2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004090768v1 16/7/1985    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, H. Articles by Baliga, R. Search for Related Content PubMed PubMed Citation Articles by Liu, H. Articles by Baliga, R.

Endoplasmic Reticulum Stress–Associated Caspase 12 Mediates Cisplatin-Induced LLC-PK1 Cell Apoptosis

Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi

Address correspondence to: Dr. Radhakrishna Baliga, Department of Pediatrics, Division of Nephrology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. Phone: 601-984-5970; Fax: 601-815-5902; E-mail: rbaliga{at}ped.umsmed.edu

Received for publication September 14, 2004. Accepted for publication April 7, 2005.

Reactive oxygen metabolites are important mediators in cisplatin-induced apoptosis in renal tubular epithelial cells (LLC-PK1). Mitochondria have been implicated to play a principal role in cisplatin-induced apoptosis. Caspase 12, an endoplasmic reticulum (ER)-specific caspase, participates in apoptosis under ER stress. Cytochrome P450 system is crucial to the generation of reactive oxygen metabolites and is present at high concentration in the ER. The direct role of caspase 12 in any model of renal injury has not previously been described. In this study, cleavage of procaspase 12 preceded that of caspases 3 and 9 after cisplatin treatment of LLC-PK1 cells. The active form of caspase 8 was not detected throughout the course of study. Preincubation of the LLC-PK1 cells with the caspase 9 inhibitor did not attenuate caspase 3 activation and provided no significant protection. Caspase 3 inhibitor provided only modest protection against cisplatin-induced apoptosis. LLC-PK1 cells that were transfected with anti–caspase 12 antibody significantly attenuated cisplatin-induced apoptosis. Taken together, these data indicate that caspase 12 plays a pivotal role in cisplatin-induced apoptosis. It is proposed that the oxidative stress that results from the interaction of cisplatin with the ER cytochrome P450 leads to activation of procaspase 12, resulting in apoptosis.

This article has been cited by other articles:

				C. A. Rabik, M. L. Fishel, J. L. Holleran, K. Kasza, M. R. Kelley, M. J. Egorin, and M. E. Dolan Enhancement of Cisplatin [cis-Diammine Dichloroplatinum (II)] Cytotoxicity by O6-Benzylguanine Involves Endoplasmic Reticulum Stress J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 442 - 452. [Abstract] [Full Text] [PDF]

				M. Kitamura Endoplasmic reticulum stress and unfolded protein response in renal pathophysiology: Janus faces Am J Physiol Renal Physiol, August 1, 2008; 295(2): F323 - F334. [Abstract] [Full Text] [PDF]

				F. Yu, J. Megyesi, and P. M. Price Cytoplasmic initiation of cisplatin cytotoxicity Am J Physiol Renal Physiol, July 1, 2008; 295(1): F44 - F52. [Abstract] [Full Text] [PDF]

				C. Yang, V. Kaushal, S. V. Shah, and G. P. Kaushal Autophagy is associated with apoptosis in cisplatin injury to renal tubular epithelial cells Am J Physiol Renal Physiol, April 1, 2008; 294(4): F777 - F787. [Abstract] [Full Text] [PDF]

				M. Peyrou, P. E. Hanna, and A. E. Cribb Cisplatin, Gentamicin, and p-Aminophenol Induce Markers of Endoplasmic Reticulum Stress in the Rat Kidneys Toxicol. Sci., September 1, 2007; 99(1): 346 - 353. [Abstract] [Full Text] [PDF]

				F. Yu, J. Megyesi, R. L. Safirstein, and P. M. Price Involvement of the CDK2-E2F1 pathway in cisplatin cytotoxicity in vitro and in vivo Am J Physiol Renal Physiol, July 1, 2007; 293(1): F52 - F59. [Abstract] [Full Text] [PDF]

				K. Johansson, K. Ahlen, R. Rinaldi, K. Sahlander, A. Siritantikorn, and R. Morgenstern Microsomal glutathione transferase 1 in anticancer drug resistance Carcinogenesis, February 1, 2007; 28(2): 465 - 470. [Abstract] [Full Text] [PDF]

				B. S. Kasinath, M. M. Mariappan, K. Sataranatarajan, M. J. Lee, and D. Feliers mRNA Translation: Unexplored Territory in Renal Science J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3281 - 3292. [Abstract] [Full Text] [PDF]

				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]

				S. Muruganandan and A. E. Cribb Calpain-Induced Endoplasmic Reticulum Stress and Cell Death following Cytotoxic Damage to Renal Cells Toxicol. Sci., November 1, 2006; 94(1): 118 - 128. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673