p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury

Huan Yang, Ruizhao Li, Li Zhang, Shu Zhang, Wei Dong, Yuanhan Chen, Weidong Wang, Chunling Li, Zhiming Ye, Xingchen Zhao, Zhilian Li, Yanhua Wu, Mengxi Zhang, Shuangxin Liu, Zheng Dong, Xinling Liang

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F1311-F1317
JournalAmerican journal of physiology. Renal physiology
Volume317
Issue number5
DOIs
StatePublished - Nov 1 2019

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Keywords

  • cyclophilin D
  • ischemic renal injury
  • membrane permeability transition pore
  • p53

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Yang, H., Li, R., Zhang, L., Zhang, S., Dong, W., Chen, Y., Wang, W., Li, C., Ye, Z., Zhao, X., Li, Z., Wu, Y., Zhang, M., Liu, S., Dong, Z., & Liang, X. (2019). p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury. American journal of physiology. Renal physiology, 317(5), F1311-F1317. https://doi.org/10.1152/ajprenal.00072.2019