Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury

被引：102
作者：
Zhao, Chuanyan [1 ]
Chen, Zhuyun [1 ]
Xu, Xuegiang [1 ]
An, Xiaofei [2 ]
Duan, Suyan [1 ]
Huang, Zhimin [1 ]
Zhang, Chengning [1 ]
Wu, Lin [1 ]
Zhang, Bo [1 ]
Zhang, Aihua [3 ,4 ]
Xing, Changying [1 ]
Yuan, Yanggang [1 ]
机构：
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Nephrol, Nanjing, Jiangsu, Peoples R China
[2] Jiangsu Prov Hosp Chinese Med, Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Nanjing Childrens Hosp, Dept Nephrol, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Inst Pediat, Nanjing, Jiangsu, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2017年 / 350卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Pink1; Parkin; Mitophagy; Mitochondrial dysfunction; Cisplatin; AKI; MITOCHONDRIAL DYSFUNCTION; MECHANISMS; AUTOPHAGY;
D O I：
10.1016/j.yexcr.2016.12.015
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. In cultured human renal proximal tubular cells, we found that knockdown of Pink1/Parkin induced the aggravation of mitochondrial function, leading to the increase of cell injury through inhibition of mitophagy. Additionally, the overexpression of Pink1/Parkin protected against cisplatin-induced mitochondrial dysfunction and cell injury by promoting mitophagy. Our results provide clear evidence that Pink1/Parkin-dependent mitophagy has identified potential targets for the treatment of cisplatin-induced AKI.
引用
收藏
页码：390 / 397
页数：8
相关论文
共 28 条
[1]  
Akabane S., 2016, J BIOL CHEM
[2]   The pathways of mitophagy for quality control and clearance of mitochondria [J].
Ashrafi, G. ;
Schwarz, T. L. .
CELL DEATH AND DIFFERENTIATION, 2013, 20 (01) :31-42
[3]   Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity [J].
Cao, LC ;
Honeyman, TW ;
Cooney, R ;
Kennington, L ;
Scheid, CR ;
Jonassen, JA .
KIDNEY INTERNATIONAL, 2004, 66 (05) :1890-1900
[4]   Mitochondrial dysfunction in the pathophysiology of renal diseases [J].
Che, Ruochen ;
Yuan, Yanggang ;
Huang, Songming ;
Zhang, Aihua .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2014, 306 (04) :F367-F378
[5]   Mitophagy: mechanisms, pathophysiological roles, and analysis [J].
Ding, Wen-Xing ;
Yin, Xiao-Ming .
BIOLOGICAL CHEMISTRY, 2012, 393 (07) :547-564
[6]   Mitochondrial dysfunction in inherited renal disease and acute kidney injury [J].
Emma, Francesco ;
Montini, Giovanni ;
Parikh, Samir M. ;
Salviati, Leonardo .
NATURE REVIEWS NEPHROLOGY, 2016, 12 (05) :267-280
[7]   Multiphoton Imaging Reveals Differences in Mitochondrial Function between Nephron Segments [J].
Hall, Andrew M. ;
Unwin, Robert J. ;
Parker, Nadeene ;
Duchen, Michael R. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (06) :1293-1302
[8]   Autophagy in proximal tubules protects against acute kidney injury [J].
Jiang, Man ;
Wei, Qingqing ;
Dong, Guie ;
Komatsu, Masaaki ;
Su, Yunchao ;
Dong, Zheng .
KIDNEY INTERNATIONAL, 2012, 82 (12) :1271-1283
[9]   Mitochondria and Mitophagy The Yin and Yang of Cell Death Control [J].
Kubli, Dieter A. ;
Gustafsson, Asa B. .
CIRCULATION RESEARCH, 2012, 111 (09) :1208-1221
[10]   Raising awareness of acute kidney injury: a global perspective of a silent killer [J].
Lewington, Andrew J. P. ;
Cerda, Jorge ;
Mehta, Ravindra L. .
KIDNEY INTERNATIONAL, 2013, 84 (03) :457-467
123