AJP - Renal AJP: Regulatory, Integrative and Comparative Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 287: F1140-F1147, 2004. First published August 17, 2004; doi:10.1152/ajprenal.00262.2004
0363-6127/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/6/F1140    most recent
00262.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (32)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jiang, M.
Right arrow Articles by Dong, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, M.
Right arrow Articles by Dong, Z.

Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity

Man Jiang,1 Xiaolan Yi,1 Stephen Hsu,2 Cong-Yi Wang,3 and Zheng Dong1,4

1Department of Cellular Biology and Anatomy, 2Department of Oral Biology and Maxillofacial Pathology, and 3Center for Genomic Medicine, Medical College of Georgia, Augusta 30912; and 4Medical Research Service, Department of Veterans Affairs Medical Center, Augusta, Georgia 30904

Submitted 15 July 2004 ; accepted in final form 17 August 2004

Tubular damage by cisplatin leads to acute renal failure, which limits its use in cancer therapy. In tubular cells, a primary target for cisplatin is presumably the genomic DNA. However, the pathway relaying the signals of DNA damage to tubular cell death is unclear. In response to DNA damage, the tumor suppressor gene p53 is induced and is implicated in subsequent DNA repair and cell death by apoptosis. The current study was designed to examine the role of p53 in cisplatin-induced apoptosis in cultured rat kidney proximal tubular cells. Cisplatin at 20 µM induced apoptosis in ~70% of cells, which was partially suppressed by carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone (VAD), a general caspase inhibitor. Of interest, cisplatin-induced apoptosis was also suppressed by pifithrin-{alpha}, a pharmacological inhibitor of p53. Cisplatin-induced caspase activation was completely inhibited by VAD, but only partially by pifithrin-{alpha}. Early during cisplatin treatment, p53 was phosphorylated and upregulated. The p53 activation was blocked by pifithrin-{alpha}, but not by VAD. Bcl-2 expression abolished cisplatin-induced apoptosis without blocking p53 phosphorylation or induction. The results suggest that p53 activation might be an early signal for apoptosis during cisplatin treatment. To further determine the role of p53, tubular cells were stably transfected with a dominant-negative mutant of p53 with diminished transcriptional activity. Expression of the mutant attenuated cisplatin-induced apoptosis and caspase activation. In conclusion, the results support an important role for p53 in cisplatin-induced apoptosis in renal tubular cells. p53 May regulate apoptosis through the transcription of apoptotic genes.

caspase; renal tubule


Address for reprint requests and other correspondence: Z. Dong, Dept. of Cellular Biology and Anatomy, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912 (E-mail: zdong{at}mail.mcg.edu)




This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
X. Han, J. Yue, and R. W. Chesney
Functional TauT Protects Against Acute Kidney Injury
J. Am. Soc. Nephrol., June 1, 2009; 20(6): 1323 - 1332.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Jiang, C.-Y. Wang, S. Huang, T. Yang, and Z. Dong
Cisplatin-induced apoptosis in p53-deficient renal cells via the intrinsic mitochondrial pathway
Am J Physiol Renal Physiol, May 1, 2009; 296(5): F983 - F993.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. Singaravelu, K. Devalaraja-Narashimha, B. Lastovica, and B. J. Padanilam
PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia
Am J Physiol Renal Physiol, April 1, 2009; 296(4): F847 - F858.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
N. Pabla, R. F. Murphy, K. Liu, and Z. Dong
The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity
Am J Physiol Renal Physiol, March 1, 2009; 296(3): F505 - F511.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
T. A. Sutton, J. Wilkinson, H. E. Mang, N. L. Knipe, Z. Plotkin, M. Hosein, K. Zak, J. Wittenborn, and P. C. Dagher
p53 regulates renal expression of HIF-1{alpha} and pVHL under physiological conditions and after ischemia-reperfusion injury
Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1666 - F1677.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Jiang and Z. Dong
Regulation and Pathological Role of p53 in Cisplatin Nephrotoxicity
J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 300 - 307.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Dong, L. Wang, C.-Y. Wang, T. Yang, M. V. Kumar, and Z. Dong
Induction of Apoptosis in Renal Tubular Cells by Histone Deacetylase Inhibitors, a Family of Anticancer Agents
J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 978 - 984.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. Bhatt, L. Feng, N. Pabla, K. Liu, S. Smith, and Z. Dong
Effects of targeted Bcl-2 expression in mitochondria or endoplasmic reticulum on renal tubular cell apoptosis
Am J Physiol Renal Physiol, March 1, 2008; 294(3): F499 - F507.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
Q. Wei, G. Dong, T. Yang, J. Megyesi, P. M. Price, and Z. Dong
Activation and involvement of p53 in cisplatin-induced nephrotoxicity
Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1282 - F1291.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Zhou, M. Zhang, and S. S. Atherton
Tumor Necrosis Factor-{alpha}-Induced Apoptosis in Murine Cytomegalovirus Retinitis
Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1691 - 1700.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
C. Brooks, J. Wang, T. Yang, and Z. Dong
Characterization of cell clones isolated from hypoxia-selected renal proximal tubular cells
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F243 - F252.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Wang, N. Pabla, C.-Y. Wang, W. Wang, P. V. Schoenlein, and Z. Dong
Caspase-mediated cleavage of ATM during cisplatin-induced tubular cell apoptosis: inactivation of its kinase activity toward p53
Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1300 - F1307.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Wang, M. P. Biju, M.-H. Wang, V. H. Haase, and Z. Dong
Cytoprotective Effects of Hypoxia against Cisplatin-Induced Tubular Cell Apoptosis: Involvement of Mitochondrial Inhibition and p53 Suppression
J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1875 - 1885.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. C. Chua, X. Liu, J. Gao, R. C. Hamdy, and B. H. L. Chua
Multiple actions of pifithrin-{alpha} on doxorubicin-induced apoptosis in rat myoblastic H9c2 cells
Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2606 - H2613.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.