p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury.
p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury.
复制标题
p53-cyclophilin D 在缺血再灌注诱导的急性肾损伤中介导肾小管细胞凋亡。
DOI：
10.1152/ajprenal.00072.2019
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Liang Xinling
中科院分区：
文献类型：
--
作者：
Yang Huan;Li Ruizhao;Zhang Li;Zhang Shu;Dong Wei;Chen Yuanhan;Wang Weidong;Li Chunling;Ye Zhiming;Zhao Xingchen;Li Zhilian;Wu Yanhua;Zhang Mengxi;Liu Shuangxin;Dong Zheng;Liang Xinling
缺血再灌注（I/R）诱导的急性肾损伤（I/R-AKI）有利于线粒体通透性转换孔（mPTP）开放和随后的细胞死亡。亲环素D（CypD）是mPTP的重要组成部分，最近的研究结果表明p53-CypD复合物参与细胞死亡。为了评估p53-CypD在I/R-AKI后的作用，我们检验了p53-CypD复合物通过mPTP开放介导I/R-AKI中肾小管细胞凋亡的假设。与正常对照组和假手术对照组相比，I/R-AKI大鼠中p53和裂解的caspase-3的表达显著增加。使用ATP耗竭的体外模型确定潜在的机制。使用CypD抑制剂环孢菌素A或siRNA抑制ATP耗尽的HK-2细胞中的p53的mPTP开放防止线粒体膜去极化并减少凋亡。此外，在ATP耗尽的HK-2细胞中，p53与CypD结合。这些结果表明，p53-CypD复合物通过mPTP开放介导I/R-AKI中的肾小管细胞凋亡。
Ischemia-reperfusion (I/R)-induced acute kidney injury (I/R-AKI) favors mitochondrial permeability transition pore (mPTP) opening and subsequent cell death. Cyclophilin D (CypD) is an essential component of the mPTP, and recent findings have implicated the p53-CypD complex in cell death. To evaluate the role of p53-CypD after I/R-AKI, we tested the hypothesis that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening. Expression of p53 and cleaved caspase-3 was significantly increased in rats subjected to I/R-AKI compared with normal controls and sham-operated controls. The underlying mechanisms were determined using an in vitro model of ATP depletion. Inhibition of mPTP opening using the CypD inhibitor cyclosporin A or siRNA for p53 in ATP-depleted HK-2 cells prevented mitochondrial membrane depolarization and reduced apoptosis. Furthermore, p53 bound to CypD in ATP-depleted HK-2 cells. These results suggest that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening.