P53-cyclophilin D Mediates Renal Tubular Cell Apoptosis in Ischemia-reperfusion-induced Acute Kidney Injury

Overview

Journal Am J Physiol Renal Physiol

Publisher American Physiological Society

Specialties Nephrology
Physiology

Date 2019 Jul 25

PMID 31339772

Citations 15

Authors

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

Affiliations

Soon will be listed here.

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.

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