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

J. Biol. Chem., Vol. 279, Issue 53, 55385-55392, December 31, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/53/55385    most recent M405858200v1 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 Eminel, S. Articles by Waetzig, V. Search for Related Content PubMed PubMed Citation Articles by Eminel, S. Articles by Waetzig, V. Social Bookmarking                      What's this?

JNK2 Translocates to the Mitochondria and Mediates Cytochrome c Release in PC12 Cells in Response to 6-Hydroxydopamine^*

Sevgi Eminel, Alexa Klettner, Lutz Roemer, Thomas Herdegen, and Vicki Waetzig

From the Institute of Pharmacology, Schleswig-Holstein University Medical Center, Campus Kiel, Hospitalstrasse 4, 24105 Kiel, Germany

6-Hydroxydopamine (6-OHDA) causes death of dopaminergic neurons by mitochondrial dysfunction with JNKs as central mediators. Here we provide novel insights into specific actions of JNK isoforms in 6-OHDA-induced death of PC12 cells. Twenty five µM 6-OHDA enhanced total JNK activity in the cytoplasm, nucleus, and at the mitochondria. Inhibition of JNKs by 2 µM SP600125 or transfection with dominant-negative JNK2 (dnJNK2) rescued more than 60% of the otherwise dying PC12 cells after 24 h, whereas transfection with dnJNK1 had no protective effects. In contrast to constitutively present JNK1, JNK2 amounts increased in the nucleus and at the mitochondria after 6-OHDA stimulation. JNK inhibition by SP600125 or transfection of dnJNK2 reduced the pool of active JNKs in the nucleus, the release of cytochrome c, as well as the cleavage of caspase-3 and its substrate poly(ADP-ribose) polymerase-1. Transfection with dnJNK1, however, had no effects on the translocation of JNKs to the mitochondria or the release of cytochrome c. Our data provide novel functional insights into the pathological role of individual JNK isoforms, the signalosome at the mitochondria, and the mode of JNK-induced release of cytochrome c.

Received for publication, May 26, 2004 , and in revised form, October 22, 2004.

^* This work was supported by the Deutsche Forschungsgemeinschaft Grants SFB 415 and SPP 1048. 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. Tel.: 49-431-597-3502; Fax: 49-431-597-3522; E-mail: herdegen.office{at}pharmakologie.uni-kiel.de.

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

This article has been cited by other articles:

				B. Bjorkblom, J. C. Vainio, V. Hongisto, T. Herdegen, M. J. Courtney, and E. T. Coffey All JNKs Can Kill, but Nuclear Localization Is Critical for Neuronal Death J. Biol. Chem., July 11, 2008; 283(28): 19704 - 19713. [Abstract] [Full Text] [PDF]

				M. M. Monick, L. S. Powers, C. W. Barrett, S. Hinde, A. Ashare, D. J. Groskreutz, T. Nyunoya, M. Coleman, D. R. Spitz, and G. W. Hunninghake Constitutive ERK MAPK Activity Regulates Macrophage ATP Production and Mitochondrial Integrity J. Immunol., June 1, 2008; 180(11): 7485 - 7496. [Abstract] [Full Text] [PDF]

				A. Takatori, E. Geh, L. Chen, L. Zhang, J. Meller, and Y. Xia Differential transmission of MEKK1 morphogenetic signals by JNK1 and JNK2 Development, January 1, 2008; 135(1): 23 - 32. [Abstract] [Full Text] [PDF]

				J. Pan, G. Wang, H.-Q. Yang, Z. Hong, Q. Xiao, R.-J. Ren, H.-Y. Zhou, L. Bai, and S.-D. Chen K252a Prevents Nigral Dopaminergic Cell Death Induced by 6-Hydroxydopamine through Inhibition of Both Mixed-Lineage Kinase 3/c-Jun NH2-Terminal Kinase 3 (JNK3) and Apoptosis-Inducing Kinase 1/JNK3 Signaling Pathways Mol. Pharmacol., December 1, 2007; 72(6): 1607 - 1618. [Abstract] [Full Text] [PDF]

				M. Wilhelm, Z. Xu, N. V. Kukekov, S. Gire, and L. A. Greene Proapoptotic Nix Activates the JNK Pathway by Interacting with POSH and Mediates Death in a Parkinson Disease Model J. Biol. Chem., January 12, 2007; 282(2): 1288 - 1295. [Abstract] [Full Text] [PDF]

				M. A. Bogoyevitch and B. Kobe Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1061 - 1095. [Abstract] [Full Text] [PDF]

				M. Nawaz, C. Manzl, V. Lacher, and G. Krumschnabel Copper-Induced Stimulation of Extracellular Signal-Regulated Kinase in Trout Hepatocytes: The Role of Reactive Oxygen Species, Ca2+, and Cell Energetics and the Impact of Extracellular Signal-Regulated Kinase Signaling on Apoptosis and Necrosis Toxicol. Sci., August 1, 2006; 92(2): 464 - 475. [Abstract] [Full Text] [PDF]

				E. M. Chalovich, J.-h. Zhu, J. Caltagarone, R. Bowser, and C. T. Chu Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal Cells J. Biol. Chem., June 30, 2006; 281(26): 17870 - 17881. [Abstract] [Full Text] [PDF]

				Y. Wang, R. Singh, J. H. Lefkowitch, R. M. Rigoli, and M. J. Czaja Tumor Necrosis Factor-induced Toxic Liver Injury Results from JNK2-dependent Activation of Caspase-8 and the Mitochondrial Death Pathway J. Biol. Chem., June 2, 2006; 281(22): 15258 - 15267. [Abstract] [Full Text] [PDF]

				K. Hanrott, L. Gudmunsen, M. J. O'Neill, and S. Wonnacott 6-Hydroxydopamine-induced Apoptosis Is Mediated via Extracellular Auto-oxidation and Caspase 3-dependent Activation of Protein Kinase C{delta} J. Biol. Chem., March 3, 2006; 281(9): 5373 - 5382. [Abstract] [Full Text] [PDF]

				C. Carlo-Stella, M. Di Nicola, M. C. Turco, L. Cleris, C. Lavazza, P. Longoni, M. Milanesi, M. Magni, M. Ammirante, A. Leone, et al. The Anti-Human Leukocyte Antigen-DR Monoclonal Antibody 1D09C3 Activates the Mitochondrial Cell Death Pathway and Exerts a Potent Antitumor Activity in Lymphoma-Bearing Nonobese Diabetic/Severe Combined Immunodeficient Mice Cancer Res., February 1, 2006; 66(3): 1799 - 1808. [Abstract] [Full Text] [PDF]

				J. Zhang, J. Liu, C. Yu, and A. Lin BAD Ser128 Is Not Phosphorylated by c-Jun NH2-Terminal Kinase for Promoting Apoptosis Cancer Res., September 15, 2005; 65(18): 8372 - 8378. [Abstract] [Full Text] [PDF]