Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis

The American Journal of Physiology
W LieberthalJ Levine

Abstract

We have examined the mechanisms of cell death induced by cisplatin in primary cultures of mouse proximal tubular cells. High concentrations of cisplatin (800 microM) led to necrotic cell death over a few hours. Much lower concentrations of cisplatin (8 microM) led to apoptosis, which caused loss of the cell monolayer over several days. Necrosis was characterized by a cytosolic swelling and early loss of plasma membrane integrity. In contrast, early features of cells undergoing apoptosis included cell shrinkage and loss of attachment to the monolayers. Nuclear chromatin became condensed and fragmented in apoptosing cells. These features were absent in necrotic cells. DNA electrophoresis of cells exposed to 800 microM cisplatin yielded a "smear" pattern, due to random DNA degradation. In contrast, the DNA of apoptosing cells demonstrated a "ladder" pattern resulting from internucleosomal DNA cleavage. Antioxidants delayed cisplatin-induced apoptosis but not necrosis. Thus the mechanism of cell death induced by cisplatin is concentration dependent. Reactive oxygen species play a role in mediating apoptosis but not necrosis induced by cisplatin.

Citations

May 1, 2002·Current Opinion in Nephrology and Hypertension·Ramon Bonegio, Wilfred Lieberthal
May 15, 2003·American Journal of Physiology. Renal Physiology·Grazyna NowakRick G Schnellmann
Jul 17, 2003·American Journal of Physiology. Renal Physiology·Ganesan Ramesh, W Brian Reeves
Nov 6, 2003·American Journal of Physiology. Renal Physiology·Takaharu IchimuraJoseph V Bonventre
Sep 30, 2004·American Journal of Physiology. Renal Physiology·Lucia CilentiAntonis S Zervos
Apr 4, 2008·American Journal of Physiology. Renal Physiology·Abdulla K SalahudeenHe Zhe
Jul 26, 2019·International Journal of Molecular Sciences·Giovanna PrianteFranca Anglani
May 16, 2001·American Journal of Physiology. Renal Physiology·E ErkanP Devarajan
Jan 15, 2004·American Journal of Physiology. Renal Physiology·Reiko SunamiHirofumi Makino
Nov 6, 2009·American Journal of Physiology. Renal Physiology·Guie DongZheng Dong
Mar 17, 2011·Human & Experimental Toxicology·Kanittha PongjitPithi Chanvorachote
May 12, 2000·American Journal of Physiology. Renal Physiology·F ShiraishiA Agarwal
Feb 29, 2000·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·N Ueda, S V Shah
Feb 5, 2002·Annual Review of Physiology·Steven C Borkan, Steven R Gullans
Apr 10, 2003·American Journal of Physiology. Renal Physiology·Kazuhiko TsuruyaMitsuo Iida
Sep 13, 2001·American Journal of Physiology. Renal Physiology·W LieberthalJ S Levine
Aug 3, 2007·American Journal of Physiology. Renal Physiology·Qingqing WeiZheng Dong
Aug 19, 2005·American Journal of Physiology. Cell Physiology·Wei QianMasayasu Inoue
Jan 25, 2012·Journal of Toxicologic Pathology·Takeki UeharaToshiyuki Maruyama
Jan 16, 2009·American Journal of Physiology. Renal Physiology·Navjotsingh PablaZheng Dong
Feb 17, 2006·Journal of the American Society of Nephrology : JASN·Manchang LiuHamid Rabb
May 20, 2011·American Journal of Physiology. Renal Physiology·Duk Hoon KimWon Kim
Feb 1, 2013·American Journal of Physiology. Renal Physiology·Shi-kun YangYashpal S Kanwar
Dec 15, 2015·American Journal of Physiology. Renal Physiology·Tess Victoria DupreLeah J Siskind
Mar 15, 2018·International Journal of Molecular Sciences·Haesol LeeYou-Kyoung Choi
Jan 24, 2019·American Journal of Physiology. Renal Physiology·Mari WatanabeNobuyuki Takahashi
Mar 28, 2008·American Journal of Physiology. Cell Physiology·Elbert L LeeYasunobu Okada
Jul 27, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Heloísa Della Coletta FrancescatoTerezila Machado Coimbra
Nov 10, 2011·Toxins·Ronald P MillerWilliam Brian Reeves
Jan 17, 2019·International Journal of Molecular Sciences·Xu CaoJinsong Bian
Aug 19, 2004·American Journal of Physiology. Renal Physiology·Man JiangZheng Dong
Mar 20, 2020·International Journal of Molecular Sciences·Anja UrbschatMichaela Jung
Mar 19, 2021·Frontiers in Medicine·Yasuaki Hirooka, Yuji Nozaki
Mar 30, 2021·Journal of Experimental Pharmacology·Paul B TchounwouSanjay Kumar
Mar 20, 2013·Experimental and Molecular Pathology·Rungwasee RattanavichPravin C Singhal
Feb 23, 2021·American Journal of Physiology. Renal Physiology·Fei DengYashpal S Kanwar
Mar 26, 2002·Journal of the American Society of Nephrology : JASN·Moon Soo ParkPrasad Devarajan

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