QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Ogita, K. Articles by Yoneda, Y. Search for Related Content PubMed PubMed Citation Articles by Ogita, K. Articles by Yoneda, Y.

 Previous Article  |  Next Article 

The Journal of Neuroscience, April 1, 2002, 22(7):2561-2570

Localization of Activator Protein-1 Complex with DNA Binding Activity in Mitochondria of Murine Brain after In Vivo Treatment with Kainate

Kiyokazu Ogita¹, Hiroaki Okuda¹, Masahiro Kitano¹, Yoshiaki Fujinami¹, Kiyokazu Ozaki², and Yukio Yoneda³

¹ Department of Pharmacology, ² Research Institute of Drug Safety, Setsunan University Faculty of Pharmaceutical Sciences, Hirakata, Osaka 573-0101, Japan, and ³ Department of Molecular Pharmacology, Kanazawa University Faculty of Pharmaceutical Sciences, Kanazawa, Ishikawa 920-0934, Japan

To elucidate mechanisms underlying mitochondrial dysfunctions induced by glutamate, we have examined the effects of in vivo treatment with the ionotropic glutamate receptor agonist kainate on localization of the transcription factor activator protein-1 (AP-1) in mitochondria as well as nuclei of murine brain. A systemic administration of kainate dramatically enhanced AP-1 DNA binding in both mitochondrial and nuclear extracts of mouse cerebral cortex and hippocampus 1 hr to 3 d later. Unlabeled AP-1 probe selectively competed for AP-1 DNA binding in mitochondrial extracts of cortex and hippocampus obtained from mice injected with kainate. Supershift and immunoblotting analyses revealed participation of c-Fos, Fos-B, and Jun-B proteins in potentiation by kainate of mitochondrial AP-1 DNA binding in cortex and hippocampus. An immunohistochemical study demonstrated marked expression by kainate of c-Fos protein in the pyramidal and dentate granular layers, whereas an immunoelectron microscopic analysis showed localization of c-Fos protein within mitochondria, as well as nuclei, of the CA1 pyramidal and dentate granular cells in hippocampus obtained 2 hr after the administration of kainate. Mitochondrial AP-1 DNA binding was inhibited by particular unlabeled oligonucleotides containing sequences similar to the AP-1 site found in the noncoding region of mitochondrial DNA. Kainate markedly potentiated binding of radiolabeled oligonucleotide probes containing sequences effective in competing for AP-1 DNA binding in hippocampal mitochondrial extracts. These results suggest that kainate may facilitate expression of the AP-1 complex and subsequent translocation into mitochondria to participate in mechanisms associated with transcriptional regulation of mitochondrial DNA in murine hippocampus.

Key words: activator protein-1; DNA binding; c-Fos protein; kainate; mitochondria; mitochondrial DNA

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/2272561-10$05.00/0

This article has been cited by other articles:

				N. V. Guseva, A. F. Taghiyev, M. T. Sturm, O. W. Rokhlin, and M. B. Cohen Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated Activation of Mitochondria-Associated Nuclear Factor-{kappa}B in Prostatic Carcinoma Cell Lines Mol. Cancer Res., October 1, 2004; 2(10): 574 - 584. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help