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

J. Biol. Chem., Vol. 281, Issue 20, 14100-14110, May 19, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/20/14100    most recent M601820200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nelson, K. K. Articles by Melendez, J. A. Search for Related Content PubMed PubMed Citation Articles by Nelson, K. K. Articles by Melendez, J. A. Social Bookmarking                      What's this?

Redox-dependent Matrix Metalloproteinase-1 Expression Is Regulated by JNK through Ets and AP-1 Promoter Motifs^*

Kristin K. Nelson¹², Sita Subbaram¹, Kip M. Connor³, Jaya Dasgupta, Xiao-Fang Ha, Tzu-Ching Meng, Nicholas K. Tonks^¶, and J. Andres Melendez⁴

From the Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208, the Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, 105 Taipei, Taiwan, and ^¶Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

Reactive oxygen species have been shown to play an important role in the regulation of distinct signaling cascades, many of which act upon the production of matrix metalloproteinases (MMP). Using a series of redox-engineered cell lines we have previously demonstrated that MMP-1 expression is sensitive to the alterations in the steady state production of H₂O₂ (Ranganathan, A. C., Nelson, K. K., Rodriguez, A. M., Kim, K. H., Tower, G. B., Rutter, J. L., Brinckerhoff, C. E., Epstein, C. J., Huang, T. T., Jeffrey, J. J., and Melendez, J. A. (2001) J. Biol. Chem. 276, 14264–14270). In the present study, we investigate the molecular mechanisms involved in the H₂O₂-mediated induction of MMP-1. Mutational analysis of an MMP-1 promoter indicates that both the single nucleotide polymorphism creating an Ets binding site at –1607 and a proximal AP-1 site at –1602 are required for maximal H₂O₂-dependent transcription. The redox-sensitive MMP-1 protein expression requires activation of both ERK1/2 and JNK pathways. Importantly, JNK signaling is largely responsible for the H₂O₂ sensitivity of the MMP-1 promoter, whereas ERK1/2 contributes to both its basal and H₂O₂ dependence. H₂O₂ control of Ets-1 expression was ERK1/2-dependent whereas that of c-Jun requires both ERK1/2 and JNK signaling. Chromatin immunoprecipitation assays indicate that binding of the histone acetyltransferase, p300, and the transcription factors Ets-1 and c-Jun to the MMP-1 promoter is redox sensitive. The redox sensitivity of MMP-1 expression is also associated with an increase in the abundance of oxidatively inactivated protein-tyrosine phosphatases. Targeted cytosolic or mitochondrial scavenging of H₂O₂ prevented all of the aforementioned signals. These studies provide substantial insight into the mechanisms underlying the redox-dependent control of MMP-1 and may lead to the development of novel targeted antioxidant-based inhibitory therapies for controlling MMP-1 expression during degenerative disease processes.

Received for publication, February 24, 2006

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

^* This work was supported, in part, by Philip Morris USA, Inc. and Philip Morris International and Public Health Service Grants CA77068 and CA095011 (to J. A. M.), GM55989 (to N. K. T.), and National Institutes of Health Predoctoral Fellowship AI49822 (to K. K. N. and K. M. C.). 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.

¹ Both authors contributed equally to this work.

² Present address: James Graham Brown Cancer Center, Baxter II Biomedical Research Bldg., University of Louisville, 580 South Preston St., Louisville, KY 40202.

³ Present address: Dept. of Opthalmalogy, Karp Family Research Bldg., RB11004g, 1 Blackfan Cir., Boston, MA 02115.

⁴ To whom correspondence should be addressed: Center for Immunology and Microbial Disease, MC 151, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208. Fax: 518-262-6161; E-mail: melenda{at}mail.amc.edu.

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

This article has been cited by other articles:

				I. T. Struewing, S. N. Durham, C. D. Barnett, and C. D. Mao Enhanced Endothelial Cell Senescence by Lithium-induced Matrix Metalloproteinase-1 Expression J. Biol. Chem., June 26, 2009; 284(26): 17595 - 17606. [Abstract] [Full Text] [PDF]

				J. Lai, S. A. Myers, M. G. Lawrence, D. M. Odorico, and J. A. Clements Direct Progesterone Receptor and Indirect Androgen Receptor Interactions with the Kallikrein-Related Peptidase 4 Gene Promoter in Breast and Prostate Cancer Mol. Cancer Res., January 1, 2009; 7(1): 129 - 141. [Abstract] [Full Text] [PDF]

				W. Ni, Y. Zhan, H. He, E. Maynard, J. A. Balschi, and P. Oettgen Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47phox Gene Expression in Response to Angiotensin II Circ. Res., November 9, 2007; 101(10): 985 - 994. [Abstract] [Full Text] [PDF]

				K. M. Connor, N. Hempel, K. K. Nelson, G. Dabiri, A. Gamarra, J. Belarmino, L. Van De Water, B. M. Mian, and J. A. Melendez Manganese Superoxide Dismutase Enhances the Invasive and Migratory Activity of Tumor Cells Cancer Res., November 1, 2007; 67(21): 10260 - 10267. [Abstract] [Full Text] [PDF]

				K. S. Mix, M. G. Attur, H. Al-Mussawir, S. B. Abramson, C. E. Brinckerhoff, and E. P. Murphy Transcriptional Repression of Matrix Metalloproteinase Gene Expression by the Orphan Nuclear Receptor NURR1 in Cartilage J. Biol. Chem., March 30, 2007; 282(13): 9492 - 9504. [Abstract] [Full Text] [PDF]