HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 44, 46263-46270, October 29, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/44/46263    most recent M406555200v1 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 Lim, S.-Y. Articles by Surh, Y.-J. Search for Related Content PubMed PubMed Citation Articles by Lim, S.-Y. Articles by Surh, Y.-J. Social Bookmarking                      What's this?

15-Deoxy-^12,14-Prostaglandin J₂ Protects against Nitrosative PC12 Cell Death through Up-regulation of Intracellular Glutathione Synthesis^*

So-Young Lim, Jung-Hee Jang, Hye-Kyung Na, Shelly C. Lu¶, Irfan Rahman||, and Young-Joon Surh**

From the College of Pharmacy, Seoul National University, Seoul 151-742, Korea, the ^¶Division of Gastrointestinal and Liver Disease, USC Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, and the ^||Department of Environmental Medicine, Division of Lung Biology and Disease, University of Rochester Medical Center, Rochester, New York 14642

Nitrosative stress with subsequent inflammatory cell death has been associated with many neurodegenerative disorders. Expression of inducible nitric-oxide synthase and production of nitric oxide (NO) have been frequently elevated in many inflammatory disorders. NO can rapidly react with superoxide anion, producing more reactive peroxynitrite. In the present study, exposure of rat pheochromocytoma (PC12) cells to the peroxynitrite donor 3-morpholinosydnonimine hydrochloride (SIN-1) induced apoptosis, which accompanied depletion of intracellular glutathione (GSH), c-Jun N-terminal kinase activation, mitochondrial membrane depolarization, the cleavage of poly(ADP-ribose)polymerase, and DNA fragmentation. During SIN-1-induced apoptotic cell death, expression of inducible cyclooxygenase (COX-2), and peroxisome proliferator-activated receptor- (PPAR) was elevated. SIN-1 treatment resulted in elevated production of 15-deoxy-^12,14-prostaglandin J₂ (15d-PGJ₂), an endogenous PPAR activator. Preincubation with 15d-PGJ₂ rendered PC12 cells resistant to nitrosative stress induced by SIN-1. 15d-PGJ₂ fortified an intracellular GSH pool through up-regulation of glutamylcysteine ligase, thereby preventing cells from SIN-1-induced GSH depletion. The above findings suggest that 15d-PGJ₂ may act as a survival mediator capable of augmenting cellular thiol antioxidant capacity through up-regulation of the intracellular GSH synthesis in response to the nitrosative insult.

Received for publication, June 11, 2004 , and in revised form, August 11, 2004.

^* This work was supported by Grant R02-2004-000-10197-0 from the Basic Research Program of the Korea Science and Engineering Foundation (to Y.-J. S.), the National Institutes of Health Grant DK-45334 (to S. C. L.), and the Environmental Health Sciences Center support ES01247 (to I. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^** To whom correspondence should be addressed: College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea. Tel.: 82-2-880-7845; Fax: 82-2-874-9775; E-mail: surh{at}plaza.snu.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E.-H. Kim, H.-K. Na, D.-H. Kim, S.-A. Park, H.-N. Kim, N.-Y. Song, and Y.-J. Surh 15-Deoxy-{Delta}12,14-prostaglandin J2 induces COX-2 expression through Akt-driven AP-1 activation in human breast cancer cells: a potential role of ROS Carcinogenesis, April 1, 2008; 29(4): 688 - 695. [Abstract] [Full Text] [PDF]

				M.-H. Li, J.-H. Jang, H.-K. Na, Y.-N. Cha, and Y.-J. Surh Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling J. Biol. Chem., September 28, 2007; 282(39): 28577 - 28586. [Abstract] [Full Text] [PDF]

				S. Qin, A. P. McLaughlin, and G. W. De Vries Protection of RPE Cells from Oxidative Injury by 15-Deoxy-{Delta}12,14-Prostaglandin J2 by Augmenting GSH and Activating MAPK Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5098 - 5105. [Abstract] [Full Text] [PDF]

				P. Bergamo, D. Luongo, F. Maurano, G. Mazzarella, R. Stefanile, and M. Rossi Conjugated linoleic acid enhances glutathione synthesis and attenuates pathological signs in MRL/MpJ-Faslpr mice J. Lipid Res., November 1, 2006; 47(11): 2382 - 2391. [Abstract] [Full Text] [PDF]

				Z.-H. Chen, Y. Yoshida, Y. Saito, A. Sekine, N. Noguchi, and E. Niki Induction of Adaptive Response and Enhancement of PC12 Cell Tolerance by 7-Hydroxycholesterol and 15-Deoxy-{Delta}12,14-Prostaglandin J2 through Up-regulation of Cellular Glutathione via Different Mechanisms J. Biol. Chem., May 19, 2006; 281(20): 14440 - 14445. [Abstract] [Full Text] [PDF]

				W. Zhou and C. R. Freed DJ-1 Up-regulates Glutathione Synthesis during Oxidative Stress and Inhibits A53T {alpha}-Synuclein Toxicity J. Biol. Chem., December 30, 2005; 280(52): 43150 - 43158. [Abstract] [Full Text] [PDF]

				Z.-H. Chen, Y. Saito, Y. Yoshida, A. Sekine, N. Noguchi, and E. Niki 4-Hydroxynonenal Induces Adaptive Response and Enhances PC12 Cell Tolerance Primarily through Induction of Thioredoxin Reductase 1 via Activation of Nrf2 J. Biol. Chem., December 23, 2005; 280(51): 41921 - 41927. [Abstract] [Full Text] [PDF]

				A Jawerbaum, R Higa, V White, E Capobianco, C Pustovrh, D Sinner, N Martinez, and E Gonzalez Peroxynitrites and impaired modulation of nitric oxide concentrations in embryos from diabetic rats during early organogenesis Reproduction, November 1, 2005; 130(5): 695 - 703. [Abstract] [Full Text] [PDF]

				K. M. Fuenzalida, M. C. Aguilera, D. G. Piderit, P. C. Ramos, D. Contador, V. Quinones, A. Rigotti, F. C. Bronfman, and M. Bronfman Peroxisome Proliferator-activated Receptor {gamma} Is a Novel Target of the Nerve Growth Factor Signaling Pathway in PC12 Cells J. Biol. Chem., March 11, 2005; 280(10): 9604 - 9609. [Abstract] [Full Text] [PDF]