蛋白的表达水平。用荧光染料2,7-二氯二氢荧光素测定了活性氧的水平。目前的数据表明，在暴露于OGD/R的H9c2细胞中，p21的表达被肿瘤蛋白p53 （p53）上调。p21保护H9c2细胞免受OGD/ r诱导的氧化应激。此外，p21介导nf - e2相关因子-2 （Nrf2）的上调，Nrf2是抗氧化反应的调节因子，从而抑制OGD/R下H9c2细胞的细胞死亡。因此，激活p53/p21/Nrf2信号通路可能是限制IR期间氧化损伤的重要适应性反应。
Ischemic heart disease is a major health threat, resulting in a large number of mortalities annually worldwide. Oxidative stress is one of the main causes of cell death during ischemia-reperfusion (IR) injury. Cyclin dependent kinase inhibitor 1A (known as p21) is important in protecting tissues against IR injury, however the mechanism remains unknown. In the present study, oxygen-glucose deprivation and subsequent reoxygenation (OGD/R) in H9c2 heart-derived myocytes was used as a model to study myocardial IR injury in vitro. mRNA and protein expression levels were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The levels of reactive oxygen species were measured using the fluorescence dye 2,7-dichlorodihydrofluorescein diacetate. The present data demonstrated that p21 expression was upregulated by tumor protein p53 (p53) in H9c2 cells exposed to OGD/R. p21 protected H9c2 cells against OGD/R-induced oxidative stress. In addition, p21 mediated upregulation of NF-E2-related factor-2 (Nrf2), a regulator of antioxidant responses, which in turn suppressed cell death in H9c2 cells subjected to OGD/R. Thus, activation of the p53/p21/Nrf2 signaling pathway may be an important adaptive response that limits oxidative injury during IR.